High-Resolution 1.5-Tesla Magnetic Resonance Imaging for Tissue-Engineered Constructs: A Noninvasive Tool to Assess Three-Dimensional Scaffold Architecture and Cell Seeding

International audienceTissue-engineered scaffolds are made of biocompatible polymers with various structures, allowing cell seeding, growth, and differentiation. Noninvasive imaging methods are needed to study tissue-engineered constructs before and after implantation. Here, we show that high-resolution magnetic resonance imaging (MRI) performed on a clinical 1.5-T device is a reliable technique to assess three-dimensional structures of porous scaffolds and to validate cell-seeding procedures. A high-temperature superconducting detection coil was used to achieve a resolution of 30Â30Â30 mm 3 when imaging the scaffolds. Three types of structures with tuneable architectures were prepared from naturally derived polysaccharides and evaluated as scaffolds for mesenchymal stem cell (MSC) culture. To monitor cell seeding, MSCs were magnetically labeled using simple incubation with anionic citrate-coated iron-oxide nanoparticles for 30 min. Iron uptake was quantified using single-cell magnetophoresis, and cell proliferation was checked for 7 days after labeling. Three-dimensional (3D) microstructures of scaffolds were assessed using MRI, revealing lamellar or globular porous organization according to the scaffold preparation process. MSCs with different iron load (5, 12 and 31 pg of iron per cell) were seeded on scaffolds at low density (132 cells=mm 3) and detected on 3D gradient-echo MR images according to phase distortions and areas of intensely low signal, whose size increased with cell iron load and echo time. Overall signal loss in the scaffold correlated with the number of seeded cells and their iron load. Different organizations of cells were observed depending on the scaffold architecture. After subcutaneous implantation in mice, scaffolds seeded with labeled cells could be distinguished in vivo from scaffold with nonlabeled cells by observation of signal and phase heterogeneities and by measuring the global signal loss. High-resolution 1.5-T MRI combined with efficient intracellular contrast agents shows promise for noninvasive 3D visualization of tissue-engineered constructs before and after in vivo implantation

Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England.

BACKGROUND: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. METHODS: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts' vaccination status as the main exposure while adjusting for confounders. RESULTS: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35-0.72) and 0.69 (0.53-0.90) for receipt of two doses 8-90 and >90 days ago, respectively, and 0.34 (0.23-0.50) for vaccination with three doses 8-151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts' infection risk: 0.45 (0.23-0.89). CONCLUSIONS: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose

End of 2022/23 season influenza vaccine effectiveness in primary care in Great Britain

Background The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2–13 (and 14–15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. Methods End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: −6% to 54%). VE for those aged 18–64, who largely received cell-based vaccines, was 47% (95% CI: 37%–56%). Overall VE for 2–17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%–76%). Conclusion The paper provides evidence of moderate influenza VE in 2022/23

Epidemiology of work-related asthma : assessment of occupational exposures and their association with the disease

