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1. Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

Author

Venkatesan S, Myles PR, Bolton KJ, Muthuri SG, Al Khuwaitir T, Anovadiya AP, Azziz-Baumgartner E, Bajjou T, Bassetti M, Beovic B, Bertisch B, Bonmarin I, Booy R, Borja-Aburto VH, Burgmann H, Cao B, Carratala J, Chinbayar T, Cilloniz C, Denholm JT, Dominguez SR, Duarte PAD, Dubnov-Raz G, Fanella S, Gao Z, Gérardin P, Giannella M, Gubbels S, Herberg J, Higuera Iglesias AL, Hoeger PH, Hu XY, Islam QT, Jiménez MF, Keijzers G, Khalili H, Kusznierz G, Kuzman I, Langenegger E, Lankarani KB, Leo YS, Libster RP, Linko R, Madanat F, Maltezos E, Mamun A, Manabe T, Metan G, Mickiene A, Mikić D, Mohn KGI, Oliva ME, Ozkan M, Parekh D, Paul M, Rath BA, Refaey S, Rodríguez AH, Sertogullarindan B, Skręt-Magierło J, Somer A, Talarek E, Tang JW, To K, Tran D, Uyeki TM, Vaudry W, Vidmar T, Zarogoulidis P, and Nguyen-Van-Tam JS

Subjects
Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Aged, Anti-Bacterial Agents therapeutic use, Child, Enzyme Inhibitors pharmacology, Female, Humans, Male, Middle Aged, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Enzyme Inhibitors therapeutic use, Influenza A Virus, H1N1 Subtype, Influenza, Human drug therapy, Influenza, Human epidemiology, Length of Stay, Neuraminidase antagonists & inhibitors, Pandemics
Abstract

Background: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear., Methods: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded., Results: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS., Conclusions: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Published
2020
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2. Impact of Outpatient Neuraminidase Inhibitor Treatment in Patients Infected With Influenza A(H1N1)pdm09 at High Risk of Hospitalization: An Individual Participant Data Metaanalysis.

Author

Venkatesan S, Myles PR, Leonardi-Bee J, Muthuri SG, Al Masri M, Andrews N, Bantar C, Dubnov-Raz G, Gérardin P, Koay ESC, Loh TP, Memish Z, Miller E, Oliva ME, Rath BA, Schweiger B, Tang JW, Tran D, Vidmar T, Waight PA, and Nguyen-Van-Tam JS

Subjects
Adolescent, Adult, Aged, Ambulatory Care, Anti-Bacterial Agents therapeutic use, Antiviral Agents administration & dosage, Enzyme Inhibitors administration & dosage, Female, Hospitalization, Humans, Influenza, Human diagnosis, Influenza, Human virology, Male, Middle Aged, Odds Ratio, Outpatients, Regression Analysis, Risk Factors, Young Adult, Antiviral Agents therapeutic use, Enzyme Inhibitors therapeutic use, Influenza A Virus, H1N1 Subtype drug effects, Influenza, Human drug therapy, Neuraminidase antagonists & inhibitors
Abstract

Background: While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established. We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection., Methods: We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010. We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization. We adjusted for NAI treatment propensity and preadmission antibiotic use, including "study center" as a random intercept to account for differences in baseline hospitalization rate between centers., Results: We included 3376 patients with influenza A(H1N1)pdm09, of whom 3085 (91.4%) had laboratory-confirmed infection. Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%). After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20-0.30)., Conclusions: In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission. These data suggest that community patients with severe influenza should receive NAI treatment., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Published
2017
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3. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

Author

Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Lim WS, Al Mamun A, Anovadiya AP, Araújo WN, Azziz-Baumgartner E, Báez C, Bantar C, Barhoush MM, Bassetti M, Beovic B, Bingisser R, Bonmarin I, Borja-Aburto VH, Cao B, Carratala J, Cuezzo MR, Denholm JT, Dominguez SR, Duarte PA, Dubnov-Raz G, Echavarria M, Fanella S, Fraser J, Gao Z, Gérardin P, Giannella M, Gubbels S, Herberg J, Higuera Iglesias AL, Hoeger PH, Hoffmann M, Hu X, Islam QT, Jiménez MF, Kandeel A, Keijzers G, Khalili H, Khandaker G, Knight M, Kusznierz G, Kuzman I, Kwan AM, Lahlou Amine I, Langenegger E, Lankarani KB, Leo YS, Linko R, Liu P, Madanat F, Manabe T, Mayo-Montero E, McGeer A, Memish ZA, Metan G, Mikić D, Mohn KG, Moradi A, Nymadawa P, Ozbay B, Ozkan M, Parekh D, Paul M, Poeppl W, Polack FP, Rath BA, Rodríguez AH, Siqueira MM, Skręt-Magierło J, Talarek E, Tang JW, Torres A, Törün SH, Tran D, Uyeki TM, van Zwol A, Vaudry W, Velyvyte D, Vidmar T, Zarogoulidis P, and Nguyen-Van-Tam JS

Subjects
Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Anti-Bacterial Agents therapeutic use, Child, Child, Preschool, Enzyme Inhibitors therapeutic use, Female, Humans, Influenza, Human epidemiology, Influenza, Human mortality, Influenza, Human virology, Male, Middle Aged, Odds Ratio, Pneumonia, Viral diagnostic imaging, Pneumonia, Viral epidemiology, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Influenza A Virus, H1N1 Subtype drug effects, Influenza A Virus, H1N1 Subtype enzymology, Influenza, Human drug therapy, Neuraminidase antagonists & inhibitors, Pneumonia, Viral drug therapy, Pneumonia, Viral virology
Abstract

Background: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection., Methods: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids., Results: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]., Conclusions: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support., (© 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Published
2016
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4. Statistical and methodological concerns about the beneficial effect of neuraminidase inhibitors on mortality.

