Outcome of the Compensation Process Initiated by an Occupational and Environmental Diseases Center.

BACKGROUND: Regional Centers for Occupational and Environmental Pathologies (CRPPE) are responsible for identifying possible occupational etiologies of pathologies. When an occupational origin is determined, an Initial Medical Certificate (IMC) is given to the patient to allow him to initiate a procedure for recognition as an occupational disease (OD) by his health insurance organization. OBJECTIVES: The main aim of this study was to investigate the outcome of occupational disease claims in patients who received an IMC delivered by the CRPPE of Lyon. METHODS: A telephone interview was systematically conducted with patients who consulted the CRPPE for a claim for occupational disease recognition between 07/2020 and 06/2021, about six months after the consultation. It was conducted by a physician using a standardized questionnaire. RESULTS: Out of 128 patients eligible for this study, 98 were included. Diseases of the respiratory system (34.7%) and cancers (28.6%) were the most common pathologies in our population. A process of OD compensation was initiated by 86 patients (87.8%). At the time of the study, the outcome was favorable for 63 patients (73.3%). Moreover, 18 patients (18.4%) wished for additional help from the CRPPE to carry out the procedures. Nine patients requested a new consultation, including five who still needed to complete the process. CONCLUSION: This study shows the benefit of a consultation by occupational disease consultants. However, difficulties still need to be solved in these procedures. Thus, the systematic follow-up of patients shows its advantages. The provision of support to carry out the process seems necessary.

Underreporting of occupational blood and body fluid exposure in French university hospitals in 2017.

BACKGROUND: Occupational blood and body fluid exposures (OBBFEs) are one of the biological risks run by health professionals, especially in hospitals. OBJECTIVE: The objectives of this study were to assess the occurrence and reporting of occupational blood and body fluid exposures (OBBFEs) in university hospital medical staff and to investigate factors associated to declared OBBFE and factors associated to reported OBBFE. METHODS: A self-administered questionnaire has been e-mailed to all junior and senior medical staff in four university hospital centers in one administrative region of France in 2017. RESULTS: 292 of the 1,228 respondents declared at least one OBBFE. More than two-thirds (70.2%) were under-reporters and more than half (53.8%) non-reporters. Younger subjects, surgical specialties and other associated work accidents were risk factors for OBBFE. Considering the reporting procedure too complex was a risk factor for underreporting. CONCLUSIONS: Underreporting by hospital medical staff was a persistent phenomenon, with a high rate. The OBBFE reporting procedure needs rethinking.

COVID-19 clusters in a teaching hospital during the second wave of the SARS-CoV-2 pandemic in France: A descriptive study and lessons learned for waves to come.

A total of 92 coronavirus disease 2019 clusters involving 1,156 individuals (729 patients and 427 healthcare workers) occurred in Lyon University Hospital between September 1, 2020 and March 31, 2021, mostly on medical and geriatric wards. The number of clusters was closely correlated to the trend in coronavirus disease 2019 community incidence over time; in-hospital clusters did not persist when community incidence decreased. Recommended preventive measures were not fully applicable due to specific ward-associated determinants and patient characteristics.

Evaluation of commercial Anti-SARS-CoV-2 neutralizing antibody assays in seropositive subjects.

The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.

Exposure of paediatric healthcare personnel to nitrous oxide in paediatric care units.

Nitrous oxide (N2O) was found responsible for genetic and reproductive toxicities, whereas it is widely used in paediatric care units where most healthcare providers are women of childbearing age. This motivated investigating occupational overexposure and overexposure factors in several paediatric hospital units. A cross-sectional study was carried out in seven healthcare units. On each of 34 healthcare providers, air samples were extracted (portable pumps and Tedlar® bags) and N2O quantified (gas chromatography, pulsed discharge ionization detection, and infrared spectrometry). The data allowed calculating mean instantaneous exposures. The mean instantaneous exposure was: i) four times higher in closed vs. open treatment rooms; ii) two times higher in case of use vs. non-use of N2O; iii) significantly higher in junior vs. senior healthcare providers (by 12%); and, iv) higher during presumably short vs. presumably long procedures (by 20%). Overexposures to N2O were mainly seen in the emergency unit and in day hospitals for thoracic/abdominal diseases and nephrology. Overexposures were frequent during short-duration procedures; among 88 N2O measurements, 77 (87.5%) exceeded the 200 ppm threshold over 15 minutes. The overexposures call for dedicated treatment rooms (with adequate equipment and ventilation), more efficient anaesthetic practices, appropriate training, and regular checks.

Evaluation of Commercial Anti-SARS-CoV-2 Antibody Assays and Comparison of Standardized Titers in Vaccinated Health Care Workers.

