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301. Correction to Practical Indicators for Risk of Airborne Transmission in Shared Indoor Environments and Their Application to COVID-19 Outbreaks

Author: Peng, Zhe, Pineda Rojas, Andrea L., Kropff, Emilio, Bahnfleth, William, Buonanno, Giorgio, Dancer, Stefanie J., Kurnitski, Jarek, Li, Yuguo, Loomans, Marcel G.L.C., Marr, Linsey C., Morawska, Lidia, Nazaroff, William, Noakes, Catherine, Querol, Xavier, Sekhar, Chandra, Tellier, Raymond, Greenhalgh, Trisha, Bourouiba, Lydia, Boerstra, Atze, Tang, Julian W., Miller, Shelly L., and Jimenez, Jose L.
Published: 2022
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302. Correlations between climate factors and incidence-a contributor to RSV seasonality.

Author: Tang, Julian W. and Loh, Tze Ping
Abstract: SUMMARY Respiratory syncytial virus is the most common respiratory virus infection in early childhood, causing a wide range of illness from mild colds to life-threatening croup, bronchiolitis and pneumonia that may require intensive care. Exactly which parameters contribute to the seasonality of RSV (and other respiratory viruses, such as influenza) and their comparative significance are the subject of ongoing intensive debate. This review article summarises the specific contributions and correlations between the incidence of RSV and various climate parameters. This systematic review of the literature specifically focuses on these climate associations and have been stratified by study site latitudes: tropical (0-23.5°N or S), subtropical (23.5-40°N or S) and temperate latitudes (>40°N or S). Correlations between RSV incidence and temperature and relative humidity are particularly variable and inconsistent amongst the tropical regions. In subtropical and temperate regions, RSV incidence is more consistently positively correlated with lower temperatures and higher relative humidity. Although there is some variation with the diagnostic methods used in these studies, most used immunofluorescent viral antigen testing to diagnose RSV infection. Statistically, most studies used some form of regression analysis, which assumes no dependence between data taken at different time points. A few used the autoregressive integrated moving average approach, which may be more realistic for an infectious agent as the total number of cases usually evolves in a time-dependent manner during a typical seasonal epidemic. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
Published: 2014
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303. Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulin.

Author: Ma, Christine, Wong, Chun K., Wong, Bonnie C.K., Chan, K.C. Allen, Lun, Samantha W.M., Lee, Nelson, Wu, Justin, Cockram, Clive S., Chan, Paul K.S., and Tang, Julian W.
Abstract: Viral loads and cytokine responses Epstein-Barr virus (EBV) were measured in an 18-year-old boy with severe glandular fever complicated by a mild anaemia, severe thrombocytopaenia and neutropaenia. Hepatosplenomegaly was detected by abdominal ultrasound in the presence of significant hepatitis. Cytokine testing demonstrated elevated cell-mediated Th1 (IFN-γ, IL-12, sTNFR1, CXCL10, CXCL9 and CCL3) and humoral Th2 (IL-4) immune responses. Serum antibodies to EBV virus capsid antigen (VCA) IgM and IgG antibodies were detected, together with a raised EBV DNA level (up to about 70,000 DNA copies/mL) in the acute phase of the illness. This EBV DNA load decreased rapidly in response to treatment with a combination of foscarnet, intravenous immunoglobulin and prednisolone, and the boy's symptoms settled eventually after approximately 50 days of illness, following this combined antiviral and immune-modulating therapy. Detailed immunological, virological, haematological and biochemical laboratory parameters are presented to document this patient's severe EBV disease and eventual recovery. J. Med. Virol. 81:99-105, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
Published: 2009
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304. An exploration of the political, social, economic and cultural factors affecting how different global regions initially reacted to the COVID-19 pandemic

Author: Tang, Julian W., Caniza, Miguela A., Dinn, Mike, Dwyer, Dominic E., Heraud, Jean-Michel, Jennings, Lance C., Kok, Jen, Kwok, Kin On, Li, Yuguo, Loh, Tze Ping, Marr, Linsey C., Nara, Eva Megumi, Perera, Nelun, Saito, Reiko, Santillan-Salas, Carlos, Sullivan, Sheena, Warner, Matt, Watanabe, Aripuanã, and Zaidi, Sabeen Khurshid
Abstract: Responses to the early (February–July 2020) COVID-19 pandemic varied widely, globally. Reasons for this are multiple but likely relate to the healthcare and financial resources then available, and the degree of trust in, and economic support provided by, national governments. Cultural factors also affected how different populations reacted to the various pandemic restrictions, like masking, social distancing and self-isolation or self-quarantine. The degree of compliance with these measures depended on how much individuals valued their needs and liberties over those of their society. Thus, several themes may be relevant when comparing pandemic responses across different regions. East and Southeast Asian populations tended to be more collectivist and self-sacrificing, responding quickly to early signs of the pandemic and readily complied with most restrictions to control its spread. Australasian, Eastern European, Scandinavian, some Middle Eastern, African and South American countries also responded promptly by imposing restrictions of varying severity, due to concerns for their wider society, including for some, the fragility of their healthcare systems. Western European and North American countries, with well-resourced healthcare systems, initially reacted more slowly, partly in an effort to maintain their economies but also to delay imposing pandemic restrictions that limited the personal freedoms of their citizens.
Published: 2022
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305. The role of SARS-CoV-2 aerosol transmission during the COVID-19 pandemic

