title: The association between benzodiazepines and influenza-like illness-related pneumonia and mortality: a survival analysis using UK Primary Care data.
abstract: Bacterial superinfections, including pneumonia, are frequent complications of influenza-like illness (ILI). Clinical and laboratory evidence suggests that benzodiazepines and Z-drugs may influence susceptibility to infections and mortality. We investigated whether benzodiazepines and zopiclone modify the occurrence of ILI-related pneumonia and mortality.
  
  
  
  We obtained data on 804 051 ILI patients from a comprehensive primary care database, the Clinical Practice Research Datalink. The follow-up period started from the diagnosis of ILI for 30 days. Pneumonia and deaths occurring within the 30-day follow-up period were considered as potentially 'ILI related'. Exposure to benzodiazepines and zopiclone was determined in the period preceding a diagnosis of ILI with current use defined as a prescription for benzodiazepines in the month prior to ILI diagnosis. Cox regression was used for the analyses. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) are presented.
  
  
  
  Influenza-like illness-related pneumonia and mortality were noted in 1117 and 707 ILI patients, respectively. Current exposure to benzodiazepines was associated with increased occurrence of both ILI-related pneumonia and mortality (ILI-related pneumonia adjusted HR 4.24, 95%CI [2.27, 7.95]; ILI-related mortality adjusted HR 20.69, 95%CI [15.54, 27.54]). A similar increase in ILI-related mortality but not pneumonia was observed with current zopiclone use (ILI-related mortality adjusted HR 10.86, 95%CI [6.93, 17.02]; ILI-related pneumonia adjusted HR 1.97, 95%CI [0.63, 6.12]).
  
  
  
  Benzodiazepines may increase the likelihood of pneumonia and mortality related to ILI. A cautionary approach to prescribing benzodiazepine is suggested in people known to be at increased risk of pneumonia or mortality. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK. mcxgn@nottingham.ac.uk.
authors.forename: Georgina
authors.initials: G
authors.lastname: Nakafero
authors.affiliation: Department of Anaesthesiology, University of Wisconsin, Madison, WI, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sanders
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Nguyen-Van-Tam
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors.forename: Puja R
authors.initials: PR
authors.lastname: Myles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects; D001424:Bacterial Infections / Q000209:etiology* / Q000401:mortality; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D007251:Influenza, Human / Q000150:complications / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011014:Pneumonia / Q000209:etiology* / Q000401:mortality; D011320:Primary Health Care; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015163:Superinfection / Q000209:etiology* / Q000401:mortality; D016019:Survival Analysis; D006113:United Kingdom; D055815:Young Adult
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D001569:Benzodiazepines
keywords: benzodiazepines; influenza-like illness; mortality; pharmacoepidemiology; pneumonia; zopiclone