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

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

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

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS o

Thromboprophylaxis and mortality among patients who developed venous thromboembolism in seven major hospitals in Saudi Arabia

Introduction: Venous thromboembolism (VTE) during hospitalization is a serious and potentially fatal condition. Despite its effectiveness, evidence-based thromboprophylaxis is still underutilized in many countries including Saudi Arabia. Objective of the Study: Our objectives were to determine how often hospital-acquired VTE patients received appropriate thromboprophylaxis, VTE-associated mortality, and the percentage of patients given anticoagulant therapy and adherence to it after discharged. Methods: This study was conducted in seven major hospitals in Saudi Arabia. From July 1, 2009, till June 30, 2010, all recorded deep vein thrombosis (DVT) and pulmonary embolism (PE) cases were noted. Only patients with confirmed VTE diagnosis were included in the analysis. Results: A total of 1241 confirmed VTE cases occurred during the 12-month period. Most (58.3%) of them were DVT only, 21.7% were PE, and 20% were both DVT and PE. 21.4% and 78.6% of confirmed VTE occurred in surgical and medical patients, respectively. Only 40.9% of VTE cases received appropriate prophylaxis (63.2% for surgical patients and 34.8% for medical patients; P 0.05). Appropriate thromboprophylaxis was associated with 4.11% absolute risk reduction in mortality (95% confidence interval: 0.24%–7.97%). Most (89.4%) of the survived patients received anticoagulation therapy at discharge and 71.7% of them were adherent to it on follow-up. Conclusion: Thromboprophylaxis was underutilized in major Saudi hospitals denoting a gap between guideline and practice. This gap was more marked in medical than surgical patients. Hospital-acquired VTE was associated with significant mortality. Efforts to improve thromboprophylaxis utilization are warranted

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

Background: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their eff ectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. Methods: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confi rmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identifi ed potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. Findings: We included data for 29 234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0.81; 95% CI 0.70-0.93; p=0.0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0.48; 95% CI 0.41-0.56; p<0.0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0.50; 95% CI 0.37-0.67; p<0.0001). These associations with reduced mortality risk were less pronounced and not signifi cant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1.23] [95% CI 1.18-1.28]; p<0.0001 for the increasing HR with each day's delay). Interpretation We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection

Neuraminidase inhibitors and hospital length of stay: a meta-analysis of individual participant data to determine treatment effectiveness among patients hospitalized with nonfatal 2009 pandemic iInfluenza A(H1N1) virus infection

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

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

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of &lt;1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated &lt;2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment

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

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\ub70%) had IRP; conversely, 3349 (16\ub72%) 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\ub783 (95% CI 0\ub764-1\ub706; P = 0\ub7136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0\ub772 (0\ub744-1\ub717; P = 0\ub7180)] or likelihood of requiring ventilatory support [adj. OR = 1\ub717 (0\ub771-1\ub792; P = 0\ub7537)], but early treatment versus later significantly reduced mortality [adj. OR = 0\ub770 (0\ub755-0\ub788; P = 0\ub7003)] and likelihood of requiring ventilatory support [adj. OR = 0\ub768 (0\ub754-0\ub785; P = 0\ub7001)]. 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

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.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p&lt;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&lt;0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p&lt;0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche