International audienceSummaryBackground 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. Funding F Hoffmann-La Roche

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Background. The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009–2010 pandemic has not been firmly established.Methods. We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models.Results. Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51–1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27–.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18–.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22–2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30–.56]).Conclusions. During the 2009–2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment.PROSPERO Registration. CRD42011001273.

BackgroundThe relationship between public transport use and acquisition of acute respiratory infection (ARI) is not well understood but potentially important during epidemics and pandemics.MethodsA case-control study performed during the 2008/09 influenza season. Cases (n = 72) consulted a General Practitioner with ARI, and controls with another non-respiratory acute condition (n = 66). Data were obtained on bus or tram usage in the five days preceding illness onset (cases) or the five days before consultation (controls) alongside demographic details. Multiple logistic regression modelling was used to investigate the association between bus or tram use and ARI, adjusting for potential confounders.ResultsRecent bus or tram use within five days of symptom onset was associated with an almost six-fold increased risk of consulting for ARI (adjusted OR = 5.94 95% CI 1.33-26.5). The risk of ARI appeared to be modified according to the degree of habitual bus and tram use, but this was not statistically significant (1-3 times/week: adjusted OR = 0.54 (95% CI 0.15-1.95; >3 times/week: 0.37 (95% CI 0.13-1.06).ConclusionsWe found a statistically significant association between ARI and bus or tram use in the five days before symptom onset. The risk appeared greatest among occasional bus or tram users, but this trend was not statistically significant. However, these data are plausible in relation to the greater likelihood of developing protective antibodies to common respiratory viruses if repeatedly exposed. The findings have differing implications for the control of seasonal acute respiratory infections and for pandemic influenza.