Dataset Information

Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data.

ABSTRACT:

Background

Observational studies claimed reducing effects of neuraminidase inhibitors (NI) on hospital mortality in patients with H1N1 influenza A. It has been criticized that such findings are prone to common and serious survival biases.

Methods

With observational data from the FLU-CIN study group, multi-state and dynamic prediction models have been used to avoid such biases. The data included 1391 patients with confirmed pandemic influenza A/H1N1 infection collected during 2009-2010 in the UK. Due to their close relationship, the main outcome measures were hospital death and length of hospital stay.

Findings

There is no direct effect of NI on the hospital death rate; the hazard ratio (HR) of NI was 1.03 (95%-CI: 0.64-1.66). The discharge rate is increased for NI patients (HR = 1.89 (95%-CI: 1.65-2.16)) indicating that NI-treated patients stay shorter in hospital than NI-untreated patients, on average 3.10 days (95%-CI: 2.07-4.14). We also showed that the initiation timing of NI treatment (? 2 days versus > 2 days after onset) made no difference on the effects on the hospital death and discharge hazards. The hazard ratios remain stable after adjusting for potential confounders measured at admission (such as comorbidities and influenza-related clinical symptoms).

Conclusions

The potential beneficial effect of NI on hospitalized patients in the UK is rather a reduction of the length of hospital stay than a reduction of the mortality rate. There seems to be no confounding by indication and no differences if NI is given early or late. Different effects could be present in other populations (such as non-hospitalized individuals) or countries. Careful interpretation of the effect on length of hospital stay is needed due to potentially different discharge policies of NI-treated and NI-untreated patients.

SUBMITTER: Wolkewitz M

PROVIDER: S-EPMC5008789 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data.

Wolkewitz Martin M Schumacher Martin M

PloS one 20160901 9

<h4>Background</h4>Observational studies claimed reducing effects of neuraminidase inhibitors (NI) on hospital mortality in patients with H1N1 influenza A. It has been criticized that such findings are prone to common and serious survival biases.<h4>Methods</h4>With observational data from the FLU-CIN study group, multi-state and dynamic prediction models have been used to avoid such biases. The data included 1391 patients with confirmed pandemic influenza A/H1N1 infection collected during 2009- ...[more]

PMID: 27583403

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Project description:BackgroundNeuraminidase 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.MethodsWe 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.FindingsWe 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).InterpretationWe advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.FundingF Hoffmann-La Roche.

Dataset Information

Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data.

Background

Methods

Findings

Conclusions

Publications

Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data.

Similar Datasets

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