Occupational, academic, and personal determinants of wellbeing and psychological distress in residents: results of a survey in Lyon, France.

Introduction: The mental health of residents is a growing significant concern, particularly with respect to hospital and university training conditions. Our goal was to assess the professional, academic, and psychological determinants of the mental health status of all residents of the academy of Lyon, France. Materials and methods: The Health Barometer of Lyon Subdivision Residents (BASIL) is an initiative which consists in proposing a recurrent online survey to all residents in medicine, pharmacy, and dentistry, belonging to the Lyon subdivision. The first of these surveys was conducted from May to July 2022. Participants should complete a series of validated questionnaires, including the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), and the Kessler Psychological Distress Scale (K6), respectively, and ad-hoc questions assessing their global health and hospital and academic working conditions. A Directed Acyclic Graph (DAG) analysis was conducted prior to multivariable analyses, to explore the determinants associated with low wellbeing (WEMWBS <43) and high psychological distress (K6 ≥ 13). Results: A total of 904 residents (response rate: 46.7%) participated in the survey. A low level of wellbeing was observed in 23% of participants, and was significantly associated to job strain (OR = 2.18; 95%CI = [1.32-3.60]), low social support (OR = 3.13; 95%CI = [2.05-4.78]) and the experience of very poor university teaching (OR = 2.51; 95%CI = [1.29-4.91]). A high level of psychological distress was identified for 13% of participants, and associated with low social support (OR = 2.41; 95%CI = [1.48-3.93]) and the experience of very poor university teaching (OR = 2.89, 95%CI = [1.16-7.21]). Conclusion: Hospital working conditions, social support, and the perception of teaching quality, were three major determinants of wellbeing and psychological distress among health profession residents. Demographic determinants, personal life and lifestyle habits were also associated. This supports a multilevel action in prevention programs aiming to enhance wellbeing and reduce mental distress in this specific population and local organizational specificities.

Implementing Indicators and Trajectories of Return to Work After Breast Cancer Diagnosis: A Mixed-Methods Study Using the French National Healthcare Insurance Database and Stakeholder Consultation.

PURPOSE: Return to work (RTW) is important for quality of life after breast cancer but its analysis at the population-level remains limited in France. This study aimed to implement Electronic Healthcare Data (EHD)-based indicators and trajectories to measure RTW after breast cancer diagnosis, and to examine stakeholders' perspectives regarding these indicators. METHODS: We followed a mixed-methods approach that consisted of (i) implementing RTW indicators and identifying clusters of trajectories using state sequence analysis with data from a representative sample of the French National Health Data System and (ii) exploring, through qualitative focus group and interviews, stakeholders' perceptions on the interpretation, limitations, and utility of these indicators. RESULTS: We extracted data from 317 women aged 25-55 years with a first diagnosis of early-stage breast cancer. The median number of sickness absence periods was 2 for a total of 434 days during the 3-year follow-up, and the median time to sustainable RTW was 240 days. Three clusters of RTW trajectories were identified: "early RTW" (49.5% of the population), "RTW after partial resumption" (37.5%) and "continuous compensation" (12.9%). Feedback from stakeholders highlighted the multi-factorial nature of RTW and underscored the added value of EHD for studying RTW, despite certain limitations. CONCLUSIONS: We demonstrated the feasibility of calculating RTW indicators and identifying trajectories using the French National Health Data System. These indicators can serve as outcome measures in RTW promotion and provide a basis for designing targeted interventions for breast cancer survivors.

Combining SARS-CoV-2 interferon-gamma release assay with humoral response assessment to define immune memory profiles.

OBJECTIVES: In the post-SARS-CoV-2 pandemic era, "breakthrough infections" are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti-Spike (S) immunoglobulin-G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T-cell response assessment to enhance the definition of immune memory profile. METHODS: SARS-CoV-2 interferon-gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti-receptor-binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated. RESULTS: Close to 40% of our samples were exclusively IGRA-positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long-lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti-receptor-binding domain IgG and IGRA levels tended to reduce it. CONCLUSION: The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level.

Planning Individual and Population-Based Interventions in Global Health: Applying the DEA-A Framework to Promote Behavioral, Emotional, and/or Cognitive Change among Stakeholders.

Addressing health challenges that impact human well-being requires a comprehensive, interdisciplinary approach that would be at the crossroad of population-based prevention and individual-level clinical care, which is in line with a Global Health perspective. In the absence of a unifying theoretical framework to guide such interventions, a Dynamic Ecosystem Adaptation through the Allostasis (DEA-A) framework has been proposed, emphasizing the functional adaptation of individuals and organizations in symbiosis with their living ecosystem. While a conceptual model has been presented, this methodological contribution aims at illustrating the practical application of the DEA-A framework for planning Global Health interventions. The methodology combines Intervention Mapping and Cognitive and Behavioral Theory, extended to the ecosystem. Practical guidelines and supporting tools are provided to help public health providers and clinicians in establishing a functional ecosystem diagnosis of the issue; defining not only behavioral, but also emotional and cognitive change objectives (allostasis targets) expected for each stakeholder; and designing intervention plans targeting determinants of these allostasis. The discussion addresses implementation and evaluation perspectives of interventions based on the DEA-A framework, emphasizing the importance of considering change in its processual and ecosystem complexity. Lastly, encouragements for a deeper understanding of individual and ecosystem homeostasis/allostasis processes are made in order to promote more functional interventions.