Author: Tang, Julian W., Marr, Linsey C., Li, Yuguo, and Eames, Ian
Abstract: The COVID-19 pandemic, caused by the virus SARS-CoV-2, has touched most parts of the world and devastated the lives of many. The high transmissibility coupled with the initial poor outcome for the elderly led to crushingly high fatalities. The scientific response to the pandemic has been formidable, aided by advancements in virology, computing, data analysis, instrumentation, diagnostics, engineering and infection control. This has led to improvements in understanding and has helped to challenge some established orthodoxies. Sufficient time has elapsed since the start of the COVID-19 pandemic that a clearer view has emerged about transmission and infection risks, public health responses and related societal and economic impacts. This timely volume has provided an opportunity for the science community to report on these new developments.
Published: 2022
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306. Outbreak of SARS-CoV-2 at a hospice: terminated after the implementation of enhanced aerosol infection control measures

Author: Feathers, Luke, Hinde, Tracey, Bale, Tammy, Hyde, Jo, Bird, Paul W., Holmes, Christopher W., and Tang, Julian W.
Abstract: Outbreaks of COVID-19 in hospices for palliative care patients pose a unique and difficult situation. Staff, relatives and patients may be possible sources and recipients of infection. We present an outbreak of COVID-19 in a hospice setting, during the UK's first pandemic wave. During the outbreak period, 26 patients and 30 staff tested SARS-CoV-2 positive by laboratory-based RT-PCR testing. Most infected staff exhibited some mild, non-specific symptoms so affected staff members may not have voluntarily self-isolated or had themselves tested on this basis. Similarly, for infected patients, most became symptomatic and were then isolated. Additional, enhanced aerosol infection control measures were implemented, including opening of all windows where available; universal masking for all staff, including in non-clinical areas and taking breaks separately; screening for asymptomatic infection among staff and patients, with appropriate isolation (at home for staff) if infected; performing a ventilation survey of the hospice facility. After these measures were instigated, the numbers of COVID-19 cases decreased to zero over the following three weeks. This outbreak study demonstrated that an accurate understanding of the routes of infection for a new pathogen, as well as the nature of symptomatic versus asymptomatic infection and transmission, is crucial for controlling its spread.
Published: 2022
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307. Comparative evaluation of 2 automated molecular systems for the detection of HSV-1 and 2 from genital swab specimens.

Author: May, Shoshanna and Tang, Julian W.
Subjects: *HERPES simplex virus, *MICROBIOLOGICAL assay, *HERPES genitalis treatment, *HERPES simplex transmission, *IMMUNOGOLD labeling
Abstract: Abstract BD ProbeTec HSV 1 & 2 Qx (on the BD Viper XTR) and the Aptima HSV 1 & 2 (on the Hologic Panther) assays were compared. Of 257 clinical samples, 96.6% positive and 88.5% negative results were concordant, respectively. The BD assay was more sensitive than the Aptima, but the latter was more specific. Highlights • Diagnosing of HSV 1 & 2 genital herpes is important for treatment and contact tracing. • BD ProbeTec HSV 1 & 2 Qx is an automated assay that runs on the BD Viper XTR platform. • Aptima HSV 1 & 2 is an automated assay that runs on the Hologic Panther platform. • Of 257 samples tested on both, 88.5% negatives and 96.6% positives were concordant. • The BD ProbeTec was also more sensitive but less specific than the Aptima 1 & 2 assay [ABSTRACT FROM AUTHOR]
Published: 2019
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308. SARS-CoV-2 and aerosols—Arguing over the evidence.

Author: Tang, Julian W.
Subjects: *MICROBIOLOGICAL aerosols, *COVID-19, *AIRBORNE infection
Abstract: This Commentary discusses various aspects around the controversial issue of SARSCoV-2 and aerosol transmission, highlighting certain counter arguments and explaining why they are invalid. [ABSTRACT FROM AUTHOR]
Published: 2021
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309. Publisher Correction to: COVID-19: interpreting scientific evidence - uncertainty, confusion and delays.

Author: Tang, Julian W.
Subjects: *COVID-19, *UNCERTAINTY, *EVIDENCE
Abstract: An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]
Published: 2020
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310. COVID-19: interpreting scientific evidence – uncertainty, confusion and delays.

