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Background: Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies., Methods: Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI., Results: We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24-3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17-3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37-4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07-2.17; p = 0.026), diabetes (1.44, 95%CI 1.14-1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06-1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04-1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25-0.78; p < 0.001)., Conclusion: In the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone., (© 2024. The Author(s).)

Background: Recreational nitrous oxide (N 2 O) use has become more widespread worldwide, leading to an increase in myelopathies and peripheral neuropathies. The aim of this study was to describe clinical and socioeconomical characteristics of severe N 2 O-induced (NI) neurological disorders (NI-NDs), to determine its incidence in the Greater Paris area and to compare it with that of similar inflammatory neurological disorders., Methods: We performed a retrospective multicentric cohort study of all adult patients with severe NI-NDs in the neurology and general internal medicine departments of the Greater Paris area from 2018 to 2021. The incidence was compared with that of non-NI-myelitis and Guillain-Barré syndrome (GBS) using a sample of 91,000 hospitalized patients sourced from health insurance data., Results: Among 181 patients, 25% had myelopathy, 37% had peripheral neuropathy and 38% had mixed disease. Most were aged between 20 and 25 years, lived in socially disadvantaged urban areas, and exhibited high rates of unemployment (37%). The incidence of NI-NDs increased during 2020 and reached a peak mid-2021. The 2021 incidence in 20-25-year-olds was 6.15 [4.72; 8.24] per 100,000 persons for NI-myelopathy and 7.48 [5.59; 9.37] for NI-peripheral neuropathy. This was significantly higher than for non-NI-myelitis (0.35 [0.02; 2.00]) and GBS (2.47 [0.64; 4.30]). The incidence of NI-NDs was two to three times higher in the most socially disadvantaged areas., Conclusion: The recent increase in recreational N 2 O use has led to a rise in the incidence of severe NI-NDs, particularly in young adults with low socioeconomic status for whom NI-NDs strongly outweigh similar neurological disorders., (© 2024. The Author(s).)

Purpose: Pharmacokinetic interactions exist between apixaban or rivaroxaban, and CYP3A4 and P-glycoprotein inhibitors such as amiodarone, verapamil and diltiazem. We aimed to estimate the prevalence of exposure to this drug-drug association (DDA) and to assess the bleeding risk associated in patients with atrial fibrillation (AF)., Methods: We conducted a cohort study using a representative 1/97 th sample of the French healthcare insurance database between 2014 and 2019. Patients with AF receiving apixaban or rivaroxaban were included and followed-up until hospitalization for bleeding, death, discontinuation of apixaban or rivaroxaban, exposure to strong CYP3A4 inhibitor, or until December 31 st 2019, whichever came first. Primary outcome was hospitalization for bleeding registered as primary diagnosis. The association between the exposure to the DDA and hospitalization for bleeding was evaluated as a time-dependent variable in Cox model., Results: Between 2014 and 2019, the AF population under apixaban or rivaroxaban represented 10,392 patients. During the study period, the annual average prevalence of DDA exposure in this population was 38.9%. Among the 10,392 patients, 223 (2.1%) were hospitalized for bleeding, of which 75 (33.6%) received the association and 148 (66.4%) received apixaban or rivaroxaban alone. There was no association between DDA exposure and risk of hospitalization for bleeding (aHR = 1.19, [95% CI: 0.90, 1.58]). Age (HR 1.03 [1.02, 1.05]) and male gender (HR 1.72 [1.28, 2.30]) were associated with an increased risk of hospitalization for bleeding., Conclusion: Exposure to antiarrhythmic drugs was not associated with an increased risk of hospitalization for bleeding in patients with AF under rivaroxaban or apixaban., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Influenza-like illness (ILI) incidence estimates in individuals treated with immunosuppressants and/or biologics and/or corticosteroid for an autoimmune or chronic inflammatory disease are scarce. We compared the ILI incidence among immunocompromised population and the general population., Method: We conducted a prospective cohort study during the 2017-2018 seasonal influenza epidemic, on the GrippeNet.fr electronic platform, which allows the collection of epidemiological crowdsourced data on ILI, directly from the French general population. The immunocompromised population were adults treated with systemic corticosteroids, immunosuppressants, and/or biologics for an autoimmune or chronic inflammatory disease, recruited directly on GrippeNet.fr and also among patients of the departments of a single university hospital that were asked to incorporate GrippeNet.fr. The general population consisted of adults reporting none of the above treatments or diseases participating in GrippeNet.fr. The incidence of ILI was estimated on a weekly basis and compared between the immunocompromised population and the general population, during the seasonal influenza epidemic., Results: Among the 318 immunocompromised patients assessed for eligibility, 177 were included. During the 2017-2018 seasonal influenza epidemic period, immunocompromised population had 1.59 (95% CI: 1.13-2.20) higher odds to experience an ILI episode, compared to the general population (N = 5358). An influenza vaccination was reported by 58% of the immunocompromised population, compared to 41% of the general population (p < 0.001)., Conclusion: During a seasonal influenza epidemic period, the incidence of influenza-like illness was higher in patients treated with immunosuppressants, biologics, and/or corticosteroids for an autoimmune or chronic inflammatory disease, compared to the general population., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE)., Methods: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions., Results: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2., Discussion: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Purpose: This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants., Methods: This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists., Results: A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001]., Conclusion: This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March-September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced.