Actuellement, l’asthme est la 1ère maladie professionnelle respiratoire. L’utilisation de produits de nettoyage et de désinfection est un facteur de risque émergent de l’asthme lié au travail, surtout dans le secteur de la santé. Cependant, les produits spécifiques en cause dans l’asthme restent à identifier. L’évaluation de l’exposition professionnelle aux produits de nettoyage et de désinfection est difficile dans les études épidémiologiques. De plus, le biais du travailleur sain (HWE) est important à considérer dans les études épidémiologiques sur l’asthme lié au travail.L’objectif de la thèse comportait deux aspects : 1) un aspect méthodologique visant à améliorer l’évaluation des expositions professionnelles aux produits de nettoyage et de désinfection en développant des méthodes novatrices ; 2) un aspect étiologique visant à estimer le rôle des expositions professionnelles dans le contrôle de l’asthme en prenant en compte un potentiel HWE.Tout d’abord, des matrices emplois-expositions (MEE) et emplois-tâches¬-expositions (METE) ont été développées via les données de femmes non-asthmatiques tirées au sort dans une cohorte prospective d’infirmières américaine (NHSII : Nurse’s Health Study II). Puis, une méthode d’évaluation des expositions professionnelles aux produits de nettoyage et de désinfection utilisant une application smartphone scannant les codes-barres de produits et une base de données (BDD) a été développée. L’étude du rôle des expositions professionnelles aux produits de nettoyage et de désinfection dans le contrôle de l’asthme a été réalisée dans l’étude Épidémiologique des facteurs Génétiques et Environnementaux de l'Asthme disposant de données longitudinales détaillées sur l’histoire professionnelle et les phénotypes d’asthme. Afin de prendre en compte un potentiel HWE, un modèle marginal structural (MMS) a été appliqué.Une hétérogénéité de l’estimation des expositions par les MEE et METE était observée dans la plupart des métiers infirmiers, sauf pour les infirmières exerçant aux urgences et dans l’administration/la formation. Nous avons montré que la METE était plus adaptée que la MEE pour estimer les expositions, en particulier pour les métiers infirmiers ayant des tâches hétérogènes. Via l’application, 126 produits ont été recueillis auprès de 14 personnels hospitaliers de l’étude pilote, et des informations sur les composés étaient disponibles pour tous les produits via la BDD associée. Cette étude a montré que ce nouvel outil était simple à mettre en place, facile et rapide à utiliser pour les participants, et permettait d’évaluer de façon précise les expositions aux différentes substances. Ces résultats confirment la faisabilité et l’intérêt de cette méthode et suggèrent son déploiement dans les études épidémiologiques. Dans la partie étiologique, nous avons observé la présence d’un HWE dans notre échantillon d’étude. Malgré la prise en compte de ce HWE en utilisant un MMS, les résultats des associations ne permettaient pas de conclure sur le rôle des expositions professionnelles dans le contrôle de l’asthme.Currently, asthma is the first occupational respiratory disease. The use of disinfectants and cleaning products has been identified as an emerging risk factor for work-related asthma, especially in the healthcare industry. However, identifying the specific products at risk for asthma remains challenging, partly because assessment of occupational exposure to disinfectants/cleaning products is difficult in epidemiological studies and needs improvement. Moreover, taking into account possible healthy worker effect (HWE) is essential in work-related asthma study.The aims of the thesis were to improve the methods for assessment of occupational exposure to disinfectants/cleaning products by developing new methods; and to study the association between occupational exposure to disinfectants/cleaning products and asthma control taking into account a possible HWE.First, job-exposure (JEM) and job-task-exposure matrices (JTEM) have been created using data from a random sample of women without asthma from a large prospective cohort of US nurses (NHSII: Nurse’s Health Study II). Second a new assessment method using a smartphone application with a barcode scanner and a database was designed to evaluate occupational exposure to disinfectants and cleaning products. The study of the association between occupational exposure to disinfectants and cleaning products and asthma control has used data from the French Epidemiological study on the genetics and environment of asthma. Longitudinal data were available on occupational history and asthma phenotypes. To control for a possible HWE, a marginal structural model (MSM) was used.For the first part, JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration. The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Through the smartphone application, 126 products were registered for 14 hospital workers of the pilot study. Information on components was available for all products in the database. The method developed is feasible and applicable to larger epidemiological studies. In the etiological part, a HWE was observed in the study sample. Even after controlling for a HWE, results did not allow concluding on the association between occupational exposures and control of asthma

Épidémiologie de l'asthme lié au travail : évaluation des expositions professionnelles et leurs associations avec la maladie

Currently, asthma is the first occupational respiratory disease. The use of disinfectants and cleaning products has been identified as an emerging risk factor for work-related asthma, especially in the healthcare industry. However, identifying the specific products at risk for asthma remains challenging, partly because assessment of occupational exposure to disinfectants/cleaning products is difficult in epidemiological studies and needs improvement. Moreover, taking into account possible healthy worker effect (HWE) is essential in work-related asthma study.The aims of the thesis were to improve the methods for assessment of occupational exposure to disinfectants/cleaning products by developing new methods; and to study the association between occupational exposure to disinfectants/cleaning products and asthma control taking into account a possible HWE.First, job-exposure (JEM) and job-task-exposure matrices (JTEM) have been created using data from a random sample of women without asthma from a large prospective cohort of US nurses (NHSII: Nurse’s Health Study II). Second a new assessment method using a smartphone application with a barcode scanner and a database was designed to evaluate occupational exposure to disinfectants and cleaning products. The study of the association between occupational exposure to disinfectants and cleaning products and asthma control has used data from the French Epidemiological study on the genetics and environment of asthma. Longitudinal data were available on occupational history and asthma phenotypes. To control for a possible HWE, a marginal structural model (MSM) was used.For the first part, JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration. The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Through the smartphone application, 126 products were registered for 14 hospital workers of the pilot study. Information on components was available for all products in the database. The method developed is feasible and applicable to larger epidemiological studies. In the etiological part, a HWE was observed in the study sample. Even after controlling for a HWE, results did not allow concluding on the association between occupational exposures and control of asthma.Actuellement, l’asthme est la 1ère maladie professionnelle respiratoire. L’utilisation de produits de nettoyage et de désinfection est un facteur de risque émergent de l’asthme lié au travail, surtout dans le secteur de la santé. Cependant, les produits spécifiques en cause dans l’asthme restent à identifier. L’évaluation de l’exposition professionnelle aux produits de nettoyage et de désinfection est difficile dans les études épidémiologiques. De plus, le biais du travailleur sain (HWE) est important à considérer dans les études épidémiologiques sur l’asthme lié au travail.L’objectif de la thèse comportait deux aspects : 1) un aspect méthodologique visant à améliorer l’évaluation des expositions professionnelles aux produits de nettoyage et de désinfection en développant des méthodes novatrices ; 2) un aspect étiologique visant à estimer le rôle des expositions professionnelles dans le contrôle de l’asthme en prenant en compte un potentiel HWE.Tout d’abord, des matrices emplois-expositions (MEE) et emplois-tâches¬-expositions (METE) ont été développées via les données de femmes non-asthmatiques tirées au sort dans une cohorte prospective d’infirmières américaine (NHSII : Nurse’s Health Study II). Puis, une méthode d’évaluation des expositions professionnelles aux produits de nettoyage et de désinfection utilisant une application smartphone scannant les codes-barres de produits et une base de données (BDD) a été développée. L’étude du rôle des expositions professionnelles aux produits de nettoyage et de désinfection dans le contrôle de l’asthme a été réalisée dans l’étude Épidémiologique des facteurs Génétiques et Environnementaux de l'Asthme disposant de données longitudinales détaillées sur l’histoire professionnelle et les phénotypes d’asthme. Afin de prendre en compte un potentiel HWE, un modèle marginal structural (MMS) a été appliqué.Une hétérogénéité de l’estimation des expositions par les MEE et METE était observée dans la plupart des métiers infirmiers, sauf pour les infirmières exerçant aux urgences et dans l’administration/la formation. Nous avons montré que la METE était plus adaptée que la MEE pour estimer les expositions, en particulier pour les métiers infirmiers ayant des tâches hétérogènes. Via l’application, 126 produits ont été recueillis auprès de 14 personnels hospitaliers de l’étude pilote, et des informations sur les composés étaient disponibles pour tous les produits via la BDD associée. Cette étude a montré que ce nouvel outil était simple à mettre en place, facile et rapide à utiliser pour les participants, et permettait d’évaluer de façon précise les expositions aux différentes substances. Ces résultats confirment la faisabilité et l’intérêt de cette méthode et suggèrent son déploiement dans les études épidémiologiques. Dans la partie étiologique, nous avons observé la présence d’un HWE dans notre échantillon d’étude. Malgré la prise en compte de ce HWE en utilisant un MMS, les résultats des associations ne permettaient pas de conclure sur le rôle des expositions professionnelles dans le contrôle de l’asthme

Occupational exposure to disinfectants and asthma control in US nurses

International audienceDisinfectant use has been associated with adverse respiratory effects among healthcare workers. However, the specific harmful agents have not been elucidated. We examined the association between occupational exposure to disinfectants and asthma control in the Nurses' Health Study II, a large cohort of female nurses.Nurses with asthma were invited in 2014 to complete two questionnaires on their current occupation and asthma (response rate 80%). Asthma control was defined by the Asthma Control Test (ACT). Exposure to major disinfectants was evaluated by a job-task-exposure matrix (JTEM).Analyses included 4102 nurses with asthma (mean age 58 years). Asthma control was poor (ACT score 16-19) in 12% of nurses and very poor (ACT score ≤15) in 6% of nurses. Use of disinfectants to clean medical instruments (19% exposed) was associated with poorly (OR 1.37; 95% CI 1.05-1.79) and very poorly (OR 1.88, 95% CI 1.38-2.56) controlled asthma (ptrend=0.004, after adjustment for potential confounders). Using JTEM estimates, exposure to formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide and enzymatic cleaners was associated with poor asthma control (all ptrend<0.05); exposure to quaternary ammonium compounds and alcohol was not.Use of several disinfectants was associated with poor asthma control. Our findings suggest targets for future efforts to prevent worsening of asthma control in healthcare workers