Author: Tang, Julian W
Subjects: *COVID-19, *SARS disease, *MEDICAL personnel, *MERS coronavirus, *AIRBORNE infection, *SARS-CoV-2
Abstract: COVID-19: interpreting scientific evidence - uncertainty, confusion and delays The author identified three errors in the article body: The typo "SARS-CoV-12,003", should be written as "SARS-CoV-1, 2003": i. in the 1st page, right-hand column, 2nd paragraph and ii. in the 2nd page, right-hand column, 4th paragraph; In the last paragraph "SARS-CoV-2, 2003" should be written as "SARS-CoV-1, 2003". One of the emerging aspects of the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) pandemic, is how different governments and institutions interpret and apply the same scientific evidence. There were other less dramatic examples of such reversals based on "mounting evidence", such as whether or not asymptomatic SARS-CoV-2 infections truly existed - then whether or not they could transmit the virus [[26]-[28]]; and whether SARS-CoV-2 was airborne or not - and whether it could be transmitted by exhaled aerosols [[29]-[32]]. [Extracted from the article]
Published: 2020
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311. Association between meteorological variations and activities of influenza A and B across different climate zones: a multi-region modelling analysis across the globe.

Author: Chong, Ka Chun, Lee, Tsz Cheung, Chen, Jian, Choy, Wisely S C, Krajden, Mel, Jalal, Hamid, Jennings, Lance, Alexander, Burmaa, Lee, Hong Kai, Fraaij, Pieter, Levy, Avram, Yeung, Apple C M, Tozer, Sarah, Lau, Steven Y F, Jia, Katherine M, Tang, Julian W T, Hui, David S C, Chan, Paul K S, Bialasiewicz, Seweryn, and Smith, David W
Abstract: Objective: To elucidate the effects of meteorological variations on the activity of influenza A and B in 11 sites across different climate regions.Methods: Daily numbers of laboratory-confirmed influenza A and B cases from 2011-2015 were collected from study sites where the corresponding daily mean temperature, relative humidity, wind speed and daily precipitation amount were used for boosted regression trees analysis on the marginal associations and the interaction effects.Results: Cold temperature was a major determinant that favored both influenza A and B in temperate and subtropical sites. Temperature-to-influenza A, but not influenza B, exhibited a U-shape association in subtropical and tropical sites. High relative humidity was also associated with influenza activities but was less consistent with influenza B activity. Compared with relative humidity, absolute humidity had a stronger association - it was negatively associated with influenza B activity in temperate zones, but was positively associated with both influenza A and B in subtropical and tropical zones.Conclusion: The association between meteorological factors and with influenza activity is virus type specific and climate dependent. The heavy influence of temperature on influenza activity across climate zones implies that global warming is likely to have an impact on the influenza burden. [ABSTRACT FROM AUTHOR]
Published: 2019
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312. Editorial: the airborne microbiome - implications for aerosol transmission and infection control - special issue.

Author: Tang, Julian W. and Li, Yuguo
Subjects: *INFECTIOUS disease transmission, *INFECTION prevention, *AEROSOLS, *DRUG resistance, *RESEARCH funding, *AIR microbiology, *PREVENTION of communicable diseases, *RESPIRATION, *RESPIRATORY infections, RESPIRATORY organ microbiology
Abstract: Although the title of the Special Issue is 'Airborne Microbiome' the manuscripts received have highlighted a variety of peripheral, yet related aspects of this. The contributions are a mixture of primary research, reviews and commentaries, including: new methods to explore environmental niches where such microbes may grow, their detection and characterisation in the human host, which pathogens are present in the respiratory tract and can be exhaled in human breath to potentially spread via the airborne route, and some strategies for their control. Finally, a historical-to-current overview explores human-microbial interactions, including problems with sampling and detection methods, drug resistance, the role of super-spreaders and issues around research funding. [ABSTRACT FROM AUTHOR]
Published: 2019
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313. Why has the COVID-19 pandemic generated such global interest from the engineering community?

Author: Tang, Julian W. and Licina, Dusan
Subjects: emergence

314. Derivation of humidity equation from Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence

Author: Marr, Linsey C., Tang, Julian W., Mullekom, Jennifer Van, and Lakdawala, Seema S.
Subjects: 13. Climate action
Abstract: Influenza incidence and seasonality, along with virus survival and transmission, appear to depend at least partly on humidity, and recent studies have suggested that absolute humidity (AH) is more important than relative humidity (RH) in modulating observed patterns. In this perspective article, we re-evaluate studies of influenza virus survival in aerosols, transmission in animal models and influenza incidence to show that the combination of temperature and RH is equally valid as AH as a predictor. Collinearity must be considered, as higher levels of AH are only possible at higher temperatures, where it is well established that virus decay is more rapid. In studies of incidence that employ meteorological data, outdoor AH may be serving as a proxy for indoor RH in temperate regions during the wintertime heating season. Finally, we present a mechanistic explanation based on droplet evaporation and its impact on droplet physics and chemistry for why RH is more likely than AH to modulate virus survival and transmission.

