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Objectives Vaccination of the at-risk population against influenza by pharmacists was widely implemented in France in 2019. Only little data are available about the population using this service. We have explored the characteristics and determinants of the at-risk population vaccinated in pharmacy through a web-based cohort during the 2019–20 winter season. Methods This study is based on the data of the profile survey of at-risk over-18 vaccinated participants of the cohort GrippeNet.fr, for the 2019–20 winter season. Population characteristics were described using the inclusion questionnaire data. Factors associated with pharmacy influenza vaccination were analysed through a logistic regression model. Key findings In total, 3144 people were included in the study. 50.2% (N = 1577) of them were women and 65.5% (N = 2060) were over 65 years old. 29.5% (N = 928) of participants were vaccinated in pharmacy. 73.1% (N = 678) of participants vaccinated in pharmacy were over 65 years old and 46.6% (N = 432) had a treatment for one or more chronic disease. Factors positively associated with being vaccinated by a pharmacist were: being a man (OR = 1.25, 95% confidence interval [1.06–1.47]), being over 65 years old (OR = 1.97 [1.49–2.63]), living in a test region (OR = 1.62 [1.29–2.02] and 1.72 [1.43–2.07] depending on the year of the implementation of the experimentation) and being vaccinated against influenza in 2018/2019 (OR = 1.71 [1.32–2.21]). Factors negatively associated were: taking a chronic treatment (OR = 0.83 [0.70–0.97]), and living alone (OR = 1.40 [1.17–1.67] and being in contact with sick people (OR = 0.68 [0.50–0.93]). Conclusions This study confirmed some factors associated with pharmacy influenza vaccination and feeds the debate on other uncertain factors. These findings can support public health authorities’ willingness to enhance pharmacists’ involvement in the future country-wide vaccination campaign. Our study also highlights the necessity to further investigate the impact of this measure in a few years.

Ethics approval and consent to participate.In Belgium and France, there were no specific ethics approval requiredfor the present study. However, the Belgian sentinel network wasapproved as a whole by the Ethical Committees of the Scientific Societyof Flemish GPs and the Catholic University of Louvain (UCL). In France,the sentinel protocol was approved by the French Data ProtectionAgency (CNIL#471393) and the French ethical research committee.In Spain, the protocol was approved by the Health Sentinel NetworkCommittee, according to the Order SAN/620/2016, that regulates theorganization and functioning of the Health Sentinel Network of Castileand León (BOCYL nº 132, 11 July 2016). Consent was obtained from allindividual participants included in the study. An email was sent to thephysicians of the sentinel networks, with information and a link to acceptor decline their participation.; International audience; BackgroundThe knowledge of risk perceptions in primary care could help health authorities to manage epidemics.MethodsA European multi-center cross-sectional study was conducted in France, Belgium and Spain to describe the perceptions, the level of anxiety and the feeling of preparedness of primary healthcare physicians towards the COVID-19 infection at the beginning of the pandemic. The factors associated with the feeling of preparedness were studied using multivariate logistic regressions.ResultsA total of 511 physicians participated to the study (response rate: 35.2%). Among them, only 16.3% (n=82) were highly anxious about the pandemic, 50.6% (n=254) had the feeling to have a high level of information, 80.5% (n=409) found the measures taken by the health authorities suitable to limit the spread of COVID-19, and 45.2% (n=229) felt prepared to face the epidemic. Factors associated with feeling prepared were: being a Spanish practitioner (adjusted OR=4.34; 95%CI [2.47; 7.80]), being a man (aOR=2.57, 95%CI [1.69; 3.96]), finding the measures taken by authorities appropriate (aOR=1.72, 95%CI [1.01; 3.00]) and being highly informed (aOR=4.82, 95%CI [2.62; 9.19]).ConclusionsRegarding the dramatic evolution of the pandemic in Europe in the weeks following the study, it appears that information available at this time and transmitted to the physicians could have given a wrong assessment of the spread and the severity of the disease. It seems essential to better integrate the primary care physicians into the information, training and protection channels. A comparison between countries could help to select the most effective measures in terms of information and communication.

Concomitant nonsteroidal anti-inflammatory drug (NSAIDs) and antithrombotic drug use is associated with an increased risk of bleeding, mainly gastrointestinal. The goal of this study was to quantify the transient increase in the risk of hospitalization for bleeding associated with NSAID use in patients treated with antiplatelet agents or anticoagulants. We performed an unidirectional case-crossover study using the EGB (Echantillon generaliste de beneficiaires), a permanent random sample of the French nationwide health database. Patients receiving antithrombotic therapy and hospitalized for bleeding between 2009 and 2017 were included. We compared their NSAID exposure during a 15-day hazard window immediately prior to hospital admission to three earlier 15-day control windows. The risk of hospitalization for bleeding associated with the recent use of NSAIDs was estimated using conditional logistic regression to estimate odds ratios. During the study period, 33 patients treated with anticoagulants and 253 treated with antiplatelet agents received NSAIDs and were included in the case-crossover analysis. We found an increased risk of hospitalization for gastrointestinal bleeding after exposure to NSAIDs with an adjusted OR of 3.59 (95%CI, 1.58;8.17) in patients receiving anticoagulant therapy and 1.44 (95%CI, 1.07;1.94) in patients receiving antiplatelet therapy. The risk of non-gastrointestinal bleeding was also increased after exposure to NSAIDs with an adjusted OR of 2.72 (95%CI, 1.23;6.04) in patients exposed to anticoagulant therapy. The risk of gastrointestinal and non-gastrointestinal bleeding increases after NSAID use in patients treated with anticoagulants, while the risk of gastrointestinal bleeding increases, but to a lesser extent in those treated with antiplatelets. This article is protected by copyright. All rights reserved.