Author

Leonardi-Bee J, Venkatesan S, Muthuri SG, Nguyen-Van-Tam JS, and Myles PR

Subjects
Female, Humans, Male, Antiviral Agents therapeutic use, Enzyme Inhibitors therapeutic use, Influenza A Virus, H1N1 Subtype, Influenza, Human drug therapy, Neuraminidase antagonists & inhibitors, Oseltamivir therapeutic use, Pandemics, Zanamivir therapeutic use
Published
2014
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5. 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.

Author

Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, 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 PA, Dubnov-Raz G, Echavarria M, Fanella S, Gao Z, Gérardin P, Giannella M, Gubbels S, Herberg J, 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 AM, 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, Mikić D, Mohn KG, 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, Skręt-Magierło J, Stephan F, Talarek E, Tang JW, To KK, Torres A, Törün SH, Tran D, Uyeki TM, Van Zwol A, Vaudry W, Vidmar T, Yokota RT, Zarogoulidis P, and Nguyen-Van-Tam JS

Subjects
Adolescent, Adult, Child, Female, Hospitalization, Humans, Influenza, Human mortality, Male, Middle Aged, Proportional Hazards Models, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Enzyme Inhibitors therapeutic use, Influenza A Virus, H1N1 Subtype, Influenza, Human drug therapy, Neuraminidase antagonists & inhibitors, Oseltamivir therapeutic use, Pandemics, Zanamivir therapeutic use
Abstract

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., Funding: F Hoffmann-La Roche., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
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8. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-2010 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients.

Author

Muthuri SG, Myles PR, Venkatesan S, Leonardi-Bee J, and Nguyen-Van-Tam JS

Subjects
Humans, Influenza, Human drug therapy, Influenza, Human virology, Public Health, Time Factors, Treatment Outcome, Antiviral Agents therapeutic use, Enzyme Inhibitors therapeutic use, Influenza A Virus, H1N1 Subtype drug effects, Influenza, Human complications, Influenza, Human mortality, Neuraminidase antagonists & inhibitors, Pandemics
Abstract

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.

Published
2013
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9. Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

Author

Venkatesan, Sudhir, Myles, Puja R, Bolton, Kirsty J, Muthuri, Stella G, Al Khuwaitir, Tarig, Anovadiya, Ashish P, Azziz-Baumgartner, Eduardo, Bajjou, Tahar, Bassetti, Matteo, Beovic, Bojana, Bertisch, Barbara, Bonmarin, Isabelle, Booy, Robert, Borja-Aburto, Victor H, Burgmann, Heinz, Cao, Bin, Carratala, Jordi, Chinbayar, Tserendorj, Cilloniz, Catia, Denholm, Justin T, Dominguez, Samuel R, Duarte, Pericles A D, Dubnov-Raz, Gal, Fanella, Sergio, Gao, Zhancheng, Gérardin, Patrick, Giannella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Higuera Iglesias, Anjarath Lorena, Hoeger, Peter H, Hu, Xiao Yun, Islam, Quazi T, Jiménez, Mirela F, Keijzers, Gerben, Khalili, Hossein, Kusznierz, Gabriela, Kuzman, Ilija, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Libster, Romina P, Linko, Rita, Madanat, Faris, Maltezos, Efstratios, Mamun, Abdullah, Manabe, Toshie, Metan, Gokhan, Mickiene, Auksė, Mikić, Dragan, Mohn, Kristin G I, Oliva, Maria E, Ozkan, Mehpare, Parekh, Dhruv, Paul, Mical, Rath, Barbara A, Refaey, Samir, Rodríguez, Alejandro H, Sertogullarindan, Bunyamin, Skręt-Magierło, Joanna, Somer, Ayper, Talarek, Ewa, Tang, Julian W, To, Kelvin, Tran, Dat, Uyeki, Timothy M, Vaudry, Wendy, Vidmar, Tjasa, Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan S, PRIDE Consortium Investigators, Imperial College London, HUS Perioperative, Intensive Care and Pain Medicine, Department of Diagnostics and Therapeutics, Clinicum, Venkatesan S., Myles P.R., Bolton K.J., Muthuri S.G., Al Khuwaitir T., Anovadiya A.P., Azziz-Baumgartner E., Bajjou T., Bassetti M., Beovic B., Bertisch B., Bonmarin I., Booy R., Borja-Aburto V.H., Burgmann H., Cao B., Carratala J., Chinbayar T., Cilloniz C., Denholm J.T., Dominguez S.R., Duarte P.A.D., Dubnov-Raz G., Fanella S., Gao Z., Gerardin P., Giannella M., Gubbels S., Herberg J., Higuera Iglesias A.L., Hoeger P.H., Hu X.Y., Islam Q.T., Jimenez M.F., Keijzers G., Khalili H., Kusznierz G., Kuzman I., Langenegger E., Lankarani K.B., Leo Y.-S., Libster R.P., Linko R., Madanat F., Maltezos E., Mamun A., Manabe T., Metan G., Mickiene A., Mikic D., Mohn K.G.I., Oliva M.E., Ozkan M., Parekh D., Paul M., Rath B.A., Refaey S., Rodriguez A.H., Sertogullarindan B., Skret-Magierlo J., Somer A., Talarek E., Tang J.W., To K., Tran D., Uyeki T.M., Vaudry W., Vidmar T., Zarogoulidis P., and Nguyen-Van-Tam J.S.

Subjects
0301 basic medicine, Male, pandemic influenza, OSELTAMIVIR TREATMENT, IMPACT, Neuraminidase/antagonists & inhibitors, CHILDREN, medicine.disease_cause, 0302 clinical medicine, antivirals, Influenza A Virus, H1N1 Subtype, Adrenal Cortex Hormones, IPD meta-analysi, Influenza A virus, Immunology and Allergy, 030212 general & internal medicine, IPD meta-analysis, Young adult, Enzyme Inhibitors, Child, 11 Medical and Health Sciences, RISK, 11832 Microbiology and virology, Antiviral Agents/therapeutic use, OUTCOMES, COMPLICATIONS, biology, Neuraminidase inhibitor, Enzyme inhibitors, Middle Aged, Antivirals, antiviral, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Treatment Outcome, Meta-analysis, Cohort, Viruses, Enzyme Inhibitors/pharmacology/therapeutic use, Female, Pandemic influenza, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, 030106 microbiology, IPD meta-analysis, Neuraminidase inhibitors, antivirals, length of stay, pandemic influenza, Neuraminidase, Adrenal Cortex Hormones/therapeutic use, Microbiology, Antiviral Agents, PRIDE Consortium Investigators, Grip, 03 medical and health sciences, Major Articles and Brief Reports, Young Adult, Pharmacotherapy, Internal medicine, Influenza, Human, medicine, Humans, COHORT, Pandemics, ddc:613, Aged, Neuraminidase inhibitors, business.industry, CLINICAL-FEATURES, ADULTS, 06 Biological Sciences, Influenza, Human/drug therapy/epidemiology, Length of Stay, Confidence interval, Influenza, Editor's Choice, Anti-Bacterial Agents/therapeutic use, Inhibidors enzimàtics, 3121 General medicine, internal medicine and other clinical medicine, biology.protein, business, RESISTANCE
Abstract

Background The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. Methods We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of, We found that neuraminidase inhibitor (NAI) treatment initiated on hospital admission to patients with clinically diagnosed or laboratory-confirmed A(H1N1)pdm09 virus infection was associated with a reduction in hospital length of stay when compared to later or no NAI treatment.