315. Derivation of humidity equation from Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence

Author: Marr, Linsey C., Tang, Julian W., Mullekom, Jennifer Van, and Lakdawala, Seema S.
Subjects: 13. Climate action
Abstract: Influenza incidence and seasonality, along with virus survival and transmission, appear to depend at least partly on humidity, and recent studies have suggested that absolute humidity (AH) is more important than relative humidity (RH) in modulating observed patterns. In this perspective article, we re-evaluate studies of influenza virus survival in aerosols, transmission in animal models and influenza incidence to show that the combination of temperature and RH is equally valid as AH as a predictor. Collinearity must be considered, as higher levels of AH are only possible at higher temperatures, where it is well established that virus decay is more rapid. In studies of incidence that employ meteorological data, outdoor AH may be serving as a proxy for indoor RH in temperate regions during the wintertime heating season. Finally, we present a mechanistic explanation based on droplet evaporation and its impact on droplet physics and chemistry for why RH is more likely than AH to modulate virus survival and transmission.

316. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Author: Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., Nguyen-Van-Tam, Jonathan S., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., and Nguyen-Van-Tam, Jonathan S.
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.
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317. 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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318. 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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319. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Author: Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., Nguyen-Van-Tam, Jonathan S., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., and Nguyen-Van-Tam, Jonathan S.
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.
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320. 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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321. 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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322. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Author: Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., Nguyen-Van-Tam, Jonathan S., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., and Nguyen-Van-Tam, Jonathan S.
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.
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323. 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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324. 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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325. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Author: Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., Nguyen-Van-Tam, Jonathan S., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., and Nguyen-Van-Tam, Jonathan S.
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.
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326. 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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327. 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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328. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Author: Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., Nguyen-Van-Tam, Jonathan S., Venkatesan, Sudhir, Myles, Puja R., Leonardi-Bee, Jo, Muthuri, Stella G., Al Masri, Malak, Andrews, Nick, Bantar, Carlos, Dubnov-Raz, Gal, Gérardin, Patrick, Koay, Evelyn S.C., Loh, Tze Ping, Memish, Ziad A., Miller, Elizabeth, Oliva, Maria E., Rath, Barbara A., Schweiger, Brunhilde, Tang, Julian W., Tran, Dat, Vidmar, Tjasa, Waight, Pauline A., and Nguyen-Van-Tam, Jonathan S.
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.
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329. 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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330. 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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331. Case presentation: persistent adenovirus B3 infections associated with bronchiolitis obliterans treated with cidofovir in a child with mosaic tetrasomy 9p.

Author: Ions, Rhiannon, Narayanan, Manjith, Browning, Michael, Gaillard, Erol A., Stiefel, Gary, and Tang, Julian W.
Subjects: ADENOVIRUSES, DNA viruses, BRONCHIOLITIS, LUNG diseases, PNEUMONIA treatment, ANTIVIRAL agents
Abstract: Background: Adenoviruses (AdV) are non-enveloped, double-stranded DNA viruses with multiple serotypes, which cause a variety of end-organ disease in both immunocompetent and immunocompromised individuals. Some adenoviruses can become latent in the mucosa-associated lymphoid tissue (e.g. adenoids and tonsils), with the potential to reactivate sporadically, leading to upper or lower respiratory tract infection and disease. Bronchiolitis Obliterans (BO) is a rare chronic lung disorder which usually follows a severe insult to the respiratory tract. In children, it is a complication of severe infections (as post-infectious BO), typically manifesting after a severe respiratory infection, in previously healthy pre-school children. Symptoms and signs of air trapping (hyperinflated chest, expiratory wheeze) with persistent oxygen requirement are characteristic. The presence of the unusual mosaic tetrasomy 9p genotype in this case, despite standard cidofovir therapy for persistent or chronic adenovirus infection, may have impacted on the child's long-term clinical outcomes.Case Presentation: We present a case of persistent AdV B3 infection in a 14-month old boy with mosaic tetrasomy 9p, which persisted for 10 weeks, resulting in radiologically-confirmed BO, requiring cidofovir to control the persistent AdV B3 infection and standard therapy with pulsed steroids. We argue that in the presence of the mosaic tetrasomy 9p, earlier antiviral therapy may have decreased the severity of BO, as this mutation is known to be associated with some degree of immune dysregulation.Conclusions: Adenovirus infections are common in children and may persist as latent infections, with subsequent reactivations during loss of immune control, related to systemic illness arising from other causes. In chronic, reactivated AdV infection with pneumonia, BO is a recognised complication. However, in this case, with the presence of the mosaic tetrasomy 9p mutation, earlier antiviral therapy may have reduced such longer term complications, due to the immune dysregulatory nature of this mutation. [ABSTRACT FROM AUTHOR]
Published: 2018
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332. Setting vaccination order: GUIDANCE ON BAME COMMUNITIES ‘TRIES TO SEPARATE SCIENCE FROM EMOTION’.