Association of hand and arm disinfection with asthma control in US nurses

International audienceOBJECTIVES:To investigate the association between occupational exposure to disinfectants/antiseptics used for hand hygiene and asthma control in nurses.METHODS:In 2014, we invited female nurses with asthma drawn from the Nurses' Health Study II to complete two supplemental questionnaires on their occupation and asthma (cross-sectional study, response rate: 80%). Among 4055 nurses (mean age: 59 years) with physician-diagnosed asthma and asthma medication use in the past year, we examined asthma control, as defined by the Asthma Control Test (ACT). Nurses were asked about the daily frequency of hand hygiene tasks: 'wash/scrub hands with disinfectants/hand sanitizers' (hand hygiene) and 'wash/scrub arms with disinfecting products' (surrogate of surgical hand/arm antisepsis). Analyses were adjusted for age, race, ethnicity, smoking status and body mass index.RESULTS:Nurses with partly controlled asthma (ACT: 20-24, 50%) and poorly controlled asthma (ACT ≤19, 18%) were compared with nurses with controlled asthma (ACT=25, 32%). In separate models, both hand and arm hygiene were associated with poorly controlled asthma. After mutual adjustment, only arm hygiene was associated with poorly controlled asthma: OR (95% CI) for 10 times/day) and poor asthma control. Associations persisted after further adjustment for surfaces/instruments disinfection tasks.CONCLUSIONS:Frequency of hand/arm hygiene tasks in nurses was associated with poor asthma control. The results suggest an adverse effect of products used for surgical hand/arm antisepsis. This potential new occupational risk factor for asthma warrants further study

Occupational exposure to disinfectants and asthma incidence in U.S. nurses: A prospective cohort study

International audienceBackground: Exposure to disinfectants among healthcare workers has been associated with respiratory health effects, in particular, asthma. However, most studies are cross-sectional and the role of disinfectant exposures in asthma development requires longitudinal studies. We investigated the association between occupational exposure to disinfectants and incident asthma in a large cohort of U.S. female nurses. Methods: The Nurses’ Health Study II is a prospective cohort of 116 429 female nurses enrolled in 1989. Analyses included 61 539 participants who were still in a nursing job and with no history of asthma in 2009 (baseline; mean age: 55 years). During 277 744 person-years of follow-up (2009-2015), 370 nurses reported incident physician-diagnosed asthma. Occupational exposure was evaluated by questionnaire and a Job-Task-Exposure Matrix (JTEM). We examined the association between disinfectant exposure and subsequent asthma development, adjusted for age, race, ethnicity, smoking status, and body mass index. Results: Weekly use of disinfectants to clean surfaces only (23% exposed) or to clean medical instruments (19% exposed) was not associated with incident asthma (adjusted hazard ratio [95% confidence interval] for surfaces, 1.12 [0.87-1.43]; for instruments, 1.13 [0.87-1.48]). No association was observed between high-level exposure to specific disinfectants/cleaning products evaluated by the JTEM (formaldehyde, glutaraldehyde, bleach, hydrogen peroxide, alcohol quats, or enzymatic cleaners) and asthma incidence. Conclusions: In a population of late career nurses, we observed no significant association between exposure to disinfectants and asthma incidence. A potential role of disinfectant exposures in asthma development warrants further study among healthcare workers at earlier career stage to limit the healthy worker effect

Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England

Background: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. Methods: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts’ vaccination status as the main exposure while adjusting for confounders. Results: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35–0.72) and 0.69 (0.53–0.90) for receipt of two doses 8–90 and >90 days ago, respectively, and 0.34 (0.23–0.50) for vaccination with three doses 8–151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts’ infection risk: 0.45 (0.23–0.89). Conclusions: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose

Comparison of a Barcode-Based Smartphone Application to a Questionnaire to Assess the Use of Cleaning Products at Home and Their Association with Asthma Symptoms

International audienceHousehold disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00-1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors