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

PRIDE Consortium Investigators; Stella G. Muthuri; Sudhir Venkatesan; Puja R. Myles; Jo Leonardi-Bee; Tarig S.A. Al Khuwaitir; Adbullah Al Mamun; Ashish P. Anovadiya; Eduardo Azziz-Baumgartner; Clarisa Báez; Matteo Bassetti; Bojana Beovic; Barbara Bertisch; Isabelle Bonmarin; Robert Booy; Victor H. Borja-Aburto; Heinz Burgmann; Bin Cao; Jordi Carratala; Justin T. Denholm; Samuel R. Dominguez; Pericles A.D. Duarte; Gal Dubnov-Raz; Marcela Echavarria; Sergio Fanella; Zhancheng Gao; Patrick Gérardin; Maddalena Giannella; Sophie Gubbels; Jethro Herberg; Anjarath L. Higuera Iglesias; Peter H. Hoger; Xiaoyun Hu; Quazi T. Islam; Mirela F. Jiménez; Amr Kandeel; Gerben Keijzers; Hossein Khalili; Marian Knight; Koichiro Kudo; Gabriela Kusznierz; Ilija Kuzman; Arthur M.C. Kwan; Idriss Lahlou Amine; Eduard Langenegger; Kamran B. Lankarani; Yee Sin Leo; Rita Linko; Pei Liu; Faris Madanat; Elga Mayo-Montero; Allison McGeer; Ziad Memish; Gokhan Metan; Aukse Mickiene; Dragan Mikic; Kristin G.I. Mohn; Ahmadreza Moradi; Pagbajabyn Nymadawa; Maria E. Oliva; Mehpare Ozkan; Dhruv Parekh; Mical Paul; Fernando P. Polack; Barbara A. Rath; Alejandro H. Rodríguez; Elena B. Sarrouf; Anna C. Seale; Bunyamin Sertogullarindan; Marilda M. Siqueira; Joanna Skret-Magierlo; Frank Stephan; Ewa Talarek; Julian W. Tang; Kelvin K.W. To; Antoni Torres; Selda H. Törün; Dat Tran; Timothy M. Uyeki; Annelies van Zwol; Wendy Vaudry; Tjasa Vidmar; Renata T.C. Yokota; Paul Zarogoulidis; Jonathan S. Nguyen-van-Tam

doi:10.1016/S2213-2600(14)70041-4

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

PRIDE Consortium Investigators, Stella G. Muthuri, Sudhir Venkatesan, Puja R. Myles, Jo Leonardi-Bee, Tarig S.A. Al Khuwaitir, Adbullah Al Mamun, Ashish P. Anovadiya, Eduardo Azziz-Baumgartner, Clarisa Báez, Matteo Bassetti, Bojana Beovic, Barbara Bertisch, Isabelle Bonmarin, Robert Booy, Victor H. Borja-Aburto, Heinz Burgmann, Bin Cao, Jordi Carratala, Justin T. DenholmSamuel R. Dominguez, Pericles A.D. Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L. Higuera Iglesias, Peter H. Hoger, Xiaoyun Hu, Quazi T. Islam, Mirela F. Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Marian Knight, Koichiro Kudo, Gabriela Kusznierz, Ilija Kuzman, Arthur M.C. Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B. Lankarani, Yee Sin Leo, Rita Linko, Pei Liu, Faris Madanat, Elga Mayo-Montero, Allison McGeer, Ziad Memish, Gokhan Metan, Aukse Mickiene, Dragan Mikic, Kristin G.I. Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Maria E. Oliva, Mehpare Ozkan, Dhruv Parekh, Mical Paul, Fernando P. Polack, Barbara A. Rath, Alejandro H. Rodríguez, Elena B. Sarrouf, Anna C. Seale, Bunyamin Sertogullarindan, Marilda M. Siqueira, Joanna Skret-Magierlo, Frank Stephan, Ewa Talarek, Julian W. Tang, Kelvin K.W. To, Antoni Torres, Selda H. Törün, Dat Tran, Timothy M. Uyeki, Annelies van Zwol, Wendy Vaudry, Tjasa Vidmar, Renata T.C. Yokota, Paul Zarogoulidis, Jonathan S. Nguyen-van-Tam^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

Background: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their eff ectiveness 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 signifi cant 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.

