title: Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients.
abstract: We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza.  Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008-2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19-0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52-3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23-0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12-0.32), but there was benefit with treatment within 3-5 days (adjusted HR 0.35, 95% CI 0.21-0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27-0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14-2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered.
authors.affiliation: Dept of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China. leelsn@cuhk.edu.hk.
authors.forename: Nelson
authors.initials: N
authors.lastname: Lee
authors.affiliation: Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Dept of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China. Dept of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
authors.affiliation: Communicable Diseases Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: W M
authors.initials: WM
authors.lastname: Kyaw
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Uyeki
authors.affiliation: School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wilson W S
authors.initials: WW
authors.lastname: Tam
authors.affiliation: Dept of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Catherine S K
authors.initials: CS
authors.lastname: Cheung
authors.affiliation: Dept of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Irene M H
authors.initials: IM
authors.lastname: Yung
authors.affiliation: Dept of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Dept of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gu
authors.affiliation: Dept of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Dept of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Zhenjia
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Dept of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Jiuxin
authors.initials: J
authors.lastname: Qu
authors.affiliation: Dept of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: David S C
authors.initials: DS
authors.lastname: Hui
mesh_terms: D000146:Acids, Carbocyclic; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068476:Beijing / Q000453:epidemiology; D015331:Cohort Studies; D003517:Cyclopentanes / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007251:Influenza, Human / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000453:epidemiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D065840:Protective Factors; D012131:Respiratory Insufficiency / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D015163:Superinfection / Q000453:epidemiology*; D055815:Young Adult; D053243:Zanamivir / Q000627:therapeutic use
chemical_list: D000146:Acids, Carbocyclic; D000305:Adrenal Cortex Hormones; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir