Midwives' attitudes toward participation of pregnant individuals in a preventive vaccine hypothetical clinical trial.

INTRODUCTION: Pregnant individuals are frequently excluded from clinical trials. Yet, inclusion of Pregnant individuals is of interest in vaccinology including during health crisis. Promotion of clinical trials by midwives may facilitate the decision making of Pregnant individuals. Attitudes of midwives about pregnant individuals participation in a vaccine clinical trial have been little explored. METHODS: We conducted an anonymous survey from the 11th of September to the 11th of November 2020. Primary endpoint was the willingness to encourage Pregnant individuals to participate in a hypothetical respiratory syncytial virus (RSV) vaccine clinical trial. RESULTS: Among 398 midwives who answered the questionnaire, 113 (28.3 %) were likely to encourage Pregnant individuals to participate in the vaccine clinical trial, this proportion ranged from 25 % in senior midwives to 34.5 % among the students. After adjustment on age, parenthood, previous personal attitudes of vaccine hesitancy, and psychological antecedents of vaccinations (5C-model), the only predictor of the promotion of the clinical trial was the experience of vaccine education (evaluated by a 20-point score) with an adjusted odds ratio of 1.09 (1.01-1.18, p = 0.027) for a one-point increase. Vaccine hesitancy and psychological antecedents of vaccinations were not associated with a lower promotion of pregnant individuals trial participation by midwives. CONCLUSION: Few respondents were likely to encourage Pregnant individuals to participate in a vaccine clinical trial. Midwives who considered themselves to have a good training about vaccines were more prone to encourage Pregnant individuals to participate in a RSV vaccine clinical trial.

COVID-19 in health-care workers: lessons from SARS and MERS epidemics and perspectives for chemoprophylaxis and vaccines.

Introduction: The world is now facing the COVID-19 pandemic. Experience with SARS-CoV and MERS-CoV, and early reports about SARS-CoV-2 infection suggest that health-care settings and health-care workers (HCWs) are vulnerable in the context of the emergence of a new coronavirus. Areas covered: To highlight the need for prophylactic strategies particularly for HCWs, we identified SARS-CoV, MERS-CoV, and SARS-CoV-2 outbreaks in health-care settings and the incidence of infections in HCWs by a search on MEDLINE and MEDxRIV (for SARS-Cov-2). To identify prophylactic strategies against, we conducted a search on MEDLINE and clinicaltrials.gov about studies involving SARS-CoV, MERS-CoV, and SARS-CoV-2. Expert opinion: HCWs account for a great part of SARS, MERS, and SARS-CoV-2 infections, they may also contribute to the spread of the disease, particularly in health-care settings, and contribute to nosocomial outbreaks. Some preventive strategies were evaluated in previous emerging coronavirus epidemics, particularly in MERS-CoV. For COVID-19 prevention, different chemoprophylaxis with drug repositioning and new agents are under evaluation, and different vaccine candidates entered clinical development, with clinical trials. HCWs are a crucial target population for pre-exposure and post-exposure prophylaxis.

Intention to participate in a COVID-19 vaccine clinical trial and to get vaccinated against COVID-19 in France during the pandemic.

INTRODUCTION: The world is facing the COVID-19 pandemic. The development of a vaccine is challenging. We aimed to determine the proportion of people who intend to get vaccinated against COVID-19 in France or to participate in a vaccine clinical trial. METHODS: We conducted an anonymous on-line survey from the 26th of March to the 20th of April 2020. Primary endpoints were the intention to get vaccinated against COVID-19 if a vaccine was available or participate in a vaccine clinical trial. RESULTS: Three thousand two hundred and fifty nine individuals answered the survey; women accounted for 67.4% of the respondents. According to their statements, 2.512 participants (77.6%, 95% CI 76.2-79%) will certainly or probably agree to get vaccinated against COVID-19. Older age, male gender, fear about COVID-19, being a healthcare worker and individual perceived risk were associated with COVID-19 vaccine acceptance. Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. One thousand and five hundred and fifty respondents (47.6% 95% CI 45.9-49.3%) will certainly or probably agree to participate in a COVID-19 vaccine clinical trial. Older age, male gender, being a healthcare worker and individual perceived risk were associated with potential acceptance to participate in a COVID-19 vaccine clinical trial. Vaccine hesitancy was associated with refusal for participation in a COVID-19 vaccine clinical trial. CONCLUSIONS: Nearly 75% and 48% of the survey respondents were respectively likely to accept vaccination or participation in a clinical trial against COVID-19. Vaccine hesitancy will be the major barrier to COVID-19 vaccine uptake.

Primary physicians' attitudes toward their patients receiving a proposal to participate in a vaccine trial.

A trustworthy relationship between primary physicians (PPs) and their patients is crucial for vaccine acceptance. Little is known about attitudes of PPs toward participation of their patients in a preventive vaccine trial (PVT) proposed by investigation sites.A cross-sectional study was conducted in Auvergne-Rhône-Alpes region (France) including an anonymous questionnaire for general practitioners (GPs) and other specialists as well as face-to-face interviews. A scenario of a patient, with chronic medical conditions, invited to participate in a PVT and reporting this situation to his/her PP was drawn up. PPs' attitudes were assessed in quantitative approach by a 5-point Likert scale and in qualitative approach by semi-directed individual interviews.Among the 521 respondents to the questionnaire, 429 (82.3%) were GPs and 92 (17.7%) were other specialists. Only 7.5% (39/521) of respondents regularly practice clinical research. Confronted with the scenario, 312 respondents (59.8%) declared they would give their opinion spontaneously. Before giving their opinion, PPs would like more information about the trial (91.4%, n = 476). Whatever their attitude, 488 (93.7%) would be influenced by available safety data. Face-to-face interviews confirmed that PPs lack of knowledge about clinical research, and would like to obtain information from investigators, particularly about safety.PPs seem to be concerned by the decision of their patients to participate or not in a PVT but would like more information about the trial and clinical research before giving their opinion. Getting PPs to be more involved in the enrollment of patients in PVT may improve recruitment.

Anti-inflammatory properties of desipramine and fluoxetine.

BACKGROUND: Antidepressants are heavily prescribed drugs and have been shown to affect inflammatory signals. We examined whether these have anti-inflammatory properties in animal models of septic shock and allergic asthma. We also analysed whether antidepressants act directly on peripheral cell types that participate in the inflammatory response in these diseases. METHODS: The antidepressants desipramine and fluoxetine were compared in vivo to the glucocorticoid prednisolone, an anti-inflammatory drug of reference. In a murine model of lipopolysaccharides (LPS)-induced septic shock, animals received the drugs either before or after injection of LPS. Circulating levels of tumour necrosis factor (TNF)-alpha and mortality rate were measured. In ovalbumin-sensitized rats, the effect of drug treatment on lung inflammation was assessed by counting leukocytes in bronchoalveolar lavages. Bronchial hyperreactivity was measured using barometric plethysmography. In vitro production of TNF-alpha and Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES) from activated monocytes and lung epithelial cells, respectively, was analysed by immunoassays. Reporter gene assays were used to measure the effect of antidepressants on the activity of nuclear factor-kappaB and activator protein-1 which are involved in the control of TNF-alpha and RANTES expression. RESULTS: In the septic shock model, all three drugs given preventively markedly decreased circulating levels of TNF-alpha and mortality (50% mortality in fluoxetine treated group, 30% in desipramine and prednisolone treated groups versus 90% in controls). In the curative trial, antidepressants had no statistically significant effect, while prednisolone still decreased mortality (60% mortality versus 95% in controls). In ovalbumin-sensitized rats, the three drugs decreased lung inflammation, albeit to different degrees. Prednisolone and fluoxetine reduced the number of macrophages, lymphocytes, neutrophils and eosinophils, while desipramine diminished only the number of macrophages and lymphocytes. However, antidepressants as opposed to prednisolone did not attenuate bronchial hyperreactivity. In vitro, desipramine and fluoxetine dose-dependently inhibited the release of TNF-alpha from LPS-treated monocytes. In lung epithelial cells, these compounds decreased TNF-alpha-induced RANTES expression as well as the activity of nuclear factor-kappaB and activator protein-1. CONCLUSION: Desipramine and fluoxetine reduce the inflammatory reaction in two animal models of human diseases. These antidepressants act directly on relevant peripheral cell types to decrease expression of inflammatory mediators probably by affecting their gene transcription. Clinical implications of these observations are discussed.