Original language	English
Pages (from-to)	395-404
Number of pages	10
Journal	The Lancet Respiratory Medicine
Volume	2
Issue number	5
DOIs	https://doi.org/10.1016/S2213-2600(14)70041-4
Publication status	Published - May 2014
Externally published	Yes

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10.1016/S2213-2600(14)70041-4

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant dataAccepted author manuscript, 784 KBLicence: CC BY-NC-ND

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PRIDE Consortium Investigators, Muthuri, S. G., Venkatesan, S., Myles, P. R., Leonardi-Bee, J., Al Khuwaitir, T. S. A., Al Mamun, A., Anovadiya, A. P., Azziz-Baumgartner, E., Báez, C., Bassetti, M., Beovic, B., Bertisch, B., Bonmarin, I., Booy, R., Borja-Aburto, V. H., Burgmann, H., Cao, B., Carratala, J., ... Nguyen-van-Tam, J. S. (2014). 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. The Lancet Respiratory Medicine, 2(5), 395-404. https://doi.org/10.1016/S2213-2600(14)70041-4

@article{a245963062d24280a64b3745c0e1152b,

title = "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",

abstract = "Background: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their eff ectiveness 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 signifi cant 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.",

author = "{PRIDE Consortium Investigators} and Muthuri, {Stella G.} and Sudhir Venkatesan and Myles, {Puja R.} and Jo Leonardi-Bee and {Al Khuwaitir}, {Tarig S.A.} and {Al Mamun}, Adbullah and Anovadiya, {Ashish P.} and Eduardo Azziz-Baumgartner and Clarisa B{\'a}ez and Matteo Bassetti and Bojana Beovic and Barbara Bertisch and Isabelle Bonmarin and Robert Booy and Borja-Aburto, {Victor H.} and Heinz Burgmann and Bin Cao and Jordi Carratala and Denholm, {Justin T.} and Dominguez, {Samuel R.} and Duarte, {Pericles A.D.} and Gal Dubnov-Raz and Marcela Echavarria and Sergio Fanella and Zhancheng Gao and Patrick G{\'e}rardin and Maddalena Giannella and Sophie Gubbels and Jethro Herberg and {Higuera Iglesias}, {Anjarath L.} and Hoger, {Peter H.} and Xiaoyun Hu and Islam, {Quazi T.} and Jim{\'e}nez, {Mirela F.} and Amr Kandeel and Gerben Keijzers and Hossein Khalili and Marian Knight and Koichiro Kudo and Gabriela Kusznierz and Ilija Kuzman and Kwan, {Arthur M.C.} and Amine, {Idriss Lahlou} and Eduard Langenegger and Lankarani, {Kamran B.} and Leo, {Yee Sin} and Rita Linko and Pei Liu and Faris Madanat and Elga Mayo-Montero and Allison McGeer and Ziad Memish and Gokhan Metan and Aukse Mickiene and Dragan Mikic and Mohn, {Kristin G.I.} and Ahmadreza Moradi and Pagbajabyn Nymadawa and Oliva, {Maria E.} and Mehpare Ozkan and Dhruv Parekh and Mical Paul and Polack, {Fernando P.} and Rath, {Barbara A.} and Rodr{\'i}guez, {Alejandro H.} and Sarrouf, {Elena B.} and Seale, {Anna C.} and Bunyamin Sertogullarindan and Siqueira, {Marilda M.} and Joanna Skret-Magierlo and Frank Stephan and Ewa Talarek and Tang, {Julian W.} and To, {Kelvin K.W.} and Antoni Torres and T{\"o}r{\"u}n, {Selda H.} and Dat Tran and Uyeki, {Timothy M.} and {van Zwol}, Annelies and Wendy Vaudry and Tjasa Vidmar and Yokota, {Renata T.C.} and Paul Zarogoulidis and Nguyen-van-Tam, {Jonathan S.} and Aguiar-Oliveira, {Maria de Lourdes} and {Al Masri}, Malakita and Robed Amin and Ara{\'u}jo, {Wildo N.} and Elena Ballester-Orcal and Carlos Bantar and Jing Bao and Barhoush, {Mazen M.} and Ariful Basher and Edgar Bautista and Julie Bettinger and Roland Bingisser and Emilio Bouza and Ilkay Bozkurt and Elvira Celjuska-To{\v s}ev and Chan, {Kenny K.C.} and Yusheng Chen and Tserendorj Chinbayar and Catia Cilloniz and Cox, {Rebecca J.} and Cuezzo, {Mar{\'i}a R.} and Wei Cui and Simin Dashti-Khavidaki and Bin du and {El Rhaffouli}, Hicham and Hernan Escobar and Agnieszka Florek-Michalska and James Fraser and John Gerrard and Stuart Gormley and Sandra G{\"o}tberg and Matthias Hoffmann and Behnam Honarvar and Jianmin Hu and Christoph Kemen and Gulam Khandaker and Koay, {Evelyn S.C.} and Miroslav Kojic and Kyaw, {Win M.} and Leonard Leibovici and Hongru Li and Li, {Xiao Li} and Romina Libster and Loh, {Tze P.} and Deborough Macbeth and Efstratios Maltezos and Toshie Manabe and Marcone, {D{\'e}bora N.} and Magdalena Marczynska and Mastalir, {Fabiane P.} and Mohsen Moghadami and Lilian Moriconi and Bulent Ozbay and Bla{\v z} Pe{\v c}avar and Wolfgang Poeppl and Poliquin, {Philippe G.} and Mahmudur Rahman and Alberto Rascon-Pacheco and Samir Refaey and Brunhilde Schweiger and Smith, {Fang G.} and Ayper Somer and Souza, {Thiago M.L.} and Payam Tabarsi and Tripathi, {Chandrabhanu B.} and Daiva Velyvyte and Diego Viasus and Qin Yu and Yuen, {Kwok Yung} and Wei Zhang and Wei Zuo",

year = "2014",

month = may,

doi = "10.1016/S2213-2600(14)70041-4",

language = "English",

volume = "2",

pages = "395--404",

journal = "The Lancet Respiratory Medicine",

issn = "2213-2600",

publisher = "Elsevier",

number = "5",

}

PRIDE Consortium Investigators, Muthuri, SG, Venkatesan, S, Myles, PR, Leonardi-Bee, J, Al Khuwaitir, TSA, Al Mamun, A, Anovadiya, AP, Azziz-Baumgartner, E, Báez, C, Bassetti, M, Beovic, B, Bertisch, B, Bonmarin, I, Booy, R, Borja-Aburto, VH, Burgmann, H, Cao, B, Carratala, J, Denholm, JT, Dominguez, SR, Duarte, PAD, Dubnov-Raz, G, Echavarria, M, Fanella, S, Gao, Z, Gérardin, P, Giannella, M, Gubbels, S, Herberg, J, Higuera Iglesias, AL, Hoger, PH, Hu, X, Islam, QT, Jiménez, MF, Kandeel, A, Keijzers, G, Khalili, H, Knight, M, Kudo, K, Kusznierz, G, Kuzman, I, Kwan, AMC, Amine, IL, Langenegger, E, Lankarani, KB, Leo, YS, Linko, R, Liu, P, Madanat, F, Mayo-Montero, E, McGeer, A, Memish, Z, Metan, G, Mickiene, A, Mikic, D, Mohn, KGI, Moradi, A, Nymadawa, P, Oliva, ME, Ozkan, M, Parekh, D, Paul, M, Polack, FP, Rath, BA, Rodríguez, AH, Sarrouf, EB, Seale, AC, Sertogullarindan, B, Siqueira, MM, Skret-Magierlo, J, Stephan, F, Talarek, E, Tang, JW, To, KKW, Torres, A, Törün, SH, Tran, D, Uyeki, TM, van Zwol, A, Vaudry, W, Vidmar, T, Yokota, RTC, Zarogoulidis, P & Nguyen-van-Tam, JS 2014, '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', The Lancet Respiratory Medicine, vol. 2, no. 5, pp. 395-404. https://doi.org/10.1016/S2213-2600(14)70041-4

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. / PRIDE Consortium Investigators; Muthuri, Stella G.; Venkatesan, Sudhir et al.
In: The Lancet Respiratory Medicine, Vol. 2, No. 5, 05.2014, p. 395-404.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - 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

AU - PRIDE Consortium Investigators

AU - Muthuri, Stella G.

AU - Venkatesan, Sudhir

AU - Myles, Puja R.

AU - Leonardi-Bee, Jo

AU - Al Khuwaitir, Tarig S.A.

AU - Al Mamun, Adbullah

AU - Anovadiya, Ashish P.

AU - Azziz-Baumgartner, Eduardo

AU - Báez, Clarisa

AU - Bassetti, Matteo

AU - Beovic, Bojana

AU - Bertisch, Barbara

AU - Bonmarin, Isabelle

AU - Booy, Robert

AU - Borja-Aburto, Victor H.

AU - Burgmann, Heinz

AU - Cao, Bin

AU - Carratala, Jordi

AU - Denholm, Justin T.

AU - Dominguez, Samuel R.

AU - Duarte, Pericles A.D.

AU - Dubnov-Raz, Gal

AU - Echavarria, Marcela

AU - Fanella, Sergio

AU - Gao, Zhancheng

AU - Gérardin, Patrick

AU - Giannella, Maddalena

AU - Gubbels, Sophie

AU - Herberg, Jethro

AU - Higuera Iglesias, Anjarath L.

AU - Hoger, Peter H.

AU - Hu, Xiaoyun

AU - Islam, Quazi T.

AU - Jiménez, Mirela F.

AU - Kandeel, Amr

AU - Keijzers, Gerben

AU - Khalili, Hossein

AU - Knight, Marian

AU - Kudo, Koichiro

AU - Kusznierz, Gabriela

AU - Kuzman, Ilija

AU - Kwan, Arthur M.C.

AU - Amine, Idriss Lahlou

AU - Langenegger, Eduard

AU - Lankarani, Kamran B.

