Brand-specific estimates of influenza vaccine effectiveness for the 2021-2022 season in Europe: results from the DRIVE multi-stakeholder study platform.

Introduction: Development of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017-2018 to its final season in 2021-2022. Methods: In 2021-2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis. Results: In 2021-2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%-93%) for any vaccine and 81% (22%-95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%-83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%-97%) for any vaccine in adults 18-64 years (TND hospital setting), and 38% (1%-62%) in children 6 months-6 years (population-based cohort, mixed setting). Discussion: Over five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

Effectiveness and Medicoeconomic Evaluation of Home Monitoring of Patients With Mild COVID-19: Covidom Cohort Study.

BACKGROUND: Covidom was a telemonitoring solution for home monitoring of patients with mild to moderate COVID-19, deployed in March 2020 in the Greater Paris area in France to alleviate the burden on the health care system. The Covidom solution included a free mobile application with daily monitoring questionnaires and a regional control center to quickly handle patient alerts, including dispatching emergency medical services when necessary. OBJECTIVE: This study aimed to provide an overall evaluation of the Covidom solution 18 months after its inception in terms of effectiveness, safety, and cost. METHODS: Our primary outcome was to measure effectiveness using the number of handled alerts, response escalation, and patient-reported medical contacts outside of Covidom. Then, we analyzed the safety of Covidom by assessing its ability to detect clinical worsening, defined as hospitalization or death, and the number of patients with clinical worsening without any preceding alert. We evaluated the cost of Covidom and compared the cost of hospitalization for Covidom and non-Covidom patients with mild COVID-19 cases seen in the emergency departments of the largest network of hospitals in the Greater Paris area (Assistance Publique-Hôpitaux de Paris). Finally, we reported on user satisfaction. RESULTS: Of the 60,073 patients monitored by Covidom, the regional control center handled 285,496 alerts and dispatched emergency medical services 518 times. Of the 13,204 respondents who responded to either of the follow-up questionnaires, 65.8% (n=8690) reported having sought medical care outside the Covidom solution during their monitoring period. Of the 947 patients who experienced clinical worsening while adhering to daily monitoring, only 35 (3.7%) did not previously trigger alerts (35 were hospitalized, including 1 who died). The average cost of Covidom was €54 (US $1=€0.8614) per patient, and the cost of hospitalization for COVID-19 worsening was significantly lower in Covidom than in non-Covidom patients with mild COVID-19 cases seen in the emergency departments of Assistance Publique-Hôpitaux de Paris. The patients who responded to the satisfaction questionnaire had a median rating of 9 (out of 10) for the likelihood of recommending Covidom. CONCLUSIONS: Covidom may have contributed to alleviating the pressure on the health care system in the initial months of the pandemic, although its impact was lower than anticipated, with a substantial number of patients having consulted outside of Covidom. Covidom seems to be safe for home monitoring of patients with mild to moderate COVID-19.

Investigating confounding in network-based test-negative design influenza vaccine effectiveness studies-Experience from the DRIVE project.

BACKGROUND: Establishing a large study network to conduct influenza vaccine effectiveness (IVE) studies while collecting appropriate variables to account for potential bias is important; the most relevant variables should be prioritized. We explored the impact of potential confounders on IVE in the DRIVE multi-country network of sites conducting test-negative design (TND) studies. METHODS: We constructed a directed acyclic graph (DAG) to map the relationship between influenza vaccination, medically attended influenza infection, confounders, and other variables. Additionally, we used the Development of Robust and Innovative Vaccines Effectiveness (DRIVE) data from the 2018/2019 and 2019/2020 seasons to explore the effect of covariate adjustment on IVE estimates. The reference model was adjusted for age, sex, calendar time, and season. The covariates studied were presence of at least one, two, or three chronic diseases; presence of six specific chronic diseases; and prior healthcare use. Analyses were conducted by site and subsequently pooled. RESULTS: The following variables were included in the DAG: age, sex, time within influenza season and year, health status and comorbidities, study site, health-care-seeking behavior, contact patterns and social precautionary behavior, socioeconomic status, and pre-existing immunity. Across all age groups and settings, only adjustment for lung disease in older adults in the primary care setting resulted in a relative change of the IVE point estimate >10%. CONCLUSION: Our study supports a parsimonious approach to confounder adjustment in TND studies, limited to adjusting for age, sex, and calendar time. Practical implications are that necessitating fewer variables lowers the threshold for enrollment of sites in IVE studies and simplifies the pooling of data from different IVE studies or study networks.

