Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021-2022 I-MOVE primary care multicentre study

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.This project has received funding from the European Centre for Disease Prevention and Control with in the framework contract ECDC/2018/029.S

multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021

Funding Information: This project received funding from the European Centre for Disease Prevention and Control (ECDC) under the contract ECD.11486. Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673. Publisher Copyright: © 2022 European Centre for Disease Prevention and Control (ECDC). All rights reserved.Introduction: In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. Aim: Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection. Methods: Individuals 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. Results: Overall 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. Conclusions: VE 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.publishersversionpublishe

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021

I-MOVE-COVID-19 primary care study team (in addition to authors above): Nick Andrews, Jamie Lopez Bernal, Heather Whitaker, Caroline Guerrisi, Titouan Launay, Shirley Masse, Sylvie van der Werf, Vincent Enouf, John Cuddihy, Adele McKenna, Michael Joyce, Cillian de Gascun, Joanne Moran, Ana Miqueleiz, Ana Navascués, Camino Trobajo-Sanmartín, Carmen Ezpeleta, Paula López Moreno, Javier Gorricho, Eva Ardanaz, Fernando Baigorria, Aurelio Barricarte, Enrique de la Cruz, Nerea Egüés, Manuel García Cenoz, Marcela Guevara, Conchi Moreno-Iribas, Carmen Sayón, Verónica Gomez, Baltazar Nunes, Rita Roquete, Adriana Silva, Aryse Melo, Inês Costa, Nuno Verdasca, Patrícia Conde, Diogo FP Marques, Anna Molesworth, Leanne Quinn, Miranda Leyton, Selin Campbell, Janine Thoulass, Jim McMenamin, Ana Martínez Mateo, Luca Basile, Daniel Castrillejo, Carmen Quiñones Rubio, Concepción Delgado-Sanz, Jesús Oliva.The I-MOVE-COVID-19 network collates epidemiological and clinical information on patients with coronavirus disease (COVID-19), including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virological characterisation in 11 European countries [1]. One component of I-MOVE-COVID-19 is the multicentre vaccine effectiveness (VE) study at primary care/outpatient level in nine European study sites in eight countries. We measured overall and product-specific COVID-19 VE against symptomatic SARS-CoV-2 infection among those aged 65 years and older. We also measured VE by time since vaccination.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673.info:eu-repo/semantics/publishedVersio

Use of drug dispensing data for the identification and quantification of adverse effects associated with the consumption of prescribed drugs in ambulatory settings

Développées principalement comme un outil comptable, sur le fond du progrès informatique et des évolutions réglementaires, nous assistons à une intensification de l’utilisation secondaire des bases de données administratives pour la recherche dans le domaine de la santé, y compris des bases de données de délivrances des médicaments prescrits. Actuellement, les champs d’utilisation de ce type de données sont multiples, touchant aux domaines de l’épidémiologie, de la pharmaco-épidémiologie et de la pharmacovigilance. Les choix méthodologiques requis sont également nombreux et varient en fonction de la structure des bases de données utilisées et de la question de recherche. Dans cette thèse, on s’intéressera à l’utilisation des bases de données de délivrances des médicaments pour l’étude des effets indésirables associés à la consommation des médicaments prescrits en milieu extrahospitalier. Nous présentons d’abord une mise au point sur les bases de données administratives actuellement disponibles au niveau mondial et en France, leurs champs d’utilisation dans la recherche dans le domaine de la santé, et les principales approches méthodologiques envisageables. Les travaux réalisés dans le cadre de cette thèse présentent une illustration d’approche méthodologique concernant l’utilisation de ce type de base de données pour étudier l’association entre la consommation chronique d’un médicament largement prescrit en médecine extrahospitalière - les inhibiteurs de la pompe à protons (IPP), et la survenue d’un événement de santé aigu - la gastroentérite hivernale. Nous avons pour cela utilisé une base de données des délivrances de médicaments effectuées dans plus d’un tiers des pharmacies de ville situées en France métropolitaine. Le premier travail a consisté dans la validation d’un algorithme d’identification des cas de gastroentérite aigüe à partir des données de délivrances des médicaments prescrits, lorsqu’il est appliqué sur une base de données autre que celle sur laquelle il a été construit. Dans un deuxième travail, en utilisant cet algorithme, nous avons mis en évidence une association entre la survenue de gastroentérite en période hivernale et la prise continue d’IPP. Ces travaux illustrent la complexité des choix méthodologiques qui s’imposent lorsqu’un utilise des bases de données de délivrances des médicaments pour étudier les effets indésirables des médicaments.Although initially developed as an accounting tool, against the backdrop of computer progress and regulatory developments over the last decades, we are witnessing an increase in the secondary use of administrative databases for health research, including that of drug dispensing databases. Nowadays, this type of data sources is used in multiple health research fields, including epidemiology, pharmaco-epidemiology, and pharmacovigilance. The methodological choices required are also numerous and vary according to the structure of the databases used and the research question.This thesis will focus on the use of drug dispensing databases for the study of adverse drug reactions associated with the use of drugs prescribed in outpatient settings. We first present an overview of the administrative databases currently available worldwide and in France, their fields of use in health research, and the main methodological approaches. The work carried out within this thesis presents an illustration of a methodological approach concerning the use of this type of databases to study the association between the continuous consumption of a drug class widely prescribed in ambulatory care - proton pump inhibitors (PPIs) - and the occurrence of an acute health event - winter gastroenteritis. For this purpose, we used a database collecting drug dispensing data from more than a third of community pharmacies located in continental France. The first work consisted of the validation of an algorithm identifying acute gastroenteritis episodes based on prescription data when applied to a database other than that on which it was built. In a second work, using this algorithm, we investigated the association between the occurrence of gastroenteritis in the winter period and the continuous use of PPIs. This work illustrates the complexity of the methodological choices involved when using drug dispensing databases to study adverse drug reactions

Use of tramadol and the risk of bleeding complications in patients on oral anticoagulants: A systematic review and meta-analysis

International audiencePurpose 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 metaanalysis 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

Cross-validation of an algorithm detecting acute gastroenteritis episodes from prescribed drug dispensing data in France: comparison with clinical data reported in a primary care surveillance system, winter seasons 2014/15 to 2016/17

International audienceBackground: 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

Incidence of complications of herpes zoster in individuals on immunosuppressive therapy: A register-based population study

International audienceObjectives: 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

EX VIVO LIVER RESECTION FOR TUMORAL PATHOLOGY – BENEFITS, RISKS AND OUTCOMES

Ex vivo liver surgery techniques have been proposed almost two decades ago in order to extend the indications and feasibility of liver resections for large, but not absolutely unresectable liver lesions. However, the procedure remains a demanding one, being associated with high risks of postoperative complications; therefore it should be performed only in specialized centers. This is a literature review of the largest studies conducted on the theme of ex vivo liver resection for tumoral pathology

Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

International audienceImportance: 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

Bisphosphonate Use and Hospitalization for Hip Fractures in Women: An Observational Population-Based Study in France

International audienceBisphosphonates 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