Published
2018

10. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis

Author

Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi Bee, Jo, Lim, Wei Shen, Al Mamun, Abdullah, Anovadiya, Ashish P., Araújo, Wildo N., Azziz Baumgartner, Eduardo, Báez, Clarisa, Bantar, Carlos, Barhoush, Mazen M., Bassetti, Matteo, Beovic, Bojana, Bingisser, Roland, Bonmarin, Isabelle, Borja Aburto, Victor H., Cao, Bin, Carratala, Jordi, Cuezzo, María R., Denholm, Justin T., Dominguez, Samuel R., Duarte, Pericles A. D., Dubnov Raz, Gal, Echavarria, Marcela, Fanella, Sergio, Fraser, James, Gao, Zhancheng, Gérardin, Patrick, Giannella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Higuera Iglesias, Anjarath L., Hoeger, Peter H., Hoffmann, Matthias, Xiaoyun, Hu, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Khandaker, Gulam, Knight, Marian, Kusznierz, Gabriela, Kuzman, Ilija, Kwan, Arthur M. C., Lahlou Amine, Idriss, Langenegger, Eduard, Lankarani, Kamran B., Leo, Yee Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Manabe, Toshie, Mayo Montero, Elga, Mcgeer, Allison, Memish, Ziad A., Metan, Gokhan, Mikić, Dragan, Mohn, Kristin G. I., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Ozbay, Bulent, Ozkan, Mehpare, Parekh, Dhruv, Paul, Mical, Poeppl, Wolfgang, Polack, Fernando P., Rath, Barbara A., Rodríguez, Alejandro H., Siqueira, Marilda M., Skrȩt Magierło, Joanna, Talarek, Ewa, Tang, Julian W., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., van Zwol, Annelies, Vaudry, Wendy, Velyvyte, Daiva, Vidmar, Tjasa, Zarogoulidis, Paul, Nguyen Van Tam, Jonathan S, de Lourdes Aguiar Oliveira, Maria, Al Khuwaitir, Tarig S. A., Al Masri, Malakita, Amin, Robed, Ballester Orcal, Elena, Bao, Jing, Basher, Ariful, Bautista, Edgar, Bertisch, Barbara, Bettinger, Julie, Booy, Robert, Bouza, Emilio, Bozkurt, Ilkay, Burgmann, Heinz, Čeljuska Tošev, Elvira, Chan, Kenny K. C., Chen, Yusheng, Chinbayar, Tserendorj, Cilloniz, Catia, Cox, Rebecca J., Sarrouf, Elena B., Cui, Wei, Dashti Khavidaki, Simin, Bin, Du, El Rhaffouli, Hicham, Escobar, Hernan, Florek Michalska, Agnieszka, Gerrard, John, Gormley, Stuart, Götberg, Sandra, Honarvar, Behnam, Jianming, Hu, Kemen, Christoph, Koay, Evelyn S. C., Kojic, Miroslav, Kudo, Koichiro, Kyaw, Win M., Leibovici, Leonard, Xiao li, Li, Hongru, Li, Libster, Romina, Loh, Tze P., Macbeth, Deborough, Maltezos, Efstratios, Marcone, Debora N., Marczynska, Magdalena, Mastalir, Fabiane P., Mickiene, Aukse, Moghadami, Mohsen, Moriconi, Lilian, Oliva, Maria E., Pečavar, Blaž, Poliquin, Philippe G., Rahman, Mahmudur, Rascon Pacheco, Alberto, Refaey, Samir, Schweiger, Brunhilde, Seale, Anna C., Sertogullarindan, Bunyamin, Smith, Fang G., Somer, Ayper, Souza, Thiago M. L., Stephan, Frank, Tabarsi, Payam, Tripathi, C. B., Viasus, Diego, Qin, Yu, Zhang, Wei, Zuo, Wei, Universitat de Barcelona, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Institut de Veille Sanitaire (INVS), Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Diseases, Department of physics, engineering physics and astronomy, Queen's University [Kingston, Canada], Peking University People's Hospital, Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), National Perinatal Epidemiology Unit, University of Oxford [Oxford], Instituto Nacional de Enfermedades Respiratorias Dr. Emilio Coni [Santa Fe, Argentina] (INER), State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology [Wuhan] (HUST), People's Hospital of Peking University (PKUPH), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi Bee, Jo, Lim, Wei Shen, Al Mamun, Abdullah, Anovadiya, Ashish P., Araújo, Wildo N., Azziz Baumgartner, Eduardo, Báez, Clarisa, Bantar, Carlo, Barhoush, Mazen M., Bassetti, Matteo, Beovic, Bojana, Bingisser, Roland, Bonmarin, Isabelle, Borja Aburto, Victor H., Cao, Bin, Carratala, Jordi, Cuezzo, María R., Denholm, Justin T., Dominguez, Samuel R., Duarte, Pericles A. D., Dubnov Raz, Gal, Echavarria, Marcela, Fanella, Sergio, Fraser, Jame, Gao, Zhancheng, Gérardin, Patrick, Giannella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Higuera Iglesias, Anjarath L., Hoeger, Peter H., Hoffmann, Matthia, Xiaoyun, Hu, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Khandaker, Gulam, Knight, Marian, Kusznierz, Gabriela, Kuzman, Ilija, Kwan, Arthur M. C., Lahlou Amine, Idri, Langenegger, Eduard, Lankarani, Kamran B., Leo, Yee Sin, Linko, Rita, Liu, Pei, Madanat, Fari, Manabe, Toshie, Mayo Montero, Elga, Mcgeer, Allison, Memish, Ziad A., Metan, Gokhan, Mikić, Dragan, Mohn, Kristin G. I., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Ozbay, Bulent, Ozkan, Mehpare, Parekh, Dhruv, Paul, Mical, Poeppl, Wolfgang, Polack, Fernando P., Rath, Barbara A., Rodríguez, Alejandro H., Siqueira, Marilda M., Skrȩt Magierło, Joanna, Talarek, Ewa, Tang, Julian W., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., van Zwol, Annelie, Vaudry, Wendy, Velyvyte, Daiva, Vidmar, Tjasa, Zarogoulidis, Paul, Nguyen Van Tam, Jonathan S, de Lourdes Aguiar Oliveira, Maria, Al Khuwaitir, Tarig S. A., Al Masri, Malakita, Amin, Robed, Ballester Orcal, Elena, Bao, Jing, Basher, Ariful, Bautista, Edgar, Bertisch, Barbara, Bettinger, Julie, Booy, Robert, Bouza, Emilio, Bozkurt, Ilkay, Burgmann, Heinz, Čeljuska Tošev, Elvira, Chan, Kenny K. C., Chen, Yusheng, Chinbayar, Tserendorj, Cilloniz, Catia, Cox, Rebecca J., Sarrouf, Elena B., Cui, Wei, Dashti Khavidaki, Simin, Bin, Du, El Rhaffouli, Hicham, Escobar, Hernan, Florek Michalska, Agnieszka, Gerrard, John, Gormley, Stuart, Götberg, Sandra, Honarvar, Behnam, Jianming, Hu, Kemen, Christoph, Koay, Evelyn S. C., Kojic, Miroslav, Kudo, Koichiro, Kyaw, Win M., Leibovici, Leonard, Xiao li, Li, Hongru, Li, Libster, Romina, Loh, Tze P., Macbeth, Deborough, Maltezos, Efstratio, Marcone, Debora N., Marczynska, Magdalena, Mastalir, Fabiane P., Mickiene, Aukse, Moghadami, Mohsen, Moriconi, Lilian, Oliva, Maria E., Pečavar, Blaž, Poliquin, Philippe G., Rahman, Mahmudur, Rascon Pacheco, Alberto, Refaey, Samir, Schweiger, Brunhilde, Seale, Anna C., Sertogullarindan, Bunyamin, Smith, Fang G., Somer, Ayper, Souza, Thiago M. L., Stephan, Frank, Tabarsi, Payam, Tripathi, C. B., Viasus, Diego, Qin, Yu, Zhang, Wei, Zuo, Wei, Pediatric surgery, and ICaR - Circulation and metabolism

