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3. Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU

Author

Otten, Marieke H., Buysse, Corinne M. P., Buddingh, Emmeline P., Terheggen-Lagro, Suzanne W. J., von Asmuth, Erik G. J., de Sonnaville, Eleonore S. V., Ketharanathan, Naomi, Bunker-Wiersma, Heleen E., Haverman, Lotte, Hogenbirk, Karin, de Hoog, Matthijs, Humblet, Martien, Joosten, Koen F. M., Kneyber, Martin C. J., Krabben, Geanne, Lemson, Joris, Maas, Nienke M., Maebe, Sofie, Roeleveld, Peter P., van Schooneveld, Monique, Timmers-Raaijmaakers, Brigitte, van Waardenburg, Dick, Walker, Jennifer C., Wassenberg, Renske, van Woensel, Job B. M., de Wit, Esther, Wolthuis, Diana W., van Zwol, Annelies, Oostrom, Kim J., Knoester, Hennie, and Dulfer, Karolijn

Published
2023
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4. Potentially Life-Threatening Interaction between Opioids and Intrathecal Baclofen in Individuals with a Childhood-Onset Neurological Disorder: A Case Series and Review of the Literature.

Author

van Dijk, Liza M.M., van Zwol, Annelies, Buizer, Annemieke I., van de Pol, Laura A., Slot, K. Mariam, de Wildt, Saskia N., and Bonouvrié, Laura A.

Subjects
*LITERATURE reviews, *NEUROLOGICAL disorders, *DRUG interactions, *CENTRAL nervous system, *RESPIRATORY insufficiency
Abstract

Background Spasticity and dystonia are movement impairments that can occur in childhood-onset neurological disorders. Severely affected individuals can be treated with intrathecal baclofen (ITB). Concomitant use of ITB and opioids has been associated with central nervous system (CNS) depression. This study aims to describe the clinical management of this interaction, based on a case series and review of literature. Methods Four individuals with childhood-onset CNS disorders (age 8–24) and CNS-depressant overdose symptoms after the concomitant use of ITB and opioids are described. The Drug Interaction Probability Scale (DIPS) was calculated to assess the cause-relationship (doubtful <2, possible 2–4, probable 5–8, and highly probable >8) of the potential drug–drug interaction. A literature review of similar previously reported cases and the possible pharmacological mechanisms of opioid–baclofen interaction is provided. Results After ITB and opioid co-administration, three out of four patients had decreased consciousness, and three developed respiratory depression. DIPS scores indicated a possible cause-relationship in one patient (DIPS: 4) and a probable cause-relationship in the others (DIPS: 6, 6, and 8). Discontinuation or adjusting ITB or opioid dosages resulted in clinical recovery. All patients recovered completely. In the literature, two articles describing nine unique cases were found. Conclusion Although the opioid–ITB interaction is incompletely understood, concomitant use may enhance the risk of symptoms of CNS-depressant overdose, which are potentially life-threatening. If concomitant use is desirable, we strongly recommend to closely monitor these patients to detect interaction symptoms early. Awareness and monitoring of the potential opioid–ITB interaction is essential to reduce the risk of severe complications. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Mobilization practices in critically ill children: a European point prevalence study (EU PARK-PICU)

Author

Ista, Erwin, Scholefield, Barnaby R., Manning, Joseph C., Harth, Irene, Gawronski, Orsola, Bartkowska-Śniatkowska, Alicja, Ramelet, Anne-Sylvie, Kudchadkar, Sapna R., Ritson, Paul C., Nikolaou, Filippia, de Neef, Marjorie, Kneyber, Martin, Penny-Thomas, Kate, Linton, Christina, Balmaks, Reinis, Richter, Matthias, Chiusolo, Fabrizio, Cecchetti, Corrado, Roberti, Marco, di Furia, Michela, Grandjean, Chantal, Nygaard, Bettina, Lopez, Yolanda, Koroglu, Tolga, Besci, Tolga, Mora, Roberta Da Rin Della, Agbeko, Rachel S., Borrows, Emma, Bochaton, Nathalie, Mattsson, Janet, Ksellmann, Anne, Hero, Barbara, Rosada-Kurasinska, Jowita, Świder, Magdalena, Bonaldi, Amabile, Giugni, Cristina, Oruganti, Siva, Gates, Simon, Smith, Hazel, van Zwol, Annelies, Hills, Jenna, Conroy, Johanna, Bebbington, Mark, Neunhoeffer, Felix, Duval, Els, EU PARK-PICU Collaborators, Internal Medicine, Pediatric Surgery, Ritson, P.C., Nikolaou, F., de Neef, M., Kneyber, M., Penny-Thomas, K., Linton, C., Balmaks, R., Richter, M., Chiusolo, F., Cecchetti, C., Roberti, M., Di Furia, M., Grandjean, C., Nygaard, B., Lopez, Y., Koroglu, T., Besci, T., Mora, RDRD, Agbeko, R.S., Borrows, E., Bochaton, N., Mattsson, J., Ksellmann, A., Hero, B., Rosada-Kurasinska, J., Świder, M., Bonaldi, A., Giugni, C., Oruganti, S., Gates, S., Smith, H., van Zwol, A., Hills, J., Conroy, J., Bebbington, M., Neunhoeffer, F., Duval, E., Nursing, and Paediatric Intensive Care