International audience; Background: The protocol study will focus on the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection as well as the history, symptoms, and risk factors for SARS-CoV-2 in four primary health-care workers (PHCWs) and their household contacts in metropolitan France. Methods: Here, we propose a protocol for a nationwide survey to determine the seroprevalence of IgG antibodies to SARS-CoV-2 achieved by vaccination and/or natural protection in four PHCW populations (general practitioners, pediatricians, pharmacists and assistants, and dentists and assistants) and their household contacts. Participants will be included from June to July 2021 (Phase 1) among PHCW populations located throughout metropolitan France. They will be asked to provide a range of demographic and behavioral information since the first SARS-CoV-2 wave and a self-sampled dried blood spot. Phase 1 will involve also a questionnaire and serological study of PHCWs’ household contacts. Seroprevalence will be estimated using two ELISAs designed to detect specific IgG antibodies to SARS-CoV-2 in humoral fluid, and these results will be confirmed using a virus neutralization test. This study will be repeated from November to December 2021 (Phase 2) to evaluate the evolution of immune status achieved by vaccination and/or natural protection of PHCWs and to describe the history of exposure to SARS-CoV-2.

Bisphosphonates are widely used in the treatment of women at risk of osteoporotic hip fracture, however, the overall effectiveness of bisphosphonates in the prevention of osteoporotic fractures has not been studied in real life. To investigate whether the use of bisphosphonates in women aged 50 years and over is associated with a decrease in hospitalization for osteoporotic hip fractures, a historical prospective cohort study was conducted between 2009 and 2016 from a permanent representative sample consisting of 1/97 of the French health insurance beneficiaries. Bisphosphonate use was defined according to medication persistence and adherence regarding bisphosphonate dispensations. The primary outcome was the hospitalization rate for osteoporotic hip fracture. Among the 81,268 women included, 2005 were exposed to bisphosphonates. The median time of bisphosphonate exposure was 12 (IQR, 3–29) and 17 (IQR, 5–42) months for the persistence and adherence definitions, respectively. Exposure to bisphosphonates was not associated with a decrease in hospitalization for hip fracture: weighted HRadherence = 0.66 (95% CI, 0.33 to 1.33), HRpersistance = 0.77 (95% CI, 0.38 to 1.57). In real life, bisphosphonate use does not appear to reduce hospitalization for hip fractures, as to date, it is probably prescribed as primary prevention and for a duration too short to be effective.

International audience; Background: To limit the spread of SARS-CoV-2 several countries implemented measures to reduce the number of contacts such as a national lockdown. We estimated the impact of the first lockdown on the burden of COVID-19 in the community in France.Methods: Physicians participating in the French Sentinelles network reported the number of patients with an acute respiratory infection (ARI) seen in consultation and performed nasopharyngeal swabs in a sample of these patients (first patient of the week). The swabs were tested by RT-PCR for the presence of SARS-CoV-2. Clinical and virological data were combined to estimate ARI incidence attributable to SARS-CoV-2 from 17 March to 10 May 2020.Results: The incidence of ARI attributable to COVID-19 decreased after the second week of the lockdown period from 142 (95%CI [101; 183]) to 41 (95%CI [21; 60]) per 100,000 population. A decrease was observed in all areas in metropolitan France. The youngest age groups (

International audience; Influenza viruses cause seasonal epidemics whose intensity varies according to the circulating virus type and subtype. We aim to estimate influenza-like illness (ILI) incidence attributable to influenza viruses in France from October 2014 to May 2019. Physicians participating in the French Sentinelles network reported the number of patients with ILI seen in consultation and performed nasopharyngeal swabs in a sample of these patients. The swabs were tested by RT-PCR for the presence of influenza viruses. These clinical and virological data were combined to estimate ILI incidence attributable to influenza viruses by subtypes and age groups. Influenza incidence rates over seasons ranged from 1.9 (95% CI, 1.9; 2.0) to 3.4% (95% CI, 3.2; 3.6) of the population. Each season, more than half of ILI cases were attributable to influenza. Children under 15 years were the most affected, with influenza incidence rates ranging from 3.0 (95% CI, 2.8;3.3) to 5.7% (95% CI, 5.3;6.1). Co-circulation of several (sub)types of influenza viruses was observed each year, except in 2016/2017 where A(H3N2) viruses accounted for 98.0% of the influenza cases. Weekly ILI incidences attributable to each influenza virus (sub)type were mostly synchronized with ILI incidence, except in 2014/2015 and 2017/2018, where incidence attributable to type B viruses peaked few weeks later. The burden of medically attended influenza among patients with ILI is significant in France, varying considerably across years and age groups. These results show the importance of influenza surveillance in primary care combining clinical and virological data.