AU - Leo, Yee Sin

AU - Linko, Rita

AU - Liu, Pei

AU - Madanat, Faris

AU - Mayo-Montero, Elga

AU - McGeer, Allison

AU - Memish, Ziad

AU - Metan, Gokhan

AU - Mickiene, Aukse

AU - Mikic, Dragan

AU - Mohn, Kristin G.I.

AU - Moradi, Ahmadreza

AU - Nymadawa, Pagbajabyn

AU - Oliva, Maria E.

AU - Ozkan, Mehpare

AU - Parekh, Dhruv

AU - Paul, Mical

AU - Polack, Fernando P.

AU - Rath, Barbara A.

AU - Rodríguez, Alejandro H.

AU - Sarrouf, Elena B.

AU - Seale, Anna C.

AU - Sertogullarindan, Bunyamin

AU - Siqueira, Marilda M.

AU - Skret-Magierlo, Joanna

AU - Stephan, Frank

AU - Talarek, Ewa

AU - Tang, Julian W.

AU - To, Kelvin K.W.

AU - Torres, Antoni

AU - Törün, Selda H.

AU - Tran, Dat

AU - Uyeki, Timothy M.

AU - van Zwol, Annelies

AU - Vaudry, Wendy

AU - Vidmar, Tjasa

AU - Yokota, Renata T.C.

AU - Zarogoulidis, Paul

AU - Nguyen-van-Tam, Jonathan S.

AU - Aguiar-Oliveira, Maria de Lourdes

AU - Al Masri, Malakita

AU - Amin, Robed

AU - Araújo, Wildo N.

AU - Ballester-Orcal, Elena

AU - Bantar, Carlos

AU - Bao, Jing

AU - Barhoush, Mazen M.

AU - Basher, Ariful

AU - Bautista, Edgar

AU - Bettinger, Julie

AU - Bingisser, Roland

AU - Bouza, Emilio

AU - Bozkurt, Ilkay

AU - Celjuska-Tošev, Elvira

AU - Chan, Kenny K.C.

AU - Chen, Yusheng

AU - Chinbayar, Tserendorj

AU - Cilloniz, Catia

AU - Cox, Rebecca J.

AU - Cuezzo, María R.

AU - Cui, Wei

AU - Dashti-Khavidaki, Simin

AU - du, Bin

AU - El Rhaffouli, Hicham

AU - Escobar, Hernan

AU - Florek-Michalska, Agnieszka

AU - Fraser, James

AU - Gerrard, John

AU - Gormley, Stuart

AU - Götberg, Sandra

AU - Hoffmann, Matthias

AU - Honarvar, Behnam

AU - Hu, Jianmin

AU - Kemen, Christoph

AU - Khandaker, Gulam

AU - Koay, Evelyn S.C.

AU - Kojic, Miroslav

AU - Kyaw, Win M.

AU - Leibovici, Leonard

AU - Li, Hongru

AU - Li, Xiao Li

AU - Libster, Romina

AU - Loh, Tze P.

AU - Macbeth, Deborough

AU - Maltezos, Efstratios

AU - Manabe, Toshie

AU - Marcone, Débora N.

AU - Marczynska, Magdalena

AU - Mastalir, Fabiane P.

AU - Moghadami, Mohsen

AU - Moriconi, Lilian

AU - Ozbay, Bulent

AU - Pečavar, Blaž

AU - Poeppl, Wolfgang

AU - Poliquin, Philippe G.

AU - Rahman, Mahmudur

AU - Rascon-Pacheco, Alberto

AU - Refaey, Samir

AU - Schweiger, Brunhilde

AU - Smith, Fang G.

AU - Somer, Ayper

AU - Souza, Thiago M.L.

AU - Tabarsi, Payam

AU - Tripathi, Chandrabhanu B.

AU - Velyvyte, Daiva

AU - Viasus, Diego

AU - Yu, Qin

AU - Yuen, Kwok Yung

AU - Zhang, Wei

AU - Zuo, Wei

PY - 2014/5

Y1 - 2014/5

N2 - Background: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their eff ectiveness 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 signifi cant 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.

AB - Background: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their eff ectiveness 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 signifi cant 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.

UR - http://www.scopus.com/inward/record.url?scp=84897142275&partnerID=8YFLogxK

U2 - 10.1016/S2213-2600(14)70041-4

DO - 10.1016/S2213-2600(14)70041-4

M3 - Article

C2 - 24815805

AN - SCOPUS:84897142275

SN - 2213-2600

VL - 2

SP - 395

EP - 404

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

IS - 5

ER -

PRIDE Consortium Investigators, Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TSA et al. 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. The Lancet Respiratory Medicine. 2014 May;2(5):395-404. doi: 10.1016/S2213-2600(14)70041-4

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

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