Subjects
Male, Occupational therapy, medicine.medical_specialty, Time Factors, Critical Illness, medicine.medical_treatment, Developmental paediatrics, Prevalence, Intensive Care Units, Pediatric, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Odds Ratio, medicine, Humans, Child, Contraindication, Early Ambulation, Mechanical ventilation, Intensive care units, Rehabilitation, Mobilization, Critically ill, business.industry, Research, Infant, Newborn, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Infant, 030208 emergency & critical care medicine, Paediatrics, lcsh:RC86-88.9, Europe, Critical care, Cross-Sectional Studies, 030228 respiratory system, Child, Preschool, Emergency medicine, Female, Human medicine, business, Physical therapy
Abstract

Background Early mobilization of adults receiving intensive care improves health outcomes, yet little is known about mobilization practices in paediatric intensive care units (PICUs). We aimed to determine the prevalence of and factors associated with physical rehabilitation in PICUs across Europe. Methods A 2-day, cross-sectional, multicentre point prevalence study was conducted in May and November 2018. The primary outcome was the prevalence of physical therapy (PT)- or occupational therapy (OT)-provided mobility. Clinical data and data on patient mobility, potential mobility safety events, and mobilization barriers were prospectively collected in patients admitted for ≥72 h. Results Data of 456 children admitted to one of 38 participating PICUs from 15 European countries were collected (456 patient days); 70% were under 3 years of age. The point prevalence of PT- and/or OT-provided mobility activities was 39% (179/456) (95% CI 34.7–43.9%) during the patient days, with significant differences between European regions. Nurses were involved in 72% (924/1283) of the mobility events; in the remaining 28%, PT/OT, physicians, family members, or other professionals were involved. Of the factors studied, family presence was most strongly positively associated with out-of-bed mobilization (aOR 7.83, 95% CI 3.09–19.79). Invasive mechanical ventilation with an endotracheal tube was negatively associated with out-of-bed mobility (aOR 0.28, 95% CI 0.12–0.68). Patients were completely immobile on 25% (115/456) of patient days. Barriers to mobilization were reported on 38% of patient days. The most common reported patient-related barriers were cardiovascular instability (n = 47, 10%), oversedation (n = 39, 9%), and medical contraindication (n = 37, 8%). Potential safety events occurred in 6% of all documented mobilization events. Conclusion Therapists are infrequently consulted for mobilization of critically ill children in European PICUs. This study highlights the need for a systematic and interdisciplinary mobilization approach for critically ill children. Graphical abstract

Published
2020

17. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an IPD meta-analysis

Author

Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Lim, Wei Shen, Mamun, Abdullah Al, Anovadiya, Ashish P., Araújo, Wildo N., Azziz-Baumgartner, Eduardo, Báez, Clarisa, Bantar, Carlos, Barhoush, Mazen M., Bassetti, Matteo, Beović, 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, Hu, Xiaoyun, 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., Skręt-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, and Nguyen-Van-Tam, Jonathan S.

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 (IPD) 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 influenza-related pneumonia (IRP). Odds ratios (OR) were estimated using generalized linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. ----- RESULTS: Among 20,634 included participants, 5,978 (29.0%) had IRP; conversely, 3,349 (16.2%) had confirmed 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 5,978 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
2015
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18. 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, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, Anovadiya, Ashish P., Azziz-Baumgartner, Eduardo, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Miki?, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, Mehpare, Parekh, Dhruv, Paul, Mical, Polack, Fernando P., Rath, Barbara A., Sarrouf, Elena B., Seale, Anna C., Sertogullarindan, Bunyamin, Siqueira, Marilda M., Skr?t-Magier?o, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, and Nguyen-Van-Tam, Jonathan

Abstract

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

Published
2014

19. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: an individual participant data meta-analysis

Author

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, Iglesias, Anjarath L. H., 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 L., Langenegger, Eduard, Lankarani, Kamran B., Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Auksė, Mikić, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K. W., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T. C., Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan S., Département des maladies infectieuses, Institut de Veille Sanitaire (INVS), Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Diseases, Peking University People's Hospital, Réanimation médicale néonatale et pédiatrique, CHR la Reunion site Sud, CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), National Perinatal Epidemiology Unit, University of Oxford [Oxford], 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), and University of Oxford

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Abstract

International audience; 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

Published
2014
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26. 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, Hu, Xiaoyun, 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., Skręt‐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., 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, Hu, Xiaoyun, 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., Skręt‐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, and Nguyen-Van-Tam, Jonathan S.

