title: Impact of Outpatient Neuraminidase Inhibitor Treatment in Patients Infected With Influenza A(H1N1)pdm09 at High Risk of Hospitalization: An Individual Participant Data Metaanalysis.
abstract: BACKGROUND
  While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established. We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection.
  
  
  METHODS
  We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010. We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization. We adjusted for NAI treatment propensity and preadmission antibiotic use, including "study center" as a random intercept to account for differences in baseline hospitalization rate between centers.
  
  
  RESULTS
  We included 3376 patients with influenza A(H1N1)pdm09, of whom 3085 (91.4%) had laboratory-confirmed infection. Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%). After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20-0.30).
  
  
  CONCLUSIONS
  In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission. These data suggest that community patients with severe influenza should receive NAI treatment.
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, and.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Venkatesan
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, and.
authors.forename: Puja R
authors.initials: PR
authors.lastname: Myles
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, and.
authors.forename: Jo
authors.initials: J
authors.lastname: Leonardi-Bee
authors.affiliation: MRC Unit for Lifelong Health and Ageing, University College London, United Kingdom.
authors.forename: Stella G
authors.initials: SG
authors.lastname: Muthuri
authors.affiliation: Ministry of Health, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Malak
authors.initials: M
authors.lastname: Al Masri
authors.affiliation: Public Health England, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.affiliation: Department of Infection Control, Hospital San Martín de Paraná, Entre Ríos, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bantar
authors.affiliation: Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Dubnov-Raz
authors.affiliation: Pôle Femme Mère Enfant, Centre Hospitalier Universitaire de la Réunion.|Institut National de la Santé et de la Recherche Médical (INSERM) Centre for Clinical Investigation (CIC1410), Centre Hospitalier Universitaire de la Réunion, Saint Pierre.|Unité Mixte 134 PIMIT "Processus Infectieux en Milieu Insulaire Tropical" (Centre National de la Recherche Scientifique 9192, INSERM U1187, Institut Recherche et Développement 249), Université de la Réunion, CYROI "Cyclotron Réunion-océan Indien", Sainte Clotilde, Reunion.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gérardin
authors.affiliation: Molecular Diagnostic Centre, Department of Laboratory Medicine National University Hospital, and.|Department of Pathology, National University of Singapore.
authors.forename: Evelyn S C
authors.initials: ESC
authors.lastname: Koay
authors.affiliation: Molecular Diagnostic Centre, Department of Laboratory Medicine National University Hospital, and.
authors.forename: Tze Ping
authors.initials: TP
authors.lastname: Loh
authors.affiliation: Ministry of Health, Riyadh, Kingdom of Saudi Arabia.|College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Memish
authors.affiliation: Public Health England, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Infection Control, Hospital San Martín de Paraná, Entre Ríos, Argentina.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Oliva
authors.affiliation: Department of Pediatrics, Charité University Medical Center, and.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Rath
authors.affiliation: National Reference Centre Influenza at Robert Koch Institute, Berlin, Germany.
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Schweiger
authors.affiliation: Molecular Diagnostic Centre, Department of Laboratory Medicine National University Hospital, and.|University Hospitals Leicester, and.|Department of Infection, Immunity and Inflammation, University of Leicester, United Kingdom.
authors.forename: Julian W
authors.initials: JW
authors.lastname: Tang
authors.affiliation: Division of Infectious Diseases, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Canada.
authors.forename: Dat
authors.initials: D
authors.lastname: Tran
authors.affiliation: General Hospital Slovenj Gradec, Slovenia.
authors.forename: Tjasa
authors.initials: T
authors.lastname: Vidmar
authors.affiliation: Public Health England, United Kingdom.
authors.forename: Pauline A
authors.initials: PA
authors.lastname: Waight
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, and.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Nguyen-Van-Tam
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006760:Hospitalization; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D016017:Odds Ratio; D010045:Outpatients; D012044:Regression Analysis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009439:Neuraminidase
keywords: hospitalization; individual participant data metaanalyses; influenza; neuraminidase inhibitors; pandemic.