With the availability of vaccines, commercial assays detecting anti-severe acute respiratory syndrome coronavirus-2 antibodies (Ab) evolved toward quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after one dose (convalescent individuals) or two doses (naive individuals) of vaccine, in health care workers (HCW). Antibody titers were measured in 255 sera (from 150 HCW) with five quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti-RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization internal standard. There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/mL correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens. A true standardization of the assays would be to include the International Standard in the calibration of each assay to express the results in IU/mL.

Immunogenicity and efficacy of          heterologous ChAdOx1-BNT162b2 vaccination.

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.

Specific detection of memory T-cells in COVID-19 patients using standardized whole-blood Interferon gammarelease assay.

Antigen-specific T-cells are essential for protective immunity against SARS-CoV-2. We set up a semi-automated whole-blood Interferon-gamma release assay (WB IGRA) to monitor the T-cell response after stimulation with SARS-CoV-2 peptide pools. We report that the WB IGRA is complementary to serological assays to assess SARS-CoV-2 immunity.

Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study.

A comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs (p = 0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/mL (Ct value < 25) was less than 15% at 8 days after symptom onset; 12% of HCWs were positive after 40 days (Ct > 37). More than 90% of cultivable virus had a viral load > 4.5 log10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work.

Radio-frequency electromagnetic field exposure and contribution of sources in the general population: an organ-specific integrative exposure assessment.

In order to achieve an integrated radio-frequency electromagnetic fields (RF-EMF) dose assessment, detailed information about source-specific exposure duration and output power is needed. We developed an Integrated Exposure Model (IEM) to combine energy absorbed due to use of and exposure to RF-EMF sources and applied it to a sample of the general population to derive population RF-EMF estimates. The IEM used specific absorption rate transfer algorithms to provide RF-EMF daily dose estimates (mJ/kg/day) using source-specific attributes (e.g. output power, distance), personal characteristics and usage patterns. Information was obtained from an international survey performed in four European countries with 1755 participants. We obtained median whole-body and whole-brain doses of 183.7 and 204.4 mJ/kg/day. Main contributors to whole-brain dose were mobile phone near the head for calling (2G networks) and far-field sources, whereas the latter together with multiple other RF-EMF sources were main contributors for whole-body dose. For other anatomical sites, 2G phone calls, mobile data and far-field exposure were important contributors. The IEM provides insight into main contributors to total RF-EMF dose and, applied to an international survey, provides an estimate of population RF-dose. The IEM can be used in future epidemiological studies, risk assessments and exposure reduction strategies.

Evaluation of High-Throughput SARS-CoV-2 Serological Assays in a Longitudinal Cohort of Patients with Mild COVID-19: Clinical Sensitivity, Specificity, and Association with Virus Neutralization Test.

BACKGROUND: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19. METHODS: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of 9 commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement, and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers. RESULTS: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3% (78.1-96.1), and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG, and DiaSorin, respectively. None of the commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC < 0.76). CONCLUSIONS: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests, including those targeting the RBD, cannot substitute a VNT for the assessment of functional antibody response.

Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study.

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.

Assessment of Personal Occupational Exposure to Radiofrequency Electromagnetic Fields in Libraries and Media Libraries, Using Calibrated On-Body Exposimeters.

BACKGROUND AND OBJECTIVES: With the spread of Wifi networks, safety concerns have arisen, with complaints of somatic disorders, notably in traditional libraries and media libraries. The aim of the present study was to describe the conditions and levels of exposure to radiofrequency electromagnetic fields in the real-life occupational conditions of those working in traditional libraries and media libraries. METHODS: Dynamic measurements, using an exposimeter, were taken in 20 radiofrequency bands from 88 to 5850 MHz. The activity of 28 library workers was analyzed on a space-time budget. An audit of exposure sources and static measurements enabled the work-places to be mapped. RESULTS: In seven libraries, 78,858 samples were taken over the 20 radiofrequency bands from 88 to 5850 MHz. Exposure was described for 28 working days. The median total field was 0.071 V/m (10th percentile: 0.022 V/m, 90th percentile: 0.534 V/m) and for Wifi the median field was 0.005 V/m (10th percentile: 0.005 V/m, 90th percentile: 0.028 V/m). Median individual exposure to Wifi frequency waves ranged from 0.005 to 0.040 V/m. CONCLUSIONS: Overall, the occupational exposure in this sector was close to the exposure in the general population. Peaks were due to the use of walkie-talkies by security staff. Exposure due to external sources depended on geographic location. Exposure in this occupation is well below the general occupational exposure levels, notably as regards Wifi.

Validation of self-reported occupational noise exposure in participants of a French case-control study on acoustic neuroma.