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.

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27. 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, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, and Nguyen-Van-Tam, Jonathan

Abstract

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 associat

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28. 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, Hu, Xiaoyun, 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., Skręt‐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., 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, Hu, Xiaoyun, 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., Skręt‐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, and Nguyen-Van-Tam, Jonathan S.

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.

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29. 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, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, and Nguyen-Van-Tam, Jonathan

Abstract

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 associat

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30. 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, Hu, Xiaoyun, 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., Skręt‐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., 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, Hu, Xiaoyun, 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., Skręt‐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, and Nguyen-Van-Tam, Jonathan S.

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.

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31. 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, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, and Nguyen-Van-Tam, Jonathan

Abstract

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 associat

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32. 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, Hu, Xiaoyun, 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., Skręt‐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., 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, Hu, Xiaoyun, 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., Skręt‐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, and Nguyen-Van-Tam, Jonathan S.

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.

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33. 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, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, and Nguyen-Van-Tam, Jonathan

Abstract

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 associat

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34. 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, Hu, Xiaoyun, 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., Skręt‐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., 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, Hu, Xiaoyun, 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., Skręt‐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, and Nguyen-Van-Tam, Jonathan S.

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.

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35. 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, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, Nguyen-Van-Tam, Jonathan, Muthuri, Stella G., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Al Khuwaitir, Tarig S., Al Mamun, Abdullah, 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, Gianella, Maddalena, Gubbels, Sophie, Herberg, Jethro, Iglesias, Anjarath L. Higuera, Hoger, Peter H., Hu, Xiaoyun, Islam, Quazi T., Jiménez, Mirela F., Kandeel, Amr, Keijzers, Gerben, Khalili, Hossein, Knight, Marian, Kudo, Koichiro, Kusznierz, Gabriela, Kuzman, Iljia, Kwan, Arthur M.C., Amine, Idriss Lahlou, Langenegger, Eduard, Lankarani, Kamran B, Leo, Yee-Sin, Linko, Rita, Liu, Pei, Madanat, Faris, Mayo-Montero, Elga, McGeer, Allison, Memish, Ziad, Metan, Gokhan, Mickiene, Aukse, Mikić, Dragan, Mohn, Kristin G., Moradi, Ahmadreza, Nymadawa, Pagbajabyn, Oliva, Maria E., Oskan, 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., Skręt-Magierło, Joanna, Stephan, Frank, Talarek, Ewa, Tang, Julian W., To, Kelvin K., Torres, Antoni, Törün, Selda H., Tran, Dat, Uyeki, Timothy M., Van Zwol, Annelies, Vaudry, Wendy, Vidmar, Tjasa, Yokota, Renata T.C., Zarogoulidis, Paul, and Nguyen-Van-Tam, Jonathan

Abstract

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 associat

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36. 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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37. 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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38. [An infant with meningitis caused by resistant pneumococcus: infection despite vaccination].

Author

van der Meer H, van Zwol A, Spanjaard L, and van Furth M

Subjects
Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Ceftriaxone pharmacology, Ceftriaxone therapeutic use, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Infant, Male, Meningitis, Pneumococcal prevention & control, Microbial Sensitivity Tests, Serotyping, Vancomycin pharmacology, Vancomycin therapeutic use, Drug Resistance, Multiple, Bacterial, Meningitis, Pneumococcal diagnosis, Pneumococcal Vaccines administration & dosage, Streptococcus pneumoniae classification, Streptococcus pneumoniae drug effects, Streptococcus pneumoniae immunology
Abstract

Background: Following the introduction of a heptavalent pneumococcal conjugate vaccine (PCV7) in the Netherlands in 2006, the incidence of invasive pneumococcal disease (IPD) declined significantly. Since then a shift towards non-vaccine serotype IPD has been noted., Case Description: We present the case of multidrug resistant non-vaccine serotype 19A pneumococcal meningitis in a 5-month-old boy. He was admitted to our Paediatric Intensive Care Unit (PICU) with seizures and septic shock. A barbiturate-induced coma was eventually required to control the seizures; shock was combated with intravenous fluids and inotropes. He received a 6-week course of ceftriaxone and vancomycin. At follow-up, one year after discharge, he had unilateral deafness and minor developmental delay., Conclusion: Worldwide, pneumococcal serotype 19A is now the most common cause of IPD in children, with an increasing incidence of multidrug resistant strains. This trend has not yet been observed in the Netherlands. This case demonstrates that even following the introduction of PCV7 pneumococcal meningitis can still occur. Prompt recognition of the symptoms is still essential.

Published
2012

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