Muthuri, Stella G. and Venkatesan, Sudhir and Myles, Puja R. and Leonardi-Bee, Jo and Al Khuwaitir, Tarig S. and Al Mamun, Abdullah and Anovadiya, Ashish P. and Azziz-Baumgartner, Eduardo and Báez, Clarisa and Bassetti, Matteo and Beovic, Bojana and Bertisch, Barbara and Bonmarin, Isabelle and Booy, Robert and Borja-Aburto, Victor H. and Burgmann, Heinz and Cao, Bin and Carratala, Jordi and Denholm, Justin T. and Dominguez, Samuel R. and Duarte, Pericles A.D. and Dubnov-Raz, Gal and Echavarria, Marcela and Fanella, Sergio and Gao, Zhancheng and Gérardin, Patrick and Gianella, Maddalena and Gubbels, Sophie and Herberg, Jethro and Iglesias, Anjarath L. Higuera and Hoger, Peter H. and Hu, Xiaoyun and Islam, Quazi T. and Jiménez, Mirela F. and Kandeel, Amr and Keijzers, Gerben and Khalili, Hossein and Knight, Marian and Kudo, Koichiro and Kusznierz, Gabriela and Kuzman, Iljia and Kwan, Arthur M.C. and Amine, Idriss Lahlou and Langenegger, Eduard and Lankarani, Kamran B, and Leo, Yee-Sin and Linko, Rita and Liu, Pei and Madanat, Faris and Mayo-Montero, Elga and McGeer, Allison and Memish, Ziad and Metan, Gokhan and Mickiene, Aukse and Mikić, Dragan and Mohn, Kristin G. and Moradi, Ahmadreza and Nymadawa, Pagbajabyn and Oliva, Maria E. and Oskan, Mehpare and Parekh, Dhruv and Paul, Mical and Polack, Fernando P. and Rath, Barbara A. and Rodríguez, Alejandro H. and Sarrouf, Elena B. and Seale, Anna C. and Sertogullarindan, Bunyamin and Siqueira, Marilda M. and Skręt-Magierło, Joanna and Stephan, Frank and Talarek, Ewa and Tang, Julian W. and To, Kelvin K. and Torres, Antoni and Törün, Selda H. and Tran, Dat and Uyeki, Timothy M. and Van Zwol, Annelies and Vaudry, Wendy and Vidmar, Tjasa and Yokota, Renata T.C. and Zarogoulidis, Paul and Nguyen-Van-Tam, Jonathan
Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.
Lancet Respiratory Medicine, 2
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. 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. 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). We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection.
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