A cross-sectional study on infectious health risks regarding freshwater sports practice in Brittany, France.

Freshwater sports expose practitioners to pathogens in the water environment and may result in infection. In French Brittany, these infections are particularly worrying, especially since 2016 with an increase in the incidence of leptospirosis reaching 1 case per 100,000 inhabitants, which represents the highest incidence observed since 1920. We aimed to estimate the prevalence of infectious diseases related to freshwater sports practice and to identify the factors associated with these infections among freshwater sports licensees in Brittany, France. From March 18, 2019, to May 8, 2019, we interviewed freshwater sports licensees (online study) and club presidents and instructors (phone study) in Brittany. Licensee participants were 18 years old or more and practiced at least one freshwater sport in one of the 79 Brittany clubs. We used logistic regression models to study the association between our variables of interest and potential risk factors. In total, 551 licensees (20.3% of the total number of licensees) and 38 clubs (48.1%) were surveyed. Among the licensees, 29 (5.3%) reported being diagnosed with leptospirosis, of which 12 (41.3%) occurred in the last 5 years. The most reported symptoms were skin irritation/itchy skin (24.3%) and 39 individuals (7.1%) reported at least one hospitalization in their lifetime for a disease related to freshwater sports. The occurrence of leptospirosis was negatively associated with boarding from a pontoon (odds ratio (OR)=0.20, 95% confidence interval (95% CI) 0.06-0.56), practicing for less than 4 years (OR=0.17, 95% CI 0.04-0.56) compared to more than 10 years, and the occurrence of leptospirosis was positively associated with taking a soapy shower after practice (OR=4.38, 95% CI 1.90-10.51). Eskimo roll was positively associated with the occurrence of otitis and conjunctivitis (OR=3.22, 95% CI 1.82-6.03), and skin irritation/itchy skin (OR=1.66, 95% CI 0.99-2.84). Otitis, conjunctivitis, and skin irritation/itchy skin are the most commonly reported freshwater sport-related diseases in French Brittany. Despite a good level of knowledge of prevention measures, their implementation by licensees and clubs remains low. Further studies are needed to identify practices associated with infectious risk in freshwater sports.

Association between mental disorders and COVID-19 outcomes among inpatients in France: A retrospective nationwide population-based study.

BACKGROUND: Mental disorders are at-risk of severe COVID-19 outcomes. There is limited and heterogeneous national data in hospital settings evaluating the risks associated with any pre-existing mental disorder, and susceptible subgroups. Our study aimed to investigate the association between pre-existing psychiatric disorders and outcomes of adults hospitalised for COVID-19. METHOD: We used data obtained from the French national hospital database linked to the state-level psychiatric registry. The primary outcome was 30-days in-hospital mortality. Secondary outcomes were to compare the length of hospital stay, Intensive Care Unit (ICU) admission and ICU length. Propensity score matching analysis was used to control for COVID-19 confounding factors between patients with or without mental disorder and stratified by psychiatric subgroups. RESULTS: Among 97 302 adults hospitalised for COVID-19 from March to September 2020, 10 083 (10.3%) had a pre-existing mental disorder, mainly dementia (3581 [35.5%]), mood disorders (1298 [12.9%]), anxiety disorders (995 [9.9%]), psychoactive substance use disorders (960 [9.5%]), and psychotic disorders (866 [8.6%]). In propensity-matched analysis, 30-days in-hospital mortality was increased among those with at least one pre-existing mental disorder (hazard ratio (HR) 1.15, 95% CI 1.08-1.23), psychotic disorder (1.90, 1.24-2.90), and psychoactive substance disorders (1.53, 1.10-2.14). The odds of ICU admission were consistently decreased for patients with any pre-existing mental disorder (OR 0.83, 95% CI 0.76-0.92) and for those with dementia (0.64, 0.53-0.76). CONCLUSION: Pre-existing mental disorders were independently associated with in-hospital mortality. These findings underscore the important need for adequate care and targeted interventions for at-risk individuals with severe mental illness.

In-hospital and midterm post-discharge complications of adults hospitalised with respiratory syncytial virus infection in France, 2017-2019: an observational study.