As countries in Europe gradually relaxed lockdown restrictions after the first wave, test–trace–isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels1,2. Reviewing their shortcomings can provide elements to consider in light of the second wave that is currently underway in Europe. Here we estimate the rate of detection of symptomatic cases of COVID-19 in France after lockdown through the use of virological3 and participatory syndromic4 surveillance data coupled with mathematical transmission models calibrated to regional hospitalizations2. Our findings indicate that around 90,000 symptomatic infections, corresponding to 9 out 10 cases, were not ascertained by the surveillance system in the first 7 weeks after lockdown from 11 May to 28 June 2020, although the test positivity rate did not exceed the 5% recommendation of the World Health Organization (WHO)5. The median detection rate increased from 7% (95% confidence interval, 6–8%) to 38% (35–44%) over time, with large regional variations, owing to a strengthening of the system as well as a decrease in epidemic activity. According to participatory surveillance data, only 31% of individuals with COVID-19-like symptoms consulted a doctor in the study period. This suggests that large numbers of symptomatic cases of COVID-19 did not seek medical advice despite recommendations, as confirmed by serological studies6,7. Encouraging awareness and same-day healthcare-seeking behaviour of suspected cases of COVID-19 is critical to improve detection. However, the capacity of the system remained insufficient even at the low epidemic activity achieved after lockdown, and was predicted to deteriorate rapidly with increasing incidence of COVID-19 cases. Substantially more aggressive, targeted and efficient testing with easier access is required to act as a tool to control the COVID-19 pandemic. The testing strategy will be critical to enable partial lifting of the current restrictive measures in Europe and to avoid a third wave. Analyses of virological and surveillance data in France show that a substantial proportion of symptomatic cases of COVID-19 have remained undetected and that easily accessible and efficient testing is required to control the pandemic.

International audience; In France, social distancing measures have been adopted to contain the spread of COVID-19, culminating in national Lockdowns. The use of hand washing, hydro-alcoholic rubs and mask-wearing also increased over time. As these measures are likely to impact the transmission of many communicable diseases, we studied the changes in common infectious diseases incidence in France during the first year of COVID-19 circulation. We examined the weekly incidence of acute gastroenteritis, chickenpox, acute respiratory infections and bronchiolitis reported in general practitioner networks since January 2016. We obtained search engine query volume for French terms related to these diseases and sales data for relevant drugs over the same period. A periodic regression model was fit to disease incidence, drug sales and search query volume before the COVID-19 period and extrapolated afterwards. We compared the expected values with observations made in 2020. During the first lockdown period, incidence dropped by 67% for gastroenteritis, by 79% for bronchiolitis, by 49% for acute respiratory infection and 90% for chickenpox compared to the past years. Reductions with respect to the expected incidence reflected the strength of implemented measures. Incidence in children was impacted the most. Reduction in primary care consultations dropped during a short period at the beginning of the first lockdown period but remained more than 95% of the expected value afterwards. In primary care, the large decrease in reported gastroenteritis, chickenpox or bronchiolitis observed during the period where many barrier measures were implemented imply that the circulation of common viruses was reduced and informs on the overall effect of these measures.

A novel testing policy was implemented in May in France to systematically screen potential COVID-19 infections and suppress local outbreaks while lifting lockdown restrictions. 20,777 virologically-confirmed cases were notified in mainland France from May 13, 2020 (week 20, end of lockdown) to June 28 (week 26). Accounting for missing data, positive tests before symptom onset, and the delay from symptom onset to test, this corresponds to 14,061 [95% CI 13,972-14,156] cases with symptom onset during this period, a likely underestimation of the real number. Using age-stratified transmission models parameterized to behavioral data and calibrated to regional hospital admissions, we estimated that 103,907 [95% CI 90,216-116,377] COVID-19 symptomatic cases occurred, suggesting that 9 out of 10 cases with symptoms were not ascertained. Median detection rate increased from 7% [6-8]% to 38% [35-44]% over time, with large regional variations. Healthcare-seeking behavior in COVID-19 suspect cases remained low (31%). Model projections for the incidence of symptomatic cases (6.7 [5.8, 7.4] per 100,000 in week 26) were compatible with estimates from participatory surveillance, provided that 80% of suspect cases consulted. Encouraging awareness and same-day healthcare-seeking behavior in suspect cases is critical to improve detection. The capacity of the system remained however insufficient even at the low levels of viral circulation achieved after lockdown, and was predicted to deteriorate rapidly for increasing epidemic activity. Substantially more aggressive, targeted, and efficient testing with easier access is required to act as a pandemic-fighting tool. These elements should be considered in light of the currently observed increase of cases in France and other European countries.

As countries in Europe gradually relaxed lockdown restrictions after the first wave, test-trace-isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels

International audience; Purpose: Drug-drug interactions (DDIs) require monitoring in an aging population with increasing polypharmacy exposure. We aimed to estimate the prevalence of exposure to potential DDIs using the French healthcare insurance system database, for six DDIs with various clinical relevance: angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs (ARBs-ACEIs + NSAIDs), antiplatelet agents and NSAIDs (AAP + NSAIDs), serotonergic drugs and tramadol (SD + T), statins and macrolides (S + M), oral anticoagulant and NSAIDs (OAC + NSAIDs), and colchicine and macrolides (C + M).Methods: We used exhaustive healthcare data from a 1/97th random sample of the population covered by the French health insurance system (EGB) between 2006 and 2016. Exposure to a DDI was defined as overlapping exposure to two interacting drugs. The prevalence of exposure was estimated by year.Results: Prevalence of exposure in 2016 was estimated at 3.7% for ARBs-ACEIs + NSAIDs, 1.5% for AAP + NSAIDs, 0.76% for SD + T, 0.36% for S + M, 0.24% for AOC + NSAIDs, and 0.02% for C + M. In 26% to 58% of episodes of exposure, the two interacting drugs were prescribed by the same physician and dispensed by the same pharmacy the same day. Between 2006 and 2016, the yearly prevalence was increasing for SD + T and for DDIs involving NSAIDs, and it was decreasing for those involving macrolides.Conclusion: Exposures to potential DDIs in France are not uncommon with a high proportion resulting from a co-prescription by the same physician. Monitoring the prevalence of exposure to DDIs is needed to implement prevention measures. Administrative data enable this surveillance in large and representative cohorts.

Several French regions where coronavirus disease (COVID-19) has been reported currently show a renewed increase in ILI cases in the general practice-based Sentinelles network. We computed the number of excess cases by region from 24 February to 8 March 2020 and found a correlation with the number of reported COVID-19 cases so far. The data suggest larger circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the French population than apparent from confirmed cases.

The recent emergence of the SARS-CoV-2 in China has raised the spectre of a novel, potentially catastrophic pandemic in both scientific and lay communities throughout the world. In this particular context, people have been accused of being excessively pessimistic regarding the future consequences of this emerging health threat. However, consistent with previous research in social psychology, a large survey conducted in Europe in the early stage of the COVID-19 epidemic shows that the majority of respondents was actually overly optimistic about the risk of infection. https://psyarxiv.com/364qj/

Background The safety of non-steroids anti-inflammatory drugs (NSAIDs) in the context of pharyngitis is doubtful with contradictory results in the literature. Objective To evaluate the risk of peritonsillar abscess (PTA) associated to NSAIDs consumption during a pharyngitis episode observed in primary care. Method A retrospective cohort study using Observatory of General Medicine Datalink from 1995 to 2010. All patients consulting a GP from the Datalink network for pharyngitis have been included. The occurrence of a PTA in the 15 days following the consultation for pharyngitis was matched. The association between PTA and prescriptions of NSAIDs was studied via an adjusted logistic regression model. Results During the study period, 105 802 cases of pharyngitis and 48 cases of PTA following a pharyngitis were reported, concerning respectively 67 765 and 47 patients. In the multivariate analysis, the risk of PTA was associated positively with a NSAIDs prescription (OR = 2.9, 95% CI = 1.6–5.2). Other factors associated with PTA occurrence were the prescription of corticosteroids (OR = 3.1, 95% CI = 1.3–7.6) and an age between 20 and 40 years (OR = 5.7, 95% CI = 2.5–13.0). The prescription of antibiotics was not significantly associated with PTA (P = 0.7). Conclusion Prescription of NSAIDs in pharyngitis may increase the risk of PTA. This study encourages considering cautiously the balance between benefits and harms before prescription of NSAIDs for pharyngitis.

An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied.To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest.A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018.Continuous PPI use during the 2015 to 2016 AGE winter epidemic.The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions.There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older.Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.

Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. In France, hyperendemic areas including Corsica have an anti-HEV Immunoglobulin G (IgG) prevalence higher than 50%. The aim of this study was to determine the seroprevalence of anti-HEV IgG in three adult populations in Corsica and the risk factors associated with antibody detection. Between 2017 and 2019, a total of 930 individuals, including 467 blood donors, 393 students or university staff members and 70 patients from general practice, were tested for the presence of anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay kit and filled a questionnaire. The association between seropositivity and potential risk factors was tested with univariate and multivariate analyses. Out of the 930 samples, 52.3% (486/930) were seropositive&mdash, 54.4% (254/467) among blood donors, 47.6% (187/393) among university students and 64.3% (45/70) among patients of general practice. Three main risk factors were identified: (i) skinning and butchering (Adjusted Odds Ratio aOR = 2.76, 95% confidence interval [95% CI] [1.51&ndash, 5.37], p-value &lt, 10&minus, 3), (ii) consumption of a local pork live raw sausage (fittonu) (aOR = 1.95 95% CI [1.45&ndash, 2.64], p-value = 10&minus, 5), and (iii) increasing age (p-value = 0.003). Seropositivity rates between the different populations were homogeneous after age stratification. This cross-sectional study indicates a high anti-HEV IgG seroprevalence in the Corsican adult population, not significantly different between women and men and increasing with age. This serosurvey also showed homogeneity regarding the exposure to HEV among three different types of populations. Finally, we confirmed the endemicity of Corsica with respect to HEV and identified a strong association between consumption of figatellu/fittonu and the practice of skinning and butchering with the detection of anti-HEV IgG.

International audience; Objectives: We aimed to identify patients' clinical characteristics associated with respiratory viruses identified among patients presenting with influenza-like illness (ILI).Methods: A sample of patients of all ages presenting with ILI was included by physicians of the French Sentinelles network during two seasons (2015/16 and 2016/17). Nasopharyngeal samples were tested for the presence of influenza virus (IV), respiratory syncytial virus (RSV), human rhinovirus (HRV) and human metapneumovirus (HMPV). Patients' characteristics associated with each of the four virus classes were studied using multivariate logistic regressions.Results: A total of 5859 individuals were included in the study: 48.0% tested positive for IV, 7.9% for HRV, 7.5% for RSV and 4.1% for HMPV. Cough was associated with IV (OR 2.14, 95% CI 1.81–2.52) RSV (OR 2.52, 95% CI 1.75–3.74) and HMPV detection (OR 2.15, 95% CI 1.40–3.45). Rhinorrhoea was associated mainly with HRV detection (OR 1.75, 95% CI 1.34–2.32). Headache was associated with IV detection (OR 1.75, 95% CI 1.34–2.32), whereas absence of headache was associated with RSV and HMPV detection. Dyspnoea was associated with RSV detection (OR 2.33, 95% CI 1.73–3.12) and absence of dyspnoea with IV detection. Conjunctivitis was associated with IV detection (OR 1.27, 95% CI 1.08–1.50). Some associations were observed only in children: dyspnoea and cough with RSV detection (age

Infections caused by Streptococcus pneumoniae —including invasive pneumococcal diseases (IPDs)—remain a significant public health concern worldwide. The marked winter seasonality of IPDs is a striking, but still enigmatic aspect of pneumococcal epidemiology in nontropical climates. Here we confronted age-structured dynamic models of carriage transmission and disease with detailed IPD incidence data to test a range of hypotheses about the components and the mechanisms of pneumococcal seasonality. We find that seasonal variations in climate, influenza-like illnesses, and interindividual contacts jointly explain IPD seasonality. We show that both the carriage acquisition rate and the invasion rate vary seasonally, acting in concert to generate the marked seasonality typical of IPDs. We also find evidence that influenza-like illnesses increase the invasion rate in an age-specific manner, with a more pronounced effect in the elderly than in other demographics. Finally, we quantify the potential impact of seasonally timed interventions, a type of control measures that exploit pneumococcal seasonality to help reduce IPDs. Our findings shed light on the epidemiology of pneumococcus and may have notable implications for the control of pneumococcal infections.

International audience; BACKGROUND:In a context of increasing use of Nucleic Acid Amplification Test, diagnoses of Neisseria gonorrhoeae and Chlamydia trachomatis infections among men increased in Europe and USA since 2007. We aimed to describe trends in the incidence of male urethritis in France between 2007 and 2017.METHODS:We analysed male urethritis clinical cases reported by the French GPs' Sentinelles network.RESULTS:GPs reported 1944 cases of male urethritis during the study period. The estimated annual incidence rates in men aged 15 years and older remained stable between 226 cases per 100,000 seen in 2007 and 196 in 2017 (P value = 0.9). A third-generation cephalosporin with macrolide or tetracycline was prescribed in 17.5% of cases in 2009 (27/154) and 32.4% in 2017 (47/145) (P value = 0.0327).CONCLUSIONS:The incidence rates for adult male urethritis diagnosed in primary care have remained stable since 2007 in France in contrast with the increasing trend of Neisseria gonorrhoeae and Chlamydia trachomatis infections based on microbiological surveillance. Using stable clinical definition for male urethritis seems essential to follow correctly epidemiological dynamic.

Introduction Participatory surveillance systems provide rich crowdsourced data, profiling individuals and their health status at a given time. We explored the usefulness of data from GrippeNet.fr, a participatory surveillance system, to estimate influenza-related illness incidence in France. Methods: GrippeNet.fr is an online cohort since 2012 averaging ca. 5,000 weekly participants reporting signs/symptoms suggestive of influenza. GrippeNet.fr has flexible criteria to define influenza-related illness. Different case definitions based on reported signs/symptoms and inclusions of criteria accounting for individuals’ reporting and participation were used to produce influenza-related illness incidence estimates, which were compared to those from sentinel networks. We focused on the 2012/13 and 2013/14 seasons when two sentinel networks, monitoring influenza-like-illness (ILI) and acute respiratory infections (ARI) existed in France. Results: GrippeNet.fr incidence estimates agreed well with official temporal trends, with a higher accuracy for ARI than ILI. The influenza epidemic peak was often anticipated by one week, despite irregular participation of individuals. The European Centre for Disease Prevention and Control ILI definition, commonly used by participatory surveillance in Europe, performed better in tracking ARI than ILI when applied to GrippeNet.fr data. Conclusion: Evaluation of the epidemic intensity from crowdsourced data requires epidemic and intensity threshold estimations from several consecutive seasons. The study provides a standardised analytical framework for crowdsourced surveillance showing high sensitivity in detecting influenza-related changes in the population. It contributes to improve the comparability of epidemics across seasons and with sentinel systems. In France, GrippeNet.fr may supplement the ILI sentinel network after ARI surveillance discontinuation in 2014.