Author: TANG, JULIAN W.
Subjects: ORDERED sets, COMMUNITIES, EMOTIONS
Abstract: The article announces Prime minister Boris Johnson's government has set out guidelines for the vaccine roll-out.
Published: 2020

333. Deciphering the BEAST, Bayesian Evolutionary Analysis with BEAST by Alexei J Drummond and Remco R. Bouckaert. Cambridge University Press, Cambridge, UK. 260 pp. Hardback (available from Sep. 30 2015, USA; and 6 Aug. 2015, UK). ISBN-10: 1107019656. ISBN-13: 978-1107019652. $58.49 from www.amazon.com; £39.99 from www.amazon.co.uk

Author: Tang, Julian W.
Subjects: *BAYESIAN analysis, *EVOLUTIONARY theories, *DATA analysis
Published: 2016
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334. Influenza A and B Viruses in Fine Aerosols of Exhaled Breath Samples from Patients in Tropical Singapore.

Author: Chow, Vincent T. K., Tay, Douglas Jie Wen, Chen, Mark I. C., Tang, Julian W., Milton, Donald K., and Tham, Kwok Wai
Subjects: *INFLUENZA B virus, *AEROSOLS, *INFLUENZA viruses, *RNA viruses, *POLYMERASE chain reaction
Abstract: Influenza is a highly contagious respiratory illness that commonly causes outbreaks among human communities. Details about the exact nature of the droplets produced by human respiratory activities such as breathing, and their potential to carry and transmit influenza A and B viruses is still not fully understood. The objective of our study was to characterize and quantify influenza viral shedding in exhaled aerosols from natural patient breath, and to determine their viral infectivity among participants in a university cohort in tropical Singapore. Using the Gesundheit-II exhaled breath sampling apparatus, samples of exhaled breath of two aerosol size fractions ("coarse" > 5 µm and "fine" ≤ 5 µm) were collected and analyzed from 31 study participants, i.e., 24 with influenza A (including H1N1 and H3N2 subtypes) and 7 with influenza B (including Victoria and Yamagata lineages). Influenza viral copy number was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infectivity of influenza virus in the fine particle fraction was determined by culturing in Madin–Darby canine kidney cells. Exhaled influenza virus RNA generation rates ranged from 9 to 1.67 × 105 and 10 to 1.24 × 104 influenza virus RNA copies per minute for the fine and coarse aerosol fractions, respectively. Compared to the coarse aerosol fractions, influenza A and B viruses were detected more frequently in the fine aerosol fractions that harbored 12-fold higher viral loads. Culturable virus was recovered from the fine aerosol fractions from 9 of the 31 subjects (29%). These findings constitute additional evidence to reiterate the important role of fine aerosols in influenza transmission and provide a baseline range of influenza virus RNA generation rates. [ABSTRACT FROM AUTHOR]
Published: 2023
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335. Comparison of the IMDx Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus A/B Assay on the m2000 Platform with Real-Time Reverse Transcriptase PCR Assays

Author: Adachi, Dena, Tang, Julian W., Lundeberg, Roberta, Tipples, Graham, Charlton, Carmen L., and Drews, Steven J.
Published: 2014
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336. Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies.

Author: Zabidi, Nur Zawanah, Liew, Hern Liang, Farouk, Isra Ahmad, Puniyamurti, Ashwini, Yip, Ashley Jia Wen, Wijesinghe, Vindya Nilakshi, Low, Zheng Yao, Tang, Julian W., Chow, Vincent T. K., and Lal, Sunil K.
Subjects: *SARS-CoV-2, *SARS-CoV-2 Omicron variant, *SARS-CoV-2 Delta variant, *THERAPEUTICS, *VACCINATION
Abstract: The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks. [ABSTRACT FROM AUTHOR]
Published: 2023
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337. Discriminatory Ability of Gas Chromatography–Ion Mobility Spectrometry to Identify Patients Hospitalized With COVID-19 and Predict Prognosis.

Author: Nazareth, Joshua, Pan, Daniel, Kim, Jee Whang, Leach, Jack, Brosnan, James G, Ahmed, Adam, Brodrick, Emma, Bird, Paul, Wicaksono, Alfian, Daulton, Emma, Tang, Julian W, Williams, Caroline, Haldar, Pranabashis, Covington, James A, Pareek, Manish, and Sahota, Amandip
Subjects: *COVID-19, *CONTINUOUS positive airway pressure, *RECEIVER operating characteristic curves, *PROGNOSIS, *RESPIRATORY infections
Abstract: Background Rapid diagnostic and prognostic tests for coronavirus disease (COVID-19) are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography–ion mobility spectrometry (GC-IMS) in hospitalized patients with COVID-19. Methods Between February and May 2021, we took 1 breath sample for analysis using GC-IMS from participants who were admitted to the hospital for COVID-19, participants who were admitted to the hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, United Kingdom. Demographic, clinical, and radiological data, including requirement for continuous positive airway pressure (CPAP) ventilation as a marker for severe disease in the COVID-19 group, were collected. Results A total of 113 participants were recruited into the study. Seventy-two (64%) were diagnosed with COVID-19, 20 (18%) were diagnosed with another respiratory infection, and 21 (19%) were healthy controls. Differentiation between participants with COVID-19 and those with other respiratory tract infections with GC-IMS was highly accurate (sensitivity/specificity, 0.80/0.88; area under the receiver operating characteristics curve [AUROC], 0.85; 95% CI, 0.74–0.96). GC-IMS was also moderately accurate at identifying those who subsequently required CPAP (sensitivity/specificity, 0.62/0.80; AUROC, 0.70; 95% CI, 0.53–0.87). Conclusions GC-IMS shows promise as both a diagnostic tool and a predictor of prognosis in hospitalized patients with COVID-19 and should be assessed further in larger studies. [ABSTRACT FROM AUTHOR]
Published: 2022
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338. Performing under Pressure: Insights into the Diagnostic Testing Burden at a UK National Health Service Clinical Virology Laboratory during the SARS-CoV-2 Pandemic.

