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Summary
Background
Neuraminidase inhibitors were widely used during the 2009?10 influenza A H1N1 pandemic, but
evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant
data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to
hospital with pandemic influenza A H1N1pdm09 virus infection.
Methods
We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically
diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier
systematic review of reported studies addressing the same research question. In our systematic review, eligible studies
were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of
the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did
a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and
mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised
linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression
shared frailty modelling.
Findings
We included data for 29
234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and
March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated
with a reduction in mortality risk (adjusted odds ratio [OR] 0?81; 95% CI 0?70?0?93; p=0?0024). Compared with later
treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted
OR 0?48; 95% CI 0?41?0?56; p<0?0001). Early treatment versus no treatment was also associated with a reduction in
mortality (adjusted OR 0?50; 95% CI 0?37?0?67; p<0?0001). These associations with reduced mortality risk were less
pronounced and not significant in children. There was an increase in the mortality hazard rate with each day?s delay in
initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard
ratio [HR 1?23] [95% CI 1?18?1?28]; p<0?0001 for the increasing HR with each day?s delay).
Interpretation
We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with
suspected or proven influenza infection.
full article
Background
Neuraminidase inhibitors were widely used during the 2009?10 influenza A H1N1 pandemic, but
evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant
data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to
hospital with pandemic influenza A H1N1pdm09 virus infection.
Methods
We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically
diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier
systematic review of reported studies addressing the same research question. In our systematic review, eligible studies
were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of
the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did
a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and
mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised
linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression
shared frailty modelling.
Findings
We included data for 29
234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and
March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated
with a reduction in mortality risk (adjusted odds ratio [OR] 0?81; 95% CI 0?70?0?93; p=0?0024). Compared with later
treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted
OR 0?48; 95% CI 0?41?0?56; p<0?0001). Early treatment versus no treatment was also associated with a reduction in
mortality (adjusted OR 0?50; 95% CI 0?37?0?67; p<0?0001). These associations with reduced mortality risk were less
pronounced and not significant in children. There was an increase in the mortality hazard rate with each day?s delay in
initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard
ratio [HR 1?23] [95% CI 1?18?1?28]; p<0?0001 for the increasing HR with each day?s delay).
Interpretation
We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with
suspected or proven influenza infection.
full article
Comment