We aimed to investigate the immunoglobulin G response and neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among primary health care workers (PHCW) in France and assess the association between the neutralizing activity and several factors, including the coronavirus disease 2019 (COVID-19) vaccination scheme. A cross-sectional survey was conducted between 10 May 2021 and 31 August 2021. Participants underwent capillary blood sampling and completed a questionnaire. Sera were tested for the presence of antibodies against the nucleocapsid (N) protein and the S-1 portion of the spike (S) protein and neutralizing antibodies. In total, 1612 PHCW were included. The overall seroprevalences were: 23.6% (95% confidence interval (CI) 21.6-25.7%) for antibodies against the N protein, 94.7% (93.6-95.7%) for antibodies against the S protein, and 81.3% (79.4-83.2%) for neutralizing antibodies. Multivariate regression analyses showed that detection of neutralizing antibodies was significantly more likely in PHCW with previous SARS-CoV-2 infection than in those with no such history among the unvaccinated (odds ratio (OR) 16.57, 95% CI 5.96-59.36) and those vaccinated with one vaccine dose (OR 41.66, 95% CI 16.05-120.78). Among PHCW vaccinated with two vaccine doses, the detection of neutralizing antibodies was not significantly associated with previous SARS-CoV-2 infection (OR 1.31, 95% CI 0.86-2.07), but was more likely in those that received their second vaccine dose within the three months before study entry than in those vaccinated more than three months earlier (OR 5.28, 95% CI 3.51-8.23). This study highlights that previous SARS-CoV-2 infection and the time since vaccination should be considered when planning booster doses and the design of COVID-19 vaccine strategies.

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 a unidirectional case-crossover study using the EGB (Échantillon généraliste de bénéficiaires), 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 before hospital admission to 3 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 (ORs). 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 nongastrointestinal 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 nongastrointestinal 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., (© 2021, The American College of Clinical Pharmacology.)

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

Objectives: Herpes zoster (HZ) exposes to alterations of the quality-of-life. HZ is more frequent in immunocompromised individuals, but whether immunosuppression is associated with a higher rate of complications is not well documented. We aimed to assess association between drug-induced immunosuppression and HZ complications., Methods: Data from a sample of the French healthcare claims from 01/01/2006 to 12/31/2018 were analyzed. Complicated zoster (CZ) was defined as a hospitalization with a code for HZ or the first-time dispensation of high-dose valacyclovir and specific neuralgia analgesics. Drug-induced immunosuppression was identified through medication dispensation. Risk ratios were calculated to compare incidences in exposed individuals (EI) and non-exposed to immunosuppressive therapy (NEI)., Results: We identified 227 and 2838 CZ, accounting for an incidence of 178 per 100,000 person-year (95%CI[154.9-201.1]) and 51.7 per 100,000 person-year (95%CI[49.8-53.6]), in EI and NEI, respectively (risk ratio: 3.44 (95%CI[3.01-3.94]). Mean age was 66 years in both groups. CZ occurred after a median of 11.7 months (IQR[5.3-49.9]) of immunosuppressive therapy. Post-herpetic neuralgia (PHN) lasted at least 3 months in 32.6% and 22.5% of cases in EI and NEI, respectively (p=.01)., Conclusions: Drug-induced immunosuppression increases the risk of CZ and exposes to longer-lasting PHN. Figures provided in this study could help guide prophylaxis of HZ., Competing Interests: Declaration of competing interest The authors have no conflict nor link or interest to declare with regards to that work., (Copyright © 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: The knowledge of risk perceptions in primary care could help health authorities to manage epidemics., Methods: A 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., Results: A 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])., Conclusions: Regarding 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., (© 2022. The Author(s).)

During the COVID-19 pandemic, several generic variants emerged, including the Alpha variant, with increased transmissibility compared to historical strains. We aimed to compare the evolution of the viral load between patients infected with the Alpha variant and those infected with the historical SARS-CoV-2 strains, while taking into account the time interval between the onset of symptoms and samples. We used data collected from patients with an acute respiratory infection (mild to moderate symptoms) and seen in consultation in primary care, included in a prospective longitudinal study, COVID-A. Patients performed four salivary samples during the follow-up. All patients who had at least one of the saliva samples test positive for SARS-CoV-2 were included in the analysis. Overall, 118 patients were included: 89 infected by the historical strain and 29 infected by the Alpha variant. Even though we tended to observe a higher viral load in the Alpha variant group, we found no significant difference in the evolution of the viral load in saliva samples between patients infected with the Alpha variant of the SARS-CoV-2 and those infected by historical strains when controlling for the time interval between the onset of symptoms and sampling.

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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: ML and IB are employees of IQVIA France. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

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.

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45-74) for one dose only and 89% (95% CI: 79-94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.

Background: Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019-20 influenza vaccination and COVID-19., Methods: We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March to August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019-20 influenza vaccination and clinical information documented. Using logistic regression, we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with <15% of missing influenza vaccination. In secondary analyses, we included five countries, using multiple imputation with chained equations to account for missing data., Results: We included 257 COVID-19 cases and 1631 controls in the main analysis (three countries). The overall aOR between influenza vaccination and COVID-19 was 0.93 (95% CI: 0.66-1.32). The aOR was 0.92 (95% CI: 0.58-1.46) and 0.92 (95% CI: 0.51-1.67) among those aged 20-59 and ≥60 years, respectively. In secondary analyses, we included 6457 cases and 69 272 controls. The imputed aOR was 0.87 (95% CI: 0.79-0.95) among all ages and any delay between swab and symptom onset., Conclusions: There was no evidence that COVID-19 cases were more likely to be vaccinated against influenza than controls. Influenza vaccination should be encouraged among target groups for vaccination. I-MOVE-COVID-19 will continue documenting influenza vaccination status in 2020-21, in order to learn about effects of recent influenza vaccination., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: The present study was set up to evaluate the efficacy of virological surveillance using posterior oropharyngeal saliva samples to monitor the COVID-19 pandemic in general practice., Methods: Posterior oropharyngeal saliva samples were collected without restriction on timing or alimentation by general practitioners from patients with acute respiratory infection (ARI) seen in consultation. Saliva samples were tested by real-time reverse transcription polymerase chain reaction for SARS-CoV-2 and 21 other respiratory pathogens. Results for SARS-CoV-2 in saliva samples were compared to results obtained using a nasopharyngeal swab (NPS) collected in a certified medical laboratory before or after the ARI consultation., Results: Overall, 143 ARI patients were enrolled between 6 June 2020, and 19 January 2021. SARS-CoV-2 RNA was detected in 37.0% (n = 53) of saliva samples and in 39.0% (n = 56) of NPS. Both saliva and NPS were positive in 51 patients. Positive and negative results were concordant between saliva samples and NPS in 51 (96.2%) and in 85 (94.4%) patients, respectively, with a Cohen's Kappa coefficient of 0.89 (95% CI 0.82-0.97, p < 0.001). Other respiratory viruses were detected in 28.0% (n = 40) of the 143 saliva samples., Conclusions: Findings suggest that saliva samples could represent an attractive alternative to NPS for surveillance of SARS-CoV-2 in patients consulting for an ARI in primary care.

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.

IntroductionInfluenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE).AimThe I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort.MethodsWe measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0-14, 15-64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32-54-year-olds (1964-86) sharing potential childhood imprinting to serine at haemagglutinin position 159.ResultsInfluenza A(H3N2) VE among all ages was -1% (95% confidence interval (CI): -24 to 18) and 46% (95% CI: 8-68), -26% (95% CI: -66 to 4) and 20% (95% CI: -20 to 46) among 0-14, 15-64 and ≥ 65-year-olds, respectively. Among 15-64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: -34 to 50) and -74% (95% CI: -259 to 16), respectively. VE was -18% (95% CI: -140 to 41), -53% (95% CI: -131 to -2) and -12% (95% CI: -74 to 28) among 15-31-year-olds (1987-2003), 32-54-year-olds (1964-86) and 55-64-year-olds (1954-63), respectively.DiscussionThe lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964-86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15-64-year-olds and the public health impact of the I-REV hypothesis warrant further study.

Importance: 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., Objective: To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest., Design, Setting, and Participants: 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., Exposure: Continuous PPI use during the 2015 to 2016 AGE winter epidemic., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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.

Introduction: Influenza A(H3N2) viruses predominated in Europe in 2016-17. In 2017-18 A(H3N2) and A(H1N1)pdm09 viruses co-circulated. The A(H3N2) vaccine component was the same in both seasons; while the A(H1N1)pdm09 component changed in 2017-18. In both seasons, vaccine seed A(H3N2) viruses developed adaptations/alterations during propagation in eggs, impacting antigenicity., Methods: We used the test-negative design in a multicentre primary care case-control study in 12 European countries to measure 2016-17 and 2017-18 influenza vaccine effectiveness (VE) against laboratory-confirmed influenza A(H1N1)pdm09 and A(H3N2) overall and by age group., Results: During the 2017-18 season, the overall VE against influenza A(H1N1)pdm09 was 59% (95% CI: 47-69). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 64% (95% CI: 37-79), 50% (95% CI: 28-66) and 66% (95% CI: 42-80), respectively. Overall VE against influenza A(H3N2) was 28% (95% CI: 17-38) in 2016-17 and 13% (95% CI: -15 to 34) in 2017-18. Among 0-14-year-olds VE against A(H3N2) was 28% (95%CI: -10 to 53) and 29% (95% CI: -87 to 73), among 15-64-year-olds 34% (95% CI: 18-46) and 33% (95% CI: -3 to 56) and among those aged ≥65 years 15% (95% CI: -10 to 34) and -9% (95% CI: -74 to 32) in 2016-17 and 2017-18, respectively., Conclusions: Our study suggests the new A(H1N1)pdm09 vaccine component conferred good protection against circulating strains, while VE against A(H3N2) was <35% in 2016-17 and 2017-18. The egg propagation derived antigenic mismatch of the vaccine seed virus with circulating strains may have contributed to this low effectiveness. A(H3N2) seed viruses for vaccines in subsequent seasons may be subject to the same adaptations; in years with lower than expected VE, recommendations of preventive measures other than vaccination should be given in a timely manner., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Authors.)

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 <5 years), conjunctivitis with IV detection (age <15 years). Period of onset of symptoms differed among aetiological diagnoses. Seasonal influenza vaccination decreased the risk of IV detection (OR, 0.67, 95% CI 0.51-0.86)., Conclusions: This study allowed the identification of symptoms associated with several viral aetiologies in patients with ILI. A proper knowledge and understanding of these clinical signs may improve the medical management of patients., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: This study compares an algorithm to detect acute gastroenteritis (AG) episodes from drug dispensing data to the validated data reported in a primary care surveillance system in France., Methods: We used drug dispensing data collected in a drugstore database and data collected by primary care physicians involved in a French surveillance network, from season 2014/15 to 2016/17. We used an adapted version of an AG discrimination algorithm to identify AG episodes from the drugstore database. We used Pearson's correlation coefficient to evaluate the agreement between weekly AG signals obtained from the two data sources during winter months, in the overall population, by specific age-groups and by regions., Results: Correlations between AG signals for all ages were 0.84 [95%CI 0.69; 0.92] for season 2014/15, 0.87 [95%CI 0.75; 0.93] for season 2015/16 and 0.94 [95%CI 0.88; 0.97] for season 2016/17. The association between AG signals estimated from two data sources varied significantly across age groups in season 2016/17 (p-value < 0.01), and across regions in all three seasons studied (p-value < 0.01)., Conclusions: There is a strong agreement between the dynamic of AG activity estimated from drug dispensing data and from validated primary care surveillance data collected during winter months in the overall population but the agreement is poorer in several age groups and in several regions. Once automated, the reuse of drug dispensing data, already collected for reimbursement purposes, could be a cost-efficient method to monitor AG activity at the national level.

Background: Epidemiological analysis of past influenza epidemics remains essential to understand the evolution of the disease and optimize control and prevention strategies. Here, we aimed to use data collected by a primary care surveillance system over the last three decades to study trends in influenza epidemics and describe epidemic profiles according to circulating influenza viruses., Methods: Influenza-like illness (ILI) weekly incidences were estimated using cases reported by general practitioners participating in the French Sentinelles network, between 1984 and 2017. Influenza epidemics were detected by applying a periodic regression to this time series. Epidemic (co-)dominant influenza virus (sub)types were determined using French virology data., Results: During the study period, 297 607 ILI cases were reported allowing the detection of 33 influenza epidemics. On average, seasonal epidemics lasted 9 weeks and affected 4.1% of the population (95% CI 3.5; 4.7). Mean age of cases was 29 years. Epidemic size decreased over time by -66 cases per 100 000 population per season on average (95% CI -132; -0.2, P value = 0.049) and epidemic height decreased by -15 cases per 100 000 (95% CI -28; -2, P value = 0.022). Epidemic duration appeared stable over time. Epidemics were mostly dominated by A(H3N2) (n = 17, 52%), associated with larger epidemic size, higher epidemic peak and older age of cases., Conclusions: The declining trend in influenza epidemic size and height over the last 33 years might be related to several factors like increased vaccine coverage, hygiene improvements or changing in influenza viruses. However, further researches are needed to assess the impact of potential contributing factors to adapt influenza plans., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent., Objectives: To explore previous influenza vaccination effects on current season VE among population targeted for vaccination., Methods: We used 2011/2012 to 2016/2017 I-MOVE primary care multicentre test-negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only., Results: We included 941, 2645 and 959 influenza-like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were -68%, -21% and -19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%)., Conclusions: We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine., Methods: We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group., Results: We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively., Conclusions: Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine., (© 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

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, 2014-15 and 2015-16. 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, -16 to 33) during season 2014-15, and 53% (95% CI, 44 to 60) and 47% (95% CI, 23 to 64) during season 2015-16, in preventing influenza-like illness and laboratory-confirmed influenza, respectively. For the TND, the overall adjusted end-of-season VE was -17% (95% CI, -79 to 24) and -38% (95% CI, -199 to 13) in 2014-15, and 10% (95% CI, -31 to 39) and 18% (95% CI, -33 to 50) in 2015-16, 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., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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 (<65year with chronic diseases and ≥65 years) since 2010/11 influenza epidemic., Results: Early IVE estimates in primary care against influenza A(H3N2) were 48% (95% confidence interval (CI): 22-66) overall and 39% (95% CI: -17 to 69) among elderly (aged 65 and older). In comparison to the last six epidemics, 2016/17 early IVE in preventing influenza-like illness among target groups showed VE estimates higher to those reported during the 2011/12 and 2014/15 epidemics., Conclusions: The moderate 2016/17 IVE estimates were higher than those estimated during influenza A(H3N2) epidemics with vaccine mismatch., (Copyright © 2017 Elsevier B.V. All rights reserved.)