OBJECTIVES: To validate self-reported occupational loud noise exposure against expert evaluation of noise levels in a French case-control study on acoustic neuroma and to estimate the impact of exposure misclassification on risk estimation. METHODS: Noise levels were evaluated in 1006 jobs held by 111 cases and 217 population controls by an expert. Case-control differences in self-reporting were analyzed with logistic models. Sensitivity, specificity, positive and negative predictive values, and observed agreement of the self-reports were computed relative to the expert evaluation. They were used to calibrate the odds ratio (OR) between lifetime ever occupational loud noise exposure and the risk of acoustic neuroma, without adjustment for measurement error of the expert assessments. RESULTS: Cases reported noise levels in individual jobs closer to the expert assessment than controls, but the case-control difference was small for lifetime exposures. For expert-rated exposure of 80 dB(A), reporting of individual jobs by cases was more sensitive (54% in cases, 37% in controls), whereas specificity (91% in cases, 93% in controls) and observed agreement (82% in cases, 81% in controls) were similar. When lifetime exposure was considered, sensitivity increased (76% in cases, 65% in controls), while cases specificity decreased (84%). When these values were used to calibrate self-reports for exposure misclassification compared to expert evaluation at 80 dB(A), the crude OR of 1.7 was reduced to 1.3. CONCLUSIONS: Despite the relatively accurate reporting of loud noise, the impact of the calibration on the OR was non-negligible.

Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study.

Objective Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000-2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. Methods Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. Results The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4-1.9). OR were 1.5 (95% CI 1.3-1.9) for only occupational noise, 1.9 (95% CI 1.4-2.6) for only leisure noise and 1.7 (95% CI 1.2-2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. Conclusion The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.

Systematic screening for occupations and occupational exposures in head and neck squamous cell carcinoma patients.

PURPOSE: The importance of occupational exposures in patients with head and neck squamous cell carcinomas (HNSCC) has received little attention. METHODS: In a single-center study, we prospectively characterized occupational exposures in 154 HNSCC cancer patients in a systematic occupational consultation and examined the association between most frequent exposures, HNSCC stage and localization. RESULTS: Patients occupied a mean of 3.3 different positions during their working life. The prevalence of asbestos, the most frequent exposure (46 patients; 29.9%) was higher than in the French population > 50 years. Other frequent exposures were solvents (n = 26; 16.9%) and silica (n = 19; 12.3%). For 37 patients (24%) a possible link was identified between occupational exposures and HNSCC. Duration of asbestos exposure was significantly higher (p = 0.04) in patients with hypopharyngeal and laryngeal cancer compared to other localizations. CONCLUSIONS: Occupational exposures are frequent in patients with HNSCC and should receive increased attention by physicians.

[Assessment of a self-administered questionnaire identifying occupational exposures among lung cancer patients]. / Évaluation d'un auto-questionnaire de repérage des expositions professionnelles chez les patients atteints de cancer bronchopulmonaire.

Ten to 29% of lung cancers might be linked to occupational factors but 60% of them are not compensated. The PROPOUMON project aimed to improve the identification, recognition and compensation of occupational lung cancer as occupational disease using a self-administered questionnaire (AQREP). One objective was to assess the AQREP, comparing it with the questionnaire drawn up by the French Language Pneumology Society (Q-SPLF). From March 2014 to September 2015, 90 lung cancer patients treated at the Centre Léon-Bérard responded to the AQREP and Q-SPLF. The two physicians in charge of the consultation assessed independently whether or not a consultation was indicated. A certificate for the compensation process was proposed when a suspicion of high or average imputability was identified. Analysis of the questionnaires was concordant for 73% of the patients. The AQREP has a sensitivity of 72% and a specificity of 73%. Its positive and negative predictive values were 62 and 82%. The information provided by 24 patients were discordant between questionnaires. In two patients with discordant evaluation (AQREP+/Q-SPLF-; AQREP-/Q-SPLF+), one Initial Medical Certificate (IMC) was written. This study made it possible to conclude that AQREP is relevant for the identification of potentially occupational lung cancers. Collegial discussion of complex cases might be considered. The project is currently been extended to other centers and to lymphoma.

Using software-modified smartphones to validate self-reported mobile phone use in young people: A pilot study.

A newly developed smartphone application was piloted to characterize and validate mobile phone use in young people. Twenty-six volunteers (mean age 17.3 years) from France, Spain, and the Netherlands used a software-modified smartphone for 4 weeks; the application installed on the phone recorded number and duration of calls, data use, laterality, hands-free device usage, and communication system used for both voice calls and data transfer. Upon returning the phone, participants estimated their mobile phone use during those 4 weeks via an interviewer-administered questionnaire. Results indicated that participants on average underestimated the number of calls they made, while they overestimated total call duration. Participants held the phone for about 90% of total call time near the head, mainly on the side of the head they reported as dominant. Some limitations were encountered when comparing reported and recorded data use and speaker use. When applied in a larger sample, information recorded by the smartphone application will be very useful to improve radiofrequency (RF) exposure modeling from mobile phones to be used in epidemiological research.