Author: Bird, Paul William, Taylor, Georgina, Cafferata, Jessica, Gardener, Judi, McMurray, Claire L., Fletcher, Oliver, Toovey, Oliver T. R., Holmes, Christopher W., and Tang, Julian W.
Subjects: *COVID-19, *DIAGNOSTIC virology, *COVID-19 pandemic, *PATHOLOGICAL laboratories, *DIAGNOSIS methods, *VIRUS diseases
Abstract: UK National Health Service (NHS) Clinical Virology Departments provide a repertoire of tests on clinical samples to detect the presence of viral genomic material or host immune responses to viral infection. In December 2019, a novel coronavirus (SARS-CoV-2) emerged which quickly developed into a global pandemic; NHS laboratories responded rapidly to upscale their testing capabilities. To date, there is little information on the impact of increased SARS-CoV-2 screening on non-SARS-CoV-2 testing within NHS laboratories. This report details the virology test requests received by the Leicester-based NHS Virology laboratory from January 2018 to May 2022. Data show that in spite of a dramatic increase in screening, along with multiple logistic and staffing issues, the Leicester Virology Department was mostly able to maintain the same level of service for non-respiratory virus testing while meeting the new increase in SARS-CoV-2 testing. [ABSTRACT FROM AUTHOR]
Published: 2022
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339. What were the historical reasons for the resistance to recognizing airborne transmission during the COVID‐19 pandemic?

Author: Jimenez, Jose L., Marr, Linsey C., Randall, Katherine, Ewing, Edward Thomas, Tufekci, Zeynep, Greenhalgh, Trish, Tellier, Raymond, Tang, Julian W., Li, Yuguo, Morawska, Lidia, Mesiano‐Crookston, Jonathan, Fisman, David, Hegarty, Orla, Dancer, Stephanie J., Bluyssen, Philomena M., Buonanno, Giorgio, Loomans, Marcel G. L. C., Bahnfleth, William P., Yao, Maosheng, and Sekhar, Chandra
Subjects: *AIRBORNE infection, *COVID-19 pandemic, *PANDEMICS, *PUBLIC health officers, *CHOLERA, *INFECTIOUS disease transmission, *GERM theory of disease, *RESPIRATORY diseases
Abstract: The question of whether SARS‐CoV‐2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID‐19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID‐19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases. [ABSTRACT FROM AUTHOR]
Published: 2022
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340. Detection of influenza A(H3N2) viruses with polymerase acidic subunit substitutions after and prior to baloxavir marboxil treatment during the 2022–2023 influenza season in Japan.