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.

A third vaccine dose equalises the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens, Lyon, France, December 2021 to March 2022.

BackgroundTo cope with the persistence of the COVID-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.AimWe wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.MethodsWe combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse immunological parameters before and after the third mRNA vaccine dose.ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18-3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72-1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.ConclusionThe advantage conferred by heterologous vaccination was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Prior SARS-CoV-2 infection enhances and reshapes spike protein-specific memory induced by vaccination.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Laws, Policies, and Collective Agreements Protecting Low-wage and Digital Platform Workers During the COVID-19 Pandemic.

In the context of the COVID-19 pandemic, this commentary describes and compares shifting employment and occupational health social protections of low-wage workers, including self-employed digital platform workers. Through a focus on eight advanced economy countries, this paper identifies how employment misclassification and definitions of employees were handled in law and policy. Debates about minimum wage and occupational health and safety standards as they relate to worker well-being are considered. Finally, we discuss promising changes introduced during the COVID-19 pandemic that protect the health of low-wage and self-employed workers. Overall, we describe an ongoing "haves" and a "have not" divide, with on the one extreme, traditional job arrangements with good work-and-health social protections and, on the other extreme, low-wage and self-employed digital platform workers who are mostly left out of schemes. However, during the pandemic small and often temporary gains occurred and are discussed.

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.

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.

[French translation and adaptation of the "Return to Work Self-Efficacy' Scale - 11 items" in patients diagnosed with a cancer]. / Traduction et adaptation française du « Return to Work Self-Efficacy' scale ­ 11 items ¼ chez des patients diagnostiqués d'un cancer.

INTRODUCTION: The self-efficacy to return to work is a major psychological factor of the return to work of patients diagnosed with a cancer. However, french investigations in this field do not take this dimension into account due to the lack of a suitable tool for its assessment. The objective of this study was to provide a french translation and adaptation of the "Return to Work Self-Efficacy' scale - 11 items" (RTWSE-11), validated in dutch language in its original version. METHODS: After translation-back translation steps, completed by experts' consensus meetings, interviews were conducted with thirteen patients diagnosed with cancer in order to evaluate the degree of clarity, simplicity and ambiguity or the various elements of the french version of the RTW-SE-11. RESULTS: The main modifications inherent to the french adaptation of the questionnaire concerned the modalities of the Likert scale and the inversion of three negative items into positive items. DISCUSSION: The french translation and adaptation of the RTWSE-11 was particularly faithful to the semantic, idiomatic, functional, experiential, conceptual and operational aspects of the original version. Future work can therefore focus on the psychometrics evaluations of the questionnaire. However, this tool can already be used in clinical practice to establish an initial assessment of the ability of patients diagnosed with cancer to return to work.

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.

Connected device and therapeutic patient education to promote physical activity among women with localised breast cancer (DISCO trial): protocol for a multicentre 2×2 factorial randomised controlled trial.

INTRODUCTION: Despite safety and benefits of physical activity during treatment of localised breast cancer, successful exercise strategies remain to be determined. The primary objective of the 'dispositif connecté', that is, connected device in English trial is to evaluate the efficacy of two 6-month exercise interventions, either single or combined, concomitant to adjuvant treatments, on the physical activity level of patients with breast cancer, compared with usual care: an exercise programme using a connected device (activity tracker, smartphone application, website) and a therapeutic patient education intervention. Secondary objectives are to evaluate adherence to interventions, their impact at 6 and 12 months, representations and acceptability of interventions, and to assess the cost-effectiveness of the interventions using quality-adjusted life-years. METHODS AND ANALYSIS: This is a 2×2 factorial, multicentre, phase III randomised controlled trial. The study population (with written informed consent) will consist of 432 women diagnosed with primary localised invasive breast carcinoma and eligible for adjuvant chemotherapy, hormonotherapy and/or radiotherapy. They will be randomly allocated between one of four arms: (1) web-based connected device (evolving target number of daily steps and an individualised, semisupervised, adaptive programme of two walking and one muscle strengthening sessions per week in autonomy), (2) therapeutic patient education (one educational diagnosis, two collective educational sessions, one evaluation), (3) combination of both interventions and (4) control. All participants will receive the international physical activity recommendations. Assessments (baseline, 6 and 12 months) will include physical fitness tests, anthropometrics measures, body composition (CT scan, bioelectrical impedance), self-administered questionnaires (physical activity profile (Recent Physical Activity Questionnaire), quality of life (European Organization for Research and Treatment of Cancer Quality-Of-Life Questionnaire-30, EQ-5D-5L), fatigue (Piper Fatigue Scale-12), social deprivation (Evaluation of Deprivation and Inequalities in Health Examination Centres), lifestyle, physical activity barriers, occupational status) and biological parameters (blood draw). ETHICS AND DISSEMINATION: This study was reviewed and approved by the French Ethics Committee. The findings will be disseminated to the scientific and medical community via publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT03529383; Pre-results.

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.