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

Mortalidad atribuible a gripe en los períodos prevacunación y posvacunación en Argentina: estudio ecológico (2002-2016)

Objetivos. Comparar las tasas de mortalidad por infección respiratoria aguda grave atribuible a gripe (IRAG) entre los períodos antes de la vacunación (AV) y después de la vacunación (DV), conocer la evolución histórica y estacionalidad de serie histórica entre 2002-2016 y estimar el riesgo de morir de niños entre 6 y 23 meses mediante el empleo de un modelo estadístico. Métodos. Estudio de serie histórica con datos oficiales de mortalidad del informe estadístico de defunción. Se consideraron como IRAG los códigos de CIE-10 entre J09-18.9 y J22X. Se calcularon tasas brutas (TB) y ajustadas por edad (TAE) y se compararon los períodos AV (2002-2009) y DV (2010-2016) con prueba de χ2. El mejor modelo estadístico fue el que comparó las defunciones por IRAG en niños durante el 2002 con otros años. Se analizaron los datos con programa R, nivel de significancia P <0,05. Resultados. El 4,6% (301 747) de las defunciones fueron por IRAG, con una edad mediana de 82 años, el porcentaje de fallecidos menores de dos años disminuyó en el período DV (2,34% a 0,99%, P < 0,05). Se presentó una marcada estacionalidad en invierno. Las TAE en gerontes pasaron de 259,8 AV a 328,6 por 100 000 personas DV (P < 0,05). En los niños, la TB disminuyó de manera significativa, estimando que el riesgo de morir por IRAG, comparado con el año 2 002, fue significativamente menor durante 3 años DV. Conclusiones. La disminución de la mortalidad por gripe en Argentina fue más evidente en niños, con un descenso estimado de 3,5 niños fallecidos por IRAG por mes

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