Subjects
Hospitalisation, Individual participant data meta-analyses, Influenza-related pneumonia, Neuraminidase inhibitors, Adolescent, Adrenal Cortex Hormones, Adult, Anti-Bacterial Agents, Antiviral Agents, Child, Child, Preschool, Enzyme Inhibitors, Female, Humans, Influenza, Human, Male, Middle Aged, Neuraminidase, Odds Ratio, Pneumonia, Viral, Treatment Outcome, Young Adult, Influenza A Virus, H1N1 Subtype, 0301 basic medicine, Epidemiology, [SDV]Life Sciences [q-bio], viruses, Meta-análises de dados de participantes individuais, Antibiotics, Pneumònia, Adrenal Cortex Hormone, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, influenza-related pneumonia, neuraminidase inhibitors, 0302 clinical medicine, individual participant data meta‐analyses, Influenza A Virus, Enzyme Inhibitor, 030212 general & internal medicine, Viral, Incidence (epidemiology), Inibidores da neuraminidase, virus diseases, 3. Good health, Hospitalization, Infectious Diseases, Meta-analysis, Original Article, Individual participant data meta-analyse, Public Health, Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Antagonists & inhibitors, medicine.drug_class, influenza-related pneumonia, 030106 microbiology, influenza‐related pneumonia, Neuraminidase inhibitor, Ingressos i altes en els hospitals, Public Health, Environmental and Occupational Health, 03 medical and health sciences, Open Access, Pneumonia relacionada à gripe, Pharmacotherapy, Internal medicine, Anti-Bacterial Agent, medicine, H1N1 Subtype, Preschool, Antiviral Agent, Hospitalização, Hospital admission and discharge, business.industry, Environmental and Occupational Health, individual participant data meta-analyses, Original Articles, Odds ratio, Pneumonia, medicine.disease, Influenza, respiratory tract diseases, El Niño, Immunology, business
Abstract