Author: Chon, Irina, Wagatsuma, Keita, Saito, Reiko, Tang, Julian W., Isamu, Sato, Suzuki, Eitaro, Shirahige, Yutaka, Kawashima, Takashi, Minato, Michiyoshi, Kodo, Naoki, Masaki, Hironori, Hamabata, Hirotsune, Yoshioka, Sayaka, Ichikawa, Yusuke, Sun, Yuyang, Li, Jiaming, Otoguto, Teruhime, and Watanabe, Hisami
Subjects: *SEASONAL influenza, *INFLUENZA viruses, *NUCLEOTIDE sequencing, *INFLUENZA, *NEURAMINIDASE
Abstract: Baloxavir marboxil (baloxavir), approved as an anti-influenza drug in Japan in March 2018, can induce reduced therapeutic effectiveness due to PA protein substitutions. We assessed PA substitutions in clinical samples from influenza-infected children and adults pre- and post-baloxavir treatment, examining their impact on fever and symptom duration. During the 2022–2023 influenza season, the predominant circulating influenza subtype detected by cycling-probe RT-PCR was A(H3N2) (n = 234), with a minor circulation of A(H1N1)pdm09 (n = 10). Of the 234 influenza A(H3N2) viruses collected prior to baloxavir treatment, 2 (0.8%) viruses carry PA/I38T substitution. One virus was collected from a toddler and one from an adult, indicating the presence of viruses with reduced susceptibility to baloxavir, without prior exposure to the drug. Of the 54 paired influenza A(H3N2) viruses collected following baloxavir treatment, 8 (14.8%) viruses carried E23 K/G, or I38 M/T substitutions in PA. Variant calling through next-generation sequencing (NGS) showed varying proportions (6–100 %), a polymorphism and a mixture of PA/E23 K/G, and I38 M/T substitutions in the clinical samples. These eight viruses were obtained from children aged 7–14 years, with a median fever duration of 16.7 h and a median symptom duration of 93.7 h, which were similar to those of the wild type. However, the delayed viral clearance associated with the emergence of PA substitutions was observed. No substitutions conferring resistance to neuraminidase inhibitors were detected in 37 paired samples collected before and following oseltamivir treatment. These findings underscore the need for ongoing antiviral surveillance, informing public health strategies and clinical antiviral recommendations for seasonal influenza. • Antiviral surveillance of influenza viruses circulated in Japan (2022–2023 season) was described. • Two viruses harboring PA/I38T (0.8%) prior to antiviral treatment were observed. • Eight viruses with PA variants (14.8%) appeared after baloxavir administration. • Duration of fever and symptoms between patients with and without PA variants after baloxavir treatment did not differ. • The delayed viral clearance associated with the emergence of PA substitutions was observed. [ABSTRACT FROM AUTHOR]
Published: 2024
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341. COVID-19 in Hong Kong – Public health, food safety, and animal vectors perspectives.

Author: Hon, K.L., Leung, K.K.Y, Tang, Julian W., Leung, Alexander K.C., and Li, Yuguo
Subjects: *COVID-19, *SARS-CoV-2, *FOOD safety, *PUBLIC health, *SARS virus, *PANDEMICS
Abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), has led to escalating morbidity and mortality in all nations and cities. SARS-CoV-2 lies within the same coronavirus family as SARS-CoV (2003) and MERS-CoV (2012), though there are genetic and epidemiological differences between the viruses, as well as different clinical presentations in the patients. Despite this, Hong Kong has so far managed to control the pandemic very successfully. Here we offer a Hong Kong perspective on different aspects of the pandemic virus (SARS-CoV-2) and the disease : public health (diagnosis and control), food safety (reducing transmission in the workplace) and animal vectors (controlling potential reservoirs of the virus and their movements). [ABSTRACT FROM AUTHOR]
Published: 2021
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342. Is the UK prepared for seasonal influenza in 2022-23 and beyond?

Author: Nazareth, Joshua, Pan, Daniel, Martin, Christopher A, Barr, Ian, Sullivan, Sheena G, Stephenson, Iain, Sahota, Amandip, Clark, Tristan W, Nellums, Laura B, Tang, Julian W, and Pareek, Manish
Published: 2022
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343. Can we use viral receptor mapping and particle deposition models to predict the clinical severity of novel airborne pathogens?

Author: Pillay, Kineshta, Marr, Linsey C., Henriques, Andre, Martin, Andrew R., Prussin, Aaron J., Aleixo, Luis, Andreini, Marco, Mounet, Nicolas, Finlay, Warren H., and Tang, Julian W.
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344. Concomitant, consecutive, self-obtained facemask and swab samples from exhaled breath, pox lesions, nasopharynx and the face in patients recovering from mpox – A longitudinal sampling study

Author: Pan, Daniel, Atkinson, Barry, Decker, Jonathan, Williams, Caroline M., Nazareth, Joshua, Martin, Christopher A., Bird, Paul, Fahad, Muhammad, Nicholls, Ian, Spencer, Antony, Onianwa, Okechukwu, Vogt, Alexander, Sahota, Amandip, Tang, Julian W., Stephenson, Iain, Bennett, Allan M., Pareek, Manish, and Barer, Michael R.
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345. Estimation of local transmissibility in the early phase of monkeypox epidemic in 2022.

Author: Kwok, Kin On, Wei, Wan In, Tang, Arthur, Wong, Samuel Yeung Shan, and Tang, Julian W.
Subjects: *MONKEYPOX, *SMALLPOX vaccines, *POISSON processes, *BRANCHING processes
Abstract: To estimate the basic reproductive number (Ro) to help us understand and control the spread of monkeypox in immunologically naive populations. Using three highest incidence populations including England, Portugal, and Spain as examples as of 18 June 2022, we employed the branching process with a Poisson likelihood and gamma-distributed serial interval to fit daily reported case data of monkeypox to estimate Ro. Sensitivity analyses were performed by varying mean serial interval from 6.8 to 12.8 days. The median posterior estimates of Ro for monkeypox in the three study populations were statistically >1 (England: Ro = 1.60 [95% (credible interval) CrI, 1.50–1.70]; Portugal: Ro = 1.40 [95% CrI, 1.20–1.60]; Spain: Ro = 1.80 [95% CrI, 1.70–2.00]). Ro estimates varied over 1.30 to 2.10, depending on the serial interval. The updated Ro estimates across different populations will inform policy makers' plans for public health control measures. Currently, monkeypox has a sustainable outbreak potential and may challenge healthcare systems, mainly due to declines in the population level immunity to Orthopoxviruses since the cessation of routine smallpox vaccination. Smallpox vaccination has been shown to be effective in protecting (≤85% effectiveness) against monkeypox infection in earlier times. So early postexposure vaccination is currently being offered in an attempt to control its spread. [ABSTRACT FROM AUTHOR]
Published: 2022
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346. The need for a sequencing-based assay to supplement the Abbott m2000 RealTime HCV Genotype II assay: A 1 year analysis.