OBJECTIVES: The purpose of this study was to describe the clinical characteristics and in-hospital and post-discharge outcomes of respiratory syncytial virus (RSV) infection among adults hospitalised with influenza-like illness (ILI) and compared against patients admitted for influenza. METHODS: Adults hospitalised with ILI were prospectively included from five French university hospitals over two consecutive winter seasons (2017/2018 and 2018/2019). RSV and influenza virus were detected by multiplex reverse transcription PCR on nasopharyngeal swabs. RSV-positive patients were compared to RSV-negative and influenza-positive hospitalised patients. Poisson regression models were used to estimate the adjusted prevalence ratio (aPR) associated with in-hospital and post-discharge outcomes between RSV and influenza infections. The in-hospital outcome was a composite of the occurrence of at least one complication, length of stay ≥7 days, intensive care unit admission, use of mechanical ventilation and in-hospital death. Post-discharge outcome included 30- and 90-day all-cause mortality and 90-day readmission rates. RESULTS: Overall, 1428 hospitalised adults with ILI were included. RSV was detected in 8% (114 of 1428) and influenza virus in 31% (437 of 1428). Patients hospitalised with RSV were older than those with influenza (mean age 73.0 versus 68.8 years, p=0.015) with a higher frequency of chronic respiratory or cardiac disease (52% versus 39%, p=0.012, and 52% versus 41%, p=0.039, respectively) and longer hospitalisation duration (median stay 8 versus 6 days, p<0.001). Anti-influenza therapies were less prescribed among RSV patients than influenza patients (20% versus 66%, p<0.001). In-hospital composite outcome was poorer in RSV patients (aPR 1.5, 95% CI 1.1-2.1) than in those hospitalised with influenza. No difference was observed for the post-discharge composite outcome (aPR 1.1, 95% CI 0.8-1.6). CONCLUSION: RSV infection results in serious respiratory illness, with worse in-hospital outcomes than influenza and with similar midterm post-discharge outcomes.

Brand-specific influenza vaccine effectiveness estimates during 2019/20 season in Europe - Results from the DRIVE EU study platform.

DRIVE (Development of Robust and Innovative Vaccine Effectiveness) is an IMI funded public-private platform that aims to annually estimate brand-specific influenza vaccine effectiveness (IVE), for public health and regulatory purposes. IVE analyses and reporting are conducted by public partners in the consortium. In 2019/20, four primary care-based test-negative design (TND) studies (Austria, England, Italy (n = 2)), eight hospital-based TND studies (Finland, France, Italy, Romania, Spain (n = 4)), and one population-based cohort study (Finland) were conducted. The COVID-19 pandemic affected influenza surveillance in all participating study sites, therefore the study period was truncated on February 29, 2020. Age-stratified (6 m-17y, 18-64y, ≥65y), confounder-adjusted, site-specific adjusted IVE estimates were calculated and pooled through meta-analysis. Parsimonious confounder-adjustment was performed, adjusting the estimates for age, sex and calendar time. TND studies included 3531 cases (351 vaccinated) and 5546 controls (1415 vaccinated) of all ages. IVE estimates were available for 8/11 brands marketed in Europe in 2019. Most children and adults < 64y were captured in primary care setting and the most frequently observed vaccine brand was Vaxigrip Tetra. The estimate against any influenza for Vaxigrip Tetra in primary care setting was 61% (95%CI 38-77) in children and 32% (95%CI -13-59) in adults up to 64y. Most adults ≥ 65y were captured in hospital setting and the most frequently observed brand was Fluad, with an estimate of 52% (95%CI 27-68). The population-based cohort covered 511,854 person-years and two vaccine brands. In children aged 2-6y, the IVE against any influenza was 68% (95%CI 58-75) for Fluenz Tetra and 71% (56-80) for Vaxigrip Tetra. In adults ≥ 65y, IVE against any influenza was 29% (20-36) for Vaxigrip Tetra. DRIVE is a growing platform. Public health institutes with surveillance data and hospitals in countries with high influenza vaccine coverage are encouraged to join DRIVE.

Challenges and Adaptation of a European Influenza Vaccine Effectiveness Study Platform in Response to the COVID-19 Emergence: Experience from the DRIVE Project.