International audience; The seasonalities of influenza-like illnesses (ILIs) and invasive pneumococcal diseases (IPDs) remain incompletely understood. Experimental evidence indicates that influenza-virus infection predisposes to pneumococcal disease, so that a correspondence in the seasonal patterns of ILIs and IPDs might exist at the population level. We developed a method to characterize seasonality by means of easily interpretable summary statistics of seasonal shape-or seasonal waveforms. Nonlinear mixed-effects models were used to estimate those waveforms based on weekly case reports of ILIs and IPDs in 5 regions spanning continental France from July 2000 to June 2014. We found high variability of ILI seasonality, with marked fluctuations of peak amplitudes and peak times, but a more conserved epidemic duration. In contrast, IPD seasonality was best modeled by a markedly regular seasonal baseline, punctuated by 2 winter peaks in late December to early January and January to February. Comparing ILI and IPD seasonal waveforms, we found indication of a small, positive correlation. Direct models regressing IPDs on ILIs provided comparable results, even though they estimated moderately larger associations. The method proposed is broadly applicable to diseases with unambiguous seasonality and is well-suited to analyze spatially or temporally grouped data, which are common in epidemiology.

International audience; Objectives: We discussed which method between the test-negative design (TND) and the screening method (SM) could provide more robust real-time and end-of-season vaccine effectiveness (VE) estimates using data collected from routine influenza surveillance in primary care. Methods: We used data collected during two influenza seasons, 2014e15 and 2015e16. Using the SM, we estimated end-of-season VE in preventing medically attended influenza-like illness and laboratory-confirmed influenza among the population at risk. Using the TND, we estimated end-of-season VE in preventing influenza among both the general and the at-risk population. We estimated real-time VE using both methods. Results: For the SM, the overall adjusted end-of-season VE was 24% (95% confidence interval (CI), 16 to 32) and 12% (95% CI, À16 to 33) during season 2014e15, and 53% (95% CI, 44 to 60) and 47% (95% CI, 23 to 64) during season 2015e16, in preventing influenza-like illness and laboratory-confirmed influenza, respectively. For the TND, the overall adjusted end-of-season VE was À17% (95% CI, À79 to 24) and À38% (95% CI, À199 to 13) in 2014e15, and 10% (95% CI, À31 to 39) and 18% (95% CI, À33 to 50) in 2015e16, among the general and at-risk population, respectively. Real-time VE estimates obtained through the TND showed more variability across each season and lower precision than those estimated with the SM. Conclusions: Although the worldwide use of the TND allows for comparison of overall VE estimates among countries, the SM performs better in providing robust real-time VE estimates among the population at risk. A.M. Vilcu, Clin Microbiol Infect 2018;24:431.e5e431.e12

SUMMARYInfluenza epidemics are monitored using influenza-like illness (ILI) data reported by health-care professionals. Timely detection of the onset of epidemics is often performed by applying a statistical method on weekly ILI incidence estimates with a large range of methods used worldwide. However, performance evaluation and comparison of these algorithms is hindered by: (1) the absence of a gold standard regarding influenza epidemic periods and (2) the absence of consensual evaluation criteria. As of now, performance evaluations metrics are based only on sensitivity, specificity and timeliness of detection, since definitions are not clear for time-repeated measurements such as weekly epidemic detection. We aimed to evaluate several epidemic detection methods by comparing their alerts to a gold standard determined by international expert consensus. We introduced new performance metrics that meet important objective of influenza surveillance in temperate countries: to detect accurately the start of the single epidemic period each year. Evaluations are presented using ILI incidence in France between 1995 and 2011. We found that the two performance metrics defined allowed discrimination between epidemic detection methods. In the context of performance detection evaluation, other metrics used commonly than the standard could better achieve the needs of real-time influenza surveillance.

International audience; Background: The ongoing 2016/17 influenza epidemic in France is characterized by the circulation of A(H3N2) viruses, known to cause more severe illness among at risk populations.Objectives: The purpose of our study was to provide early influenza vaccine effectiveness (IVE) estimates for the ongoing influenza epidemic in France and compare these estimates over the six post-pandemic IVE.Study design: We used clinical and virological data collected in primary care by the French Sentinelles network. IVE in preventing influenza infection was estimated by the test-negative design method. The screening method was used to estimate IVE in preventing medically-attended influenza-like illness among target groups (

Voir aussi dépôt du preprint : https://hal.archives-ouvertes.fr/hal-02562668v2; International audience; Surveillance data used by epidemic alert systems are typically fully aggregated in space at the national level. However, epidemics may be spatially heterogeneous, undergoing distinct dynamics in distinct regions of the surveillance area. We unveiled this in retrospective analyses by classifying incidence time series. We used Pearson correlation to quantify the similarity between local time series and then classified them using modularity maximization. The surveillance area was thus divided into regions with different incidence patterns. We analyzed 31 years (1985-2016) of data on influenza-like illness from the French Sentinelles system and found spatial heterogeneity in 19 of 31 influenza seasons. However, distinct epidemic regions could be identified only 4-5 weeks after a nationwide alert. The impact of spatial heterogeneity on influenza epidemiology was complex. First, when a nationwide alert was triggered, 32%-41% of the administrative regions of France were experiencing an epidemic, while the others were not. Second, the nationwide alert was timely for the whole surveillance area, but subsequently regions experienced distinct epidemic dynamics. Third, the epidemic dynamics were homogeneous in space. Spatial heterogeneity analyses can provide information on the timing of the peak and end of the epidemic, in various regions, for use in tailoring disease monitoring and control.