Author: Benedet, Marlin, Adachi, Dena, Wong, Anita, Wong, Sallene, Pabbaraju, Kanti, Tellier, Raymond, and Tang, Julian W.
Subjects: *BIOLOGICAL assay, *HEPATITIS C treatment, *VIRAL genetics, *VIRUS research, *MICROBIOLOGY
Abstract: Highlights: [•] The Abbott m2000 HCV genotyping II assay resolves over 90% of the HCV genotypes (G). [•] Out of 1052 samples tested, 89 (8.5%) required further sequencing. [•] Of these 89, 54 G1 samples were mostly sub-genotyped as 1a, with some 6, 1b and 1c. [•] Of these 89, 16 ‘indeterminate’ samples were mostly G2s and G3s. [•] Of these 89, 12 ‘mixed’ samples were mostly one of the genotypes from the mixture. [Copyright &y& Elsevier]
Published: 2014
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347. Full-Genome Analysis of Avian Influenza A(H5N1) Virus from a Human, North America, 2013.

Author: Pabbaraju, Kanti, Tellier, Raymond, Wong, Sallene, Yan Li, Bastien, Nathalie, Tang, Julian W., Drews, Steven J., Yunho Jang, Davis, C. Todd, Fonseca, Kevin, and Tipples, Graham A.
Subjects: *GENOMICS, *PATHOGENIC microorganisms, *AVIAN influenza, *HEMAGGLUTININ, *POLYMERASE chain reaction, *NEURAMINIDASE
Abstract: Full-genome analysis was conducted on the first isolate of a highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found. [ABSTRACT FROM AUTHOR]
Published: 2014
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348. Comparison of Pandemic (H1N1) 2009 and Seasonal Influenza Viral Loads, Singapore.

Author: Lee, Chun K., Lee, Hong K., Loh, Tze P., Lai, Florence Y. L., Tambyah, Paul A., Chiu, Lily, Koay, Evelyn S. C., and Tang, Julian W.
Subjects: *H1N1 influenza, *PANDEMICS, *INFLUENZA, *SYMPTOMS, *VIRAL load, *VIRUS diseases, *PATIENTS
Abstract: Mean viral loads for patients with pandemic (H1N1) 2009 were ≈1 log10 times lower than those for patients with seasonal influenza within the first week after symptom onset. Neither pandemic nor seasonal influenza viral loads correlated with clinical severity of illness. No correlation was found between viral loads and concurrent illness. [ABSTRACT FROM AUTHOR]
Published: 2011
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349. Viral etiology of acute exacerbations of COPD in Hong Kong.

Author: Ko FW, Ip M, Chan PK, Chan MC, To KW, Ng SS, Chau SS, Tang JW, Hui DS, Ko, Fanny W S, Ip, Margaret, Chan, Paul K S, Chan, Michael C H, To, Kin-Wang, Ng, Susanna S S, Chau, Shirley S L, Tang, Julian W, and Hui, David S C
Abstract: Introduction: Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD). However, little is known about viral etiology related to AECOPD in Asia. We aimed to study the viral etiology of AECOPD in Hong Kong.Methods: Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture. Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge.Results: There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 +/- 7.7 years [+/- SD]; 160 men). Mean FEV(1) was 39.6 +/- 18.9% of predicted normal, and FEV(1)/FVC ratio was 58.0 +/- 15.2%. Fifty-eight episodes (22.1%) yielded positive viral PCR results. The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%). The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture. The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV(1) >or= 50%, >or= 30 to 50%, and < 30% of predicted normal. Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 yearConclusion: Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong. These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD. [ABSTRACT FROM AUTHOR]
Published: 2007

350. Chikungunya Fever, Hong Kong.

Author: Lee, Nelson, Wong, Chun K., Lam, Wai Y., Wong, Ann, Lim, Wilina, Lam, Christopher W. K., Cockram, Clive S., Sung, Joseph J. Y., Chan, Paul K. S., and Tang, Julian W.
Subjects: *LETTERS to the editor, *FEVER
Abstract: The article presents a letter to the editor in response to the article "Chikungunya Fever, Hong Kong," by Nelson Lee et al, which appeared in a 2006 issue.
Published: 2006
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