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.

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

Short-term enteral supplementation of non-human neutral and acidic oligosaccharides during the neonatal period in preterm infants does not decrease the incidence of allergic and infectious diseases during the first year of life.

Objective: To compare feeding tolerance, nutrient intake and growth in preterm infants (p32 weeks, p1750 g) fed either a standard nonhydrolyzed whey-casein (nHWC) or a partially hydrolyzed whey (pHW) preterm infant formula.Study Design: In this double-blind randomized controlled trial infants were fed either formula for at least 3 weeks. Intake was monitored daily, serum chemistries and growth weekly. Data were analyzed using analysis of covariance.Result: A total of 80 infants were enrolled, 72 completed the study. No differences were noted in demographic characteristics. No differences were detected in feeding tolerance, intakes (118 ± 21 vs 119 ± 14; nHWC vs pHW) or growth weight, 28 ± 1.5 vs 28 ± 1.6 g per day; length, 1.0 ± 0.7 vs 1.0±0.6 cm per week; head circumference, 0.9±0.4 vs 1.0±0.44 cm per week). At the end of study, blood urea nitrogen (5.2 ± 3.1 <6.7±2.3 mg per 100 ml, nHWC4.4 ± 0.5 g per 100 ml) and albumin (2.7 ± 0.3 >2.6 ± 0.4 g per 100 ml) differed. Conclusion:A pHW preterm infant formula was not associated with improved feeding tolerance, enteral intake or growth but differences in serum chemistries. These are unlikely to be clinically relevant because values were well within normal limits for preterm infants, whereas growth was identical in both groups and paralleled that 'in utero'.