Is there a role for the screening method in estimating influenza vaccine effectiveness (VE)? The answer is yes, but the simplicity of the method used has raised concerns about its validity, and several cautions should be noted. The screening method provides an approximation of influenza VE by comparing the proportion of cases vaccinated (PCV) with the proportion of persons vaccinated (PPV) in the general population. This method has an important disadvantage: VE estimation could be inaccurate if the values for PCV and PPV are drawn from different populations, but it has an important strength, compared with other observational studies, in providing an early indication of VE in the field. Thus, when an infrastructure, such as routine surveillance, is in place to collect robust PCV values, and PPV can be obtained from routine vaccine uptake monitoring systems, the screening method can provide early estimates of influenza VE in target groups.

Purpose Anti-dopaminergic anti-emetics (ADA) use for the treatment of nausea associated with gastroenteritis (GE) can be considered inappropriate, as their effects are not supported by evidence of clinical efficacy and can potentially induce serious adverse events. Objective This study quantifies the suboptimal consumption of ADA attributable to seasonal GE epidemics in France and its cost. Methods GE epidemiological data were collected and transmitted by the general practitioners (GPs) of Sentinelles network. Epidemic periods were identified by periodic regression. Drug sales data were obtained from pharmacies, and costs data were obtained from the French National Social Security. The ADA use and costs incurred by seasonal GE epidemics were calculated. Results During the epidemic periods considered in this study, the median age of patients seen by GPs for GE was 24 years old. During each epidemic, a sale increase by 14% for domperidone, by 15% for metoclopramide and 30% for metopimazine was observed. The average cost attributable to seasonal GE epidemic was 5 030 000 Euros, of which 2 160 000 Euros were incurred by the French National Social Security. Conclusion Linking epidemiological databases helped to identify and quantify inappropriate ADA prescriptions. GE treatment guidelines should be disseminated more widely. Copyright © 2013 John Wiley & Sons, Ltd.

Background In surveillance networks based on voluntary participation of health-care professionals, there is little choice regarding the selection of participants’ characteristics. External information about participants, for example local physician density, can help reduce bias in incidence estimates reported by the surveillance network. Methods There is an inverse association between the number of reported influenza-like illness (ILI) cases and local general practitioners (GP) density. We formulated and compared estimates of ILI incidence using this relationship. To compare estimates, we simulated epidemics using a spatially explicit disease model and their observation by surveillance networks with different characteristics: random, maximum coverage, largest cities, etc. Results In the French practice-based surveillance network – the “Sentinelles” network – GPs reported 3.6% (95% CI [3;4]) less ILI cases as local GP density increased by 1 GP per 10,000 inhabitants. Incidence estimates varied markedly depending on scenarios for participant selection in surveillance. Yet accounting for change in GP density for participants allowed reducing bias. Applied on data from the Sentinelles network, changes in overall incidence ranged between 1.6 and 9.9%. Conclusions Local GP density is a simple measure that provides a way to reduce bias in estimating disease incidence in general practice. It can contribute to improving disease monitoring when it is not possible to choose the characteristics of participants. Electronic supplementary material The online version of this article (doi:10.1186/s12874-016-0260-x) contains supplementary material, which is available to authorized users.

Background Urinary tract infections (UTIs) are among the most common bacterial infections. Despite this burden, there are few studies of the costs of UTIs. The objective of this study was to determine the costs of UTIs in women over 18 years of age who visit general practitioners in France. Methods The direct and indirect costs of clinical UTIs were estimated from societal, French National Health Insurance and patient perspectives. The study population was derived from a national cross-sectional survey entitled the Drug-Resistant Urinary Tract Infection (Druti). The Druti included every woman over 18 years of age who presented with symptoms of UTI and was conducted in France in 2012 and 2013 to estimate the annual incidence of UTIs due to antibiotic-resistant Enterobacteriaceae in women visiting general practitioners (GPs) for suspected UTIs. Results Of the 538 women included in Druti, 460 were followed over 8 weeks and included in the cost analysis. The mean age of the women was 46 years old. The median cost of care for one episode of a suspected UTI was €38, and the mean cost was €70. The annual societal cost was €58 million, and €29 million of this was reimbursed by the French National Health Insurance system. In 25 % of the cases, the suspected UTIs were associated with negative urine cultures. The societal cost of these suspected UTIs with negative urine cultures was €13.5 million. No significant difference was found between the costs of the UTIs due to antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63). Conclusion In the current context in which the care costs are continually increasing, the results of this study suggests that it is possible to decrease the cost of UTIs by reducing the costs of suspected UTIs and unnecessary treatments, as well as limiting the use of non-recommended tests. Electronic supplementary material The online version of this article (doi:10.1186/s12913-016-1620-2) contains supplementary material, which is available to authorized users.

PURPOSE: In-patients characteristics generate cost differences between hospitals. In France, there are few data on the characteristics on the patients referred to hospitals by their general practitioners (GPs) and none on the predictors of referral to the public or for-profit hospitals. The aim of this study was to analyze those characteristics and the predictors of referral to the public or for-profit hospitals. METHODS: We collected, prospectively, the request for hospitalizations made by the GPs of the Sentinelles network in France, from 2007 to 2009. Patients' characteristics and also the reasons for that request were analyzed. A logistic regression was used to compare the population between local hospitals. RESULTS: Ten thousand seven hundred and eighteen statements were collected. The median age was 73 years. Patients were women in 51% of the cases, and only 14% of the hospitalizations had been planned. Hospitalization in the public sector was preferred for young children and the elderly (P

International audience; BACKGROUND: Varicella can be severe in adults. When universal vaccination is not adopted, post-exposure prophylaxis has been recommended in adults with uncertain history of varicella to reduce the burden of the disease in adults, however its impact is not quantified.METHODS:We developed a Bayesian probabilistic framework to estimate the impact of post-exposure prophylaxis in adults. We hypothesized that post-exposure vaccination would be proposed only after varicella exposure in close relatives. Information regarding the nature of the culprit exposure was obtained from a sample of 221 adult varicella cases. The lifelong probability that adults aged 18 would be infected with varicella was determined using data from the French Sentinelles surveillance network. Estimates of post-exposure vaccination efficacy were then used to compute the number of cases and hospitalizations prevented in adults.RESULTS:Familial exposure to varicella was reported by 81 adult cases out of 221. The probability of infection after exposure was 32%, so that six exposures on average were necessary to explain the observed cumulated lifetime incidence of varicella in non-immune 18 years old and over adults. Among the 35% of the 18 years old population with uncertain history of varicella, 11% would truly be non-immune. Post-exposure vaccination would prevent 26% of the cases (13 cases prevented per 100,000 adults per year) and 31% of the hospitalizations (0.2 hospitalizations prevented per 100,000 adults per year) if vaccination acceptance was 70%. An average of 16 adults would be vaccinated to avert one varicella case.CONCLUSIONS:Post-exposure vaccination is associated with a substantial decrease in the burden of the disease in adults in a country where universal vaccination is not recommended. This quantitative information may help inform professionals to uphold the recommendation.

Background Data describing the epidemiology and management of viral acute diarrhea (AD) in adults are scant. The objective of this study was to identify the incidence, clinical characteristics, management and risk factors of winter viral AD in adults. Methods The incidence of AD in adults during two consecutive winters (from December 2010 to April 2011 and from December 2011 to April 2012) was estimated from the French Sentinelles network. During these two winters, a subset of Sentinelles general practitioners (GPs) identified and included adult patients who presented with AD and who filled out a questionnaire and returned a stool specimen for virological examination. All stool specimens were tested for astrovirus, group A rotavirus, human enteric adenovirus, and norovirus of genogroup I and genogroup II. Age- and sex-matched controls were included to permit a case–control analysis with the aim of identifying risk factors for viral AD. Results During the studied winters, the average incidence of AD in adults was estimated to be 3,158 per 100,000 French adults (95% CI [2,321 – 3,997]). The most reported clinical signs were abdominal pain (91.1%), watery diarrhea (88.5%), and nausea (83.3%). GPs prescribed a treatment in 95% of the patients with AD, and 80% of the working patients with AD could not go to work. Stool examinations were positive for at least one enteric virus in 65% (95% CI [57 – 73]) of patients with AD with a predominance of noroviruses (49%). Having been in contact with a person who has suffered from AD in the last 7 days, whether within or outside the household, and having a job (or being a student) were risk factors significantly associated with acquiring viral AD. Conclusions During the winter, AD of viral origin is a frequent disease in adults, and noroviruses are most often the cause. No preventable risk factor was identified other than contact with a person with AD. Thus, at the present time, reinforcement of education related to hand hygiene remains the only way to reduce the burden of disease. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0574-4) contains supplementary material, which is available to authorized users.

International audience; Influenza-like illness (ILI) surveillance is important to identify circulating and emerging/reemerging strains and unusual epidemiological trends. The present study aimed to give an accurate picture of the 2012–2013 ILI outbreak in Corsica by combining data from several surveillance systems: general practice, emergency general practice, hospital emergency units, intensive care units, and nursing homes. Twenty-eight respiratory viruses were retrospectively investigated from patients in general practice with ILI. Sequence analysis of the genetic changes in the hemagglutinin gene of influenza viruses (A(H1N1)pdm2009, A(H3N2) and B) was performed. The trends in ILI/influenza consultation rates and the relative illness ratios (RIRs) of having an ILI consultation were estimated by age group for the different surveillance systems analyzed. Of the 182 ILI patients enrolled by general practitioners, 57.7% tested positive for influenza viruses. Phylogenetic analyses suggested a genetic drift for influenza B and A(H3N2) viruses. The ILI/influenza surveillance systems showed similar trends and were well correlated. In accordance with virological data, the RIRs of having an ILI consultation were highest among the young (,15 years old) and decreased with age. No clusters of acute respiratory illness were declared by the sentinel nursing homes. This study is noteworthy in that it is the first extensive description of the 2012–2013 ILI outbreak in Corsica as monitored through several surveillance systems. To improve ILI surveillance in Corsica, a consortium that links together the complementary regional surveillance ILI systems described here is being implemented.