International audienceSummaryBackground Neuraminidase inhibitors were widely used during the 2009–10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. Methods We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. Findings We included data for 29 234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70–0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41–0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37–0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18–1·28]; p<0·0001 for the increasing HR with each day's delay). Interpretation We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. Funding F Hoffmann-La Roche

BackgroundThe 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.MethodsA 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.ResultsOf 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)].ConclusionsEarly 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.

Patients on extracorporeal membrane oxygenation (ECMO) frequently requires continuous renal replacement therapy (CRRT). Additional anticoagulation for the CRRT circuit is usually not employed, but this may increases the risk of clot embolization, which shortens oxygenator lifespan and increases patient's risk. We report our experience on the use of regional citrate anticoagulation continuous venovenous hemofiltration (RCA-CVVH) connected to an ECMO circuit, which could be useful during low heparin or heparin-free ECMO situations. Regional citrate anticoagulation continuous venovenous hemofiltration was performed using AK200US machine with a blood flow of 150 ml/min, Acid Citrate Dextrose Solution prefilter infusion at 240 ml/hr, ultrafiltration rate of 2,040 ml/hr, and postdilutional online generated replacement fluid infused as appropriate. The circuit was aimed to run for 30 hrs. From May 2009 to May 2013, 63 patients received ECMO and 29 received RCA-CVVH. The median total CVVH time was 131 hrs (interquartile range [IQR]: 61-224 hrs), and hemofilter life was 27.2 hrs (IQR: 25.7-28.5 hrs). No hemofilter or oxygenator was changed because of clotting. Their hospital mortality was 27.6%. There were eight patients, who were judged to be too sick for anticoagulation, received predilution CRRT during the same period. Their hospital mortality was 75%. In conclusion, online postdilutional RCA-CVVH connected to an ECMO circuit is a feasible, safe, and effective CRRT technique.

pNGAL correlated with severity of AKI and requirement of renal replacement therapy in ICU patients who received major or ultra-major non-cardiac surgery. However, the benefit of adding pNGAL into clinical AKI prediction model is marginal.

Background Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods A multi-center prospective study carried out in 2 tertiary referral center ICUs in Hong Kong with serum citrate levels measured at baseline, 2-, 6-, 12-, 24-, 36-, 48- and 72-hours after initiation of RCA CRRT and their relationships with development of CA examined. Results Amongst the 133 patients analyzed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline, 2-, 6- and 12-hours after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P &lt; 0.001, for all). The CA group also had higher serum citrate levels than the non-CA group [median (IQR): 0.93(0.81–1.16) mmol/L vs. 0.37(0.26–0.57) mmol/L, P &lt; 0.001]. Using a cut-off of 0.85 mmol/L, serum citrate level had a sensitivity (SN) of 0.77 and a specificity (SP) 0.96 for the diagnosis of CA (AUROC 0.90, P &lt; 0.001). The 2-hr and 6-hr serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-hr and 6-hr citrate levels using cut-off values of 0.34 and 0.63 mmol/L respectively; P &lt; 0.001). Conclusion Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.