Stella G. Muthuri,1 Sudhir Venkatesan,1 Puja R. Myles,1 Jo Leonardi-Bee,1 Wei Shen Lim,2 Abdullah Al Mamun,3 Ashish P. Anovadiya,4 Wildo N. Ara ujo,5 Eduardo Azziz-Baumgartner,6 Clarisa B aez,7 Carlos Bantar,8 Mazen M. Barhoush,9 Matteo Bassetti,10 Bojana Beovic,11 Roland Bingisser,12 Isabelle Bonmarin,13 Victor H. Borja-Aburto,14 Bin Cao,15 Jordi Carratala,16 Mar ıa R. Cuezzo,17 Justin T. Denholm,18 Samuel R. Dominguez,19 Pericles A. D. Duarte,20 Gal Dubnov-Raz,21 Marcela Echavarria,22 Sergio Fanella,23 James Fraser,24 Zhancheng Gao,25 Patrick G erardin,26,27,28,29 Maddalena Giannella,30 Sophie Gubbels,31 Jethro Herberg,32 Anjarath L. Higuera Iglesias,33 Peter H. Hoeger,34 Matthias Hoffmann,35 Xiaoyun Hu,36 Quazi T. Islam,37 Mirela F. Jim enez,38 Amr Kandeel,39 Gerben Keijzers,40 Hossein Khalili,41 Gulam Khandaker,42 Marian Knight,43 Gabriela Kusznierz,44 Ilija Kuzman,45 Arthur M. C. Kwan,46 Idriss Lahlou Amine,47 Eduard Langenegger,48 Kamran B. Lankarani,49 Yee-Sin Leo,50 Rita Linko,51 Pei Liu,52 Faris Madanat,53 Toshie Manabe,54 Elga Mayo-Montero,55 Allison McGeer,56 Ziad A. Memish,57,58 Gokhan Metan,59 Dragan Miki c,60 Kristin G. I. Mohn,61,62 Ahmadreza Moradi,63,64 Pagbajabyn Nymadawa,65 Bulent Ozbay,66 Mehpare Ozkan,67 Dhruv Parekh,68 Mical Paul,69 Wolfgang Poeppl,70 Fernando P. Polack,71,72 Barbara A. Rath,73 Alejandro H. Rodr ıguez,74 Marilda M. Siqueira,75 Joanna Skre zt-Magierło,76 Ewa Talarek,77 Julian W. Tang,78,79,80 Antoni Torres,81 Selda H. T€ or€un,82 Dat Tran,83 Timothy M. Uyeki,84 Annelies van Zwol,85 Wendy Vaudry,86 Daiva Velyvyte,87 Tjasa Vidmar,88 Paul Zarogoulidis,89 PRIDE Consortium Investigators* Jonathan S. Nguyen-Van-Tam1 1Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK. 2Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK. 3International Centre for Diarrhoeal Diseases, Research Bangladesh (ICDDRB), Dhaka, Bangladesh. 4Department of Pharmacology, Government Medical College and Sir Takhtsinhji General Hospital, Bhavnagar, Gujarat, India. 5University of Bras ılia, Bras ılia, DF, Brazil. 6Centers for Disease Control and Prevention, Atlanta, GA, USA. 7Ministerio de Salud de la Provincia de Buenos Aires, Buenos Aires, Argentina. 8Department of Infection Control, Hospital San Mart ın de Paran a, Entre R ıos, Argentina. 9Department of Medicine, King Saud Medical City, Riyadh, Saudi Arabia. 10Santa Maria Misericordia Hospital, Udine, Italy. 11Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia. 12Department of Emergency Medicine, University Hospital Basel, Basel, Switzerland. 13Institut de Veille Sanitaire, Saint-Maurice, France. 14Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico. 15Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. 16Department of Infectious Diseases, Hospital Universitari de Bellvitge, Bellvitge Institute for Biomedical Research, L’Hospitalet de Llobregat, Red Espa~nola de Investigaci on en Patolog ıa Infecciosa, University of Barcelona, Barcelona, Spain. 17Ministerio de Salud de Tucum an, Tucum an, Argentina. 18Victorian Infectious Diseases Service and Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Parkville, Vic., Australia. 19Department of Pediatric Infectious Diseases, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA. 20Universidade Estadual do Oeste do Parana ´, UNIOESTE, Cascavel, PR, Brazil. 21The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Israel. 22Clinical Virology Laboratory, CEMIC University Hospital, Buenos Aires, Argentina. 23Section of Pediatric Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada. 24Paediatric Intensive Care Unit, Bristol Children’s Hospital, Bristol, UK. 25Department of Respiratory & Critical Care Medicine, Peking University People’s Hospital, Beijing, China. 26NICU/PICU, PFME, CHU Saint Pierre, Saint Pierre, La R eunion, France. 27CIC 1410 (CHU/Inserm/University of La Re ´union/URML-OI), CHU Saint Pierre, Saint Pierre, La Réunion, France. 28UMR PIMIT (CHU/Inserm/University of La Re ´union/IRD/CNRS), CYROI, Saint Denis – Reunion Island, Saint Denis, France. 29NICU/PICU CHU of La Re ´union, Groupe Hospitalier Sud Re ´union, Saint Pierre, La Re ´union, France. 30Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Maran ˜o ´n, Madrid, Spain. 31Department of Infectious Disease Epidemiology, Sector for National Health Documentation and Research, Statens Serum Institut, Copenhagen, Denmark. 32Section of Paediatrics, Division of Infectious Disease, Imperial College, London, UK. 33Epidemiology Research Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosı ´o Villegas, Mexico City, Mexico. 34Cath. Children’s Hospital Wilhelmstift, Hamburg, Germany. 35Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 36Peking Union Medical College Hospital, Beijing, China. 37Dhaka Medical College Hospital, Dhaka, Bangladesh. 38Departamento de Ginecologia e Obstetrı ´cia – UFCSPA, Preceptora da Reside ˆncia Me ´dica do Hospital Fe ˆmina, Porto Alegre, Brazil. 39Ministry of Health in Egypt, Cairo, Egypt. 40Gold Coast Hospital, Gold Coast, Qld, Australia. 41Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 42National Centre for Immunisation Research and Surveillance (NCIRS), The Children’s Hospital at Westmead, University of Sydney, Sydney, NSW, Australia. 43National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 44National Institute of Respiratory Diseases ‘Emilio Coni’ ANLIS “C. Malbran”, Santa Fe, Argentina. 45School of Medicine, University Hospital for Infectious Diseases, University of Zagreb, Zagreb, Croatia. 46Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong. 47Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Biosafety Level 3 and Research Laboratory, University Mohammed V-Souissi, Rabat, Morocco. 48Department of Obstetrics and Gynaecology, Stellenbosch University and Tygerberg, Stellenbosch, South Africa. 49Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 50Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore. 51Helsinki University Hospital, Helsinki, Finland. 52Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang, China. 53Department of Pediatrics, King Hussein Cancer Center, Amman, Jordan. 54Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan. 55Instituto de Medicina Preventiva de la Defensa, Capitan Medico Ramon y Cajal (IMPDEF), Ministerio de Defensa, Madrid, Spain. 56Toronto Invasive Bacterial Diseases Network, University of Toronto, Toronto, ON, Canada. 57Ministry of Health, Riyadh, Saudi Arabia. 58College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. 59Department of Infectious Diseases and Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri, Turkey. 60Military Medical Academy, Clinic for Infectious and Tropical Diseases, Belgrade, Serbia. 61Section for Infectious Diseases, Medical Department, and Department of Research and Development, Haukeland University Hospital, Bergen, Norway. 62Department of Clinical Science, The Influenza Centre, University of Bergen, Bergen, Norway. 63The Division of Ocular Immunology, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 64National Research Institute for Tuberculosis and Lung Disease, Massih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 65National Influenza Center, National Center of Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia. 66Department of Pulmonary and Critical Care, Yuzuncu Yil University Medical Faculty, Van, Turkey. 67Clinic of Pediatric Neurology, Dr. Sami Ulus Research and Training Hospital of Women’s and Children’s Health and Diseases, Ankara, Turkey. 68Critical Care and Pain Perioperative, Critical Care and Trauma Trials Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. 69Division of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel. 70Medical University of Vienna, Vienna, Austria. 71Department of Pediatrics, Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA. 72Fundacion INFANT, Buenos Aires, Argentina. 73Division of Pneumonology-Immunology, Department of Pediatrics, Charite ´ University Medical Center, Berlin, Germany. 74Critical Care Department, Hospital Joan XXIII, IISPV, URV, CIBERES, Tarragona, Spain. 75Laboratory of Respiratory Viruses, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Brazil. 76Uniwersytet Rzeszowski, Rzeszo ´w, Poland. 77Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland. 78Division of Microbiology/Molecular Diagnostic Centre, Department of Laboratory Medicine, National University Hospital, Singapore, Singapore. 79Alberta Provincial Laboratory for Public Health, University of Alberta Hospital, Edmonton, Canada. 80Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada. 81Hospital Clinic, University of Barcelona, IDIBAPS, CIBERES, Barcelona, Spain. 82Department of Pediatric Infectious Diseases, Istanbul Medical Faculty, Istanbul, Turkey. 83Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Canada. 84Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. 85Department of Pediatric Intensive Care, VU University Medical Center, Amsterdam, The Netherlands. 86Division of Infectious Diseases, Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada. 87Lithuanian University of Health Sciences, Kaunas, Lithuania. 88General Hospital, Slovenj Gradec, Slovenia. 89Unit of Infectious Diseases, University General Hospital of Alexandroupolis, Democritus University Thrace, Dragana, Greece. Correspondence: Jonathan S. Nguyen-Van-Tam, University of Nottingham, City Hospital, DM, Room A28b, Clinical Sciences Building, Nottingham NG5 1PB, UK. E-mail: jvt@nottingham.ac.uk *List of PRIDE Consortium Investigators are in Appendix 1. For affiliations, please see Table S1. Múltipla - ver em notas Background The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1) pdm09 virus infection. Methods A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A (H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results Of 20 634 included participants, 5978 (29 0%) had IRP; conversely, 3349 (16 2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0 83 (95% CI 0 64–1 06; P = 0 136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0 72 (0 44–1 17; P = 0 180)] or likelihood of requiring ventilatory support [adj. OR = 1 17 (0 71– 1 92; P = 0 537)], but early treatment versus later significantly reduced mortality [adj. OR = 0 70 (0 55–0 88; P = 0 003)] and likelihood of requiring ventilatory support [adj. OR = 0 68 (0 54– 0 85; P = 0 001)]. Conclusions Early NAI treatment of patients hospitalised with A (H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Published
2016

11. Reply to Jones et al.

Author

Venkatesan, Sudhir, Myles, Puja R., Memish, Ziad, and Nguyen-Van-Tam, Jonathan S.

Subjects
*NEURAMINIDASE, *HOSPITAL care
Published
2017
Full Text
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12. 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

Author

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, Y-S, 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, Aguiar-Oliveira, ML, Al Masri, M, Amin, R, Araújo, WN, Ballester-Orcal, E, Bantar, C, Bao, J, Barhoush, MM, Basher, A, Bautista, E, Bettinger, J, Bingisser, R, Bouza, E, Bozkurt, I, Celjuska-Tošev, E, Chan, KKC, Chen, Y, Chinbayar, T, Cilloniz, C, Cox, RJ, Cuezzo, MR, Cui, W, Dashti-Khavidaki, S, du, B, El Rhaffouli, H, Escobar, H, Florek-Michalska, A, Fraser, J, Gerrard, J, Gormley, S, Götberg, S, Hoffmann, M, Honarvar, B, Hu, J, Kemen, C, Khandaker, G, Koay, KSC, Kojic, M, Kyaw, WM, Leibovici, L, Li, H, Li, X-L, Libster, R, Loh, TP, Macbeth, D, Maltezos, E, Manabe, T, Marcone, DN, Marczynska, M, Mastalir, FP, Moghadami, M, Moriconi, L, Ozbay, B, Pečavar, B, Poeppl, W, Poliquin, PG, Rahman, M, Rascon-Pacheco, A, Refaey, S, Schweiger, B, Smith, FG, Somer, A, Souza, TML, Tabarsi, P, Tripathi, CB, Velyvyte, D, Viasus, D, Yu, Q, Yuen, K-Y, Zhang, W, Zuo, W, Pediatric surgery, CCA - Innovative therapy, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S. A., Al Mamun, Adbullah, Anovadiya, Ashish P., Azziz-Baumgartner, Eduardo, Báez, Clarisa, Bassetti, Matteo, Beovic, Bojana, Bertisch, Barbara, Bonmarin, Isabelle, Booy, Robert, Borja-Aburto, Victor H., Burgmann, Heinz, Cao, Bin, Carratala, Jordi, Denholm, Justin T., Dominguez, Samuel R., Duarte, Pericles A.D., Dubnov-Raz, Gal, Echavarria, Marcela, Fanella, Sergio, Gao, Zhancheng, Gérardin, Patrick, Giannella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Higuera Iglesias, Anjarath L., Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Ilija, Kwan, Arthur M. C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B., Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Fari, Mayo-Montero, Elga, Mcgeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikic, Dragan, Mohn, Kristin G.I., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Ozkan, Mehpare, Parekh, Dhruv, Paul, Mical, Polack, Fernando P., Rath, Barbara A., Rodríguez, Alejandro H., Sarrouf, Elena B., Seale, Anna C., Sertogullarindan, Bunyamin, Siqueira, Marilda M., Skret-Magierlo, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K.W., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., van Zwol, Annelie, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, Nguyen-van-Tam, Jonathan S, Aguiar-Oliveira, Maria de Lourde, Al Masri, Malakita, Amin, Robed, Araújo, Wildo N., Ballester-Orcal, Elena, Bantar, Carlo, Bao, Jing, Barhoush, Mazen M., Basher, Ariful, Bautista, Edgar, Bettinger, Julie, Bingisser, Roland, Bouza, Emilio, Bozkurt, Ilkay, Celjuska-Tošev, Elvira, Chan, Kenny K.C., Chen, Yusheng, Chinbayar, Tserendorj, Cilloniz, Catia, Cox, Rebecca J., Cuezzo, María R., Cui, Wei, Dashti-Khavidaki, Simin, Du, Bin, El Rhaffouli, Hicham, Escobar, Hernan, Florek-Michalska, Agnieszka, Fraser, Jame, Gerrard, John, Gormley, Stuart, Götberg, Sandra, Hoffmann, Matthia, Honarvar, Behnam, Hu, Jianmin, Kemen, Christoph, Khandaker, Gulam, Koay, Evelyn S. C., Kojic, Miroslav, Kyaw, Win M., Leibovici, Leonard, Li, Hongru, Li, Xiao-Li, Libster, Romina, Loh, Tze P., Macbeth, Deborough, Maltezos, Efstratio, Manabe, Toshie, Marcone, Débora N., Marczynska, Magdalena, Mastalir, Fabiane P., Moghadami, Mohsen, Moriconi, Lilian, Ozbay, Bulent, Pečavar, Blaž, Poeppl, Wolfgang, Poliquin, Philippe G., Rahman, Mahmudur, Rascon-Pacheco, Alberto, Refaey, Samir, Schweiger, Brunhilde, Smith, Fang G., Somer, Ayper, Souza, Thiago M. L., Tabarsi, Payam, Tripathi, Chandrabhanu B., Velyvyte, Daiva, Viasus, Diego, Yu, Qin, Yuen, Kwok-Yung, Zhang, Wei, and Zuo, Wei

Subjects
Male, ANTIVIRAL TREATMENT, IMPACT, Respiratory System, CHILDREN, Neuraminidase inhibitors, Pandemic influenza, Mortality, Meta-analysis, medicine.disease_cause, THERAPY, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, 0302 clinical medicine, Pandemic, Influenza A Virus, Influenza A virus, Zanamivir, 030212 general & internal medicine, Enzyme Inhibitors, Child, OUTCOMES, 0303 health sciences, biology, Neuraminidase inhibitor, Medicine (all), virus diseases, Middle Aged, 3. Good health, Hospitalization, Treatment Outcome, Female, Life Sciences & Biomedicine, Adolescent, Adult, Antiviral Agents, Humans, Influenza, Human, Neuraminidase, Oseltamivir, Proportional Hazards Models, Young Adult, Pandemics, Pulmonary and Respiratory Medicine, Human, medicine.drug, medicine.medical_specialty, medicine.drug_class, PANDEMIC INFLUENZA, Article, PRIDE Consortium Investigators, 03 medical and health sciences, Critical Care Medicine, General & Internal Medicine, Internal medicine, medicine, H1N1 Subtype, Intensive care medicine, Science & Technology, 030306 microbiology, business.industry, STEM-CELL TRANSPLANTATION, ADULTS, Odds ratio, Influenza, chemistry, RISK-FACTORS, biology.protein, business
Abstract

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 29234 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

Published
2014

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