The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project is a public-private partnership aiming to build capacity in Europe for yearly estimation of brand-specific influenza vaccine effectiveness (IVE). DRIVE is a five-year project funded by IMI (Innovative Medicines Initiative). It was initiated as a response to the guidance on influenza vaccines by EMA (European Medicines Agency), which advised vaccine manufacturers to work with public health institutes to set up a joint IVE study platform. The COVID-19 pandemic reached Europe in February 2020 and overlapped with the 2019/2020 influenza season only in the last weeks. However, several elements of the DRIVE study network were impacted. The pandemic specifically affected the study sites' routines and the subsequent assessment of the 2019/20 influenza season. Moreover, the current social distancing measures and lockdown policies across Europe are expected to also limit the circulation of influenza for the 2020/21 season, and therefore the impact of COVID-19 will be higher than in the season 2019/20. Consequently, DRIVE has planned to adapt its study platform to the COVID-19 challenge, encompassing several COVID-19 particularities in the study procedures, data collection and IVE analysis for the 2020/21 season. DRIVE will study the feasibility of implementing these COVID-19 components and establish the foundations of future COVID-19 vaccine effectiveness studies.

Seasonal influenza vaccine uptake and vaccine refusal among pregnant women in France: results from a national survey.

Pregnant women and infants are at high risk for severe influenza and many countries, including France, recommend annual influenza immunization during pregnancy. We aimed to estimate influenza vaccination and refusal rates and assess associated factors among pregnant women during the 2015-16 season in France. We used data from a national representative sample of women who gave birth in March 2016 and were interviewed before hospital discharge (N = 11,752). In the multivariable analysis, robust Poisson regression models were used to study associations with maternal characteristics and prenatal care characteristics. Influenza vaccine coverage among pregnant women was 7.4% (95% confidence interval [CI]: 6.9-7.9). Only 24.9% (95% CI: 24.2-25.7) of women said that they received a care provider proposal for vaccination and 70.4% (95% CI: 68.7-72.0) of these declined it. Vaccine uptake was associated with low parity (prevalence ratio [PR] = 2.1; 95% CI: 1.4-3.2 for parity 0 vs ≥ 3), high educational level (PR = 2.5; 95% CI: 2.0-3.2), healthcare occupation during pregnancy (PR = 1.8; 95% CI: 1.5-2.1) and preexisting conditions at risk for influenza (PR = 1.7; 95% CI: 1.3-2.2). Women were more frequently vaccinated when their main care provider was a general practitioner. Multiparae women and those with medium or low educational level were significantly more likely than others to decline influenza vaccine after a provider proposal. Influenza vaccine coverage is very low in France, mainly because of infrequent care provider proposals and also frequent women's refusals. Effective interventions should be designed to promote vaccination among medical professionals and reduce vaccine hesitancy among pregnant women.

Barriers to publishing in biomedical journals perceived by a sample of French researchers: results of the DIAzePAM study.

BACKGROUND: As publishing is essential but competitive for researchers, difficulties in writing and submitting medical articles to biomedical journals are disabling. The DIAzePAM (Difficultés des Auteurs à la Publication d'Articles Médicaux) survey aimed to assess the difficulties experienced by researchers in the AP-HP (Assistance Publique - Hôpitaux de Paris, i.e., Paris Hospitals Board, France), the largest public health institution in Europe, when preparing articles for biomedical journals. The survey also aimed to assess researchers' satisfaction and perceived needs. METHODS: A 39-item electronic questionnaire based on qualitative interviews was addressed by e-mail to all researchers registered in the AP-HP SIGAPS (Système d'Interrogation, de Gestion et d'Analyse des Publications Scientifiques) bibliometric database. RESULTS: Between 28 May and 15 June 2015, 7766 researchers should have received and read the e-mail, and 1191 anonymously completed the questionnaire (<45 years of age: 63%; women: 55%; physician: 81%; with PhD or Habilitation à Diriger des recherches--accreditation to direct research--: 45%). 94% of respondents had published at least one article in the previous 2 years. 76% of respondents felt they were not publishing enough, mainly because of lack of time to write (79%) or submit (27%), limited skills in English (40%) or in writing (32%), and difficulty in starting writing (35%). 87% of respondents would accept technical support, especially in English reediting (79%), critical reediting (63%), formatting (52%), and/or writing (41%), to save time (92%) and increase high-impact-factor journal submission and acceptance (75%). 79% of respondents would appreciate funding support for their future publications, for English reediting (56%), medical writing (21%), or publication (38%) fees. They considered that this funding support could be covered by AP-HP (73%) and/or by the added financial value obtained by their department from previous publications (56%). CONCLUSIONS: The DIAzePAM survey highlights difficulties experienced by researchers preparing articles for biomedical journals, and details room for improvement.