Quality of life of survivors of paediatric intensive care

Objective: The mortality rate in paediatric intensive care units (PICU) has fallen over the last two decades. More advanced treatment is offered to children with life-threatening disease and there is substantial interest in knowing whether long term outcome and quality of life after intensive care are acceptable

Early high flow nasal cannula therapy in bronchiolitis, a prospective randomised control trial (protocol): A Paediatric Acute Respiratory Intervention Study (PARIS)

Background Bronchiolitis imposes the largest health care burden on non-elective paediatric hospital admissions worldwide, with up to 15 % of cases requiring admission to intensive care. A number of previous studies have failed to show benefit of pharmaceutical treatment in respect to length of stay, reduction in PICU admission rates or intubation frequency. The early use of non-invasive respiratory support devices in less intensive scenarios to facilitate earlier respiratory support may have an impact on outcome by avoiding progression of the disease process. High Flow Nasal Cannula (HFNC) therapy has emerged as a new method to provide humidified air flow to deliver a non-invasive form of positive pressure support with titratable oxygen fraction. There is a lack of high-grade evidence on use of HFNC therapy in bronchiolitis. Methods/Design Prospective multi-centre randomised trial comparing standard treatment (standard subnasal oxygen) and High Flow Nasal Cannula therapy in infants with bronchiolitis admitted to 17 hospitals emergency departments and wards in Australia and New Zealand, including 12 non-tertiary regional/metropolitan and 5 tertiary centres. The primary outcome is treatment failure; defined as meeting three out of four pre-specified failure criteria requiring escalation of treatment or higher level of care; i) heart rate remains unchanged or increased compared to admission/enrolment observations, ii) respiratory rate remains unchanged or increased compared to admission/enrolment observations, iii) oxygen requirement in HFNC therapy arm exceeds FiO2 ≥ 40 % to maintain SpO2 ≥ 92 % (or ≥94 %) or oxygen requirement in standard subnasal oxygen therapy arm exceeds >2L/min to maintain SpO2 ≥ 92 % (or ≥94 %), and iv) hospital internal Early Warning Tool calls for medical review and escalation of care. Secondary outcomes include transfer to tertiary institution, admission to intensive care, length of stay, length of oxygen treatment, need for non-invasive/invasive ventilation, intubation, adverse events, and cost. Discussion This large multicenter randomised trial will allow the definitive assessment of the efficacy of HFNC therapy as compared to standard subnasal oxygen in the treatment of bronchiolitis

Impact of depth of propofol anaesthesia on functional residual capacity and ventilation distribution in healthy preschool children

Background Propofol is commonly used in children undergoing diagnostic interventions under anaesthesia or deep sedation. Because hypoxaemia is the most common cause of critical deterioration during anaesthesia and sedation, improved understanding of the effects of anaesthetics on pulmonary function is essential. The aim of this study was to determine the effect of different levels of propofol anaesthesia on functional residual capacity (FRC) and ventilation distribution. Methods In 20 children without cardiopulmonary disease mean age (sd) 49.75 (13.3) months and mean weight (sd) 17.5 (3.9)kg, anaesthesia was induced by a bolus of i.v. propofol 2mgkg−1 followed by an infusion of propofol 120µgkg−1min−1 (level I). Then, a bolus of propofol 1mgkg−1 was given followed by a propofol infusion at 240µgkg−1min−1 (level II). FRC and lung clearance index (LCI) were calculated at each level of anaesthesia using multibreath analysis. Results The FRC mean (sd) decreased from 20.7 (3.3)mlkg−1 at anaesthesia level I to 17.7 (3.9)mlkg−1 at level II (P < 0.0001). At the same time, mean (sd) LCI increased from 10.4 (1.1) to 11.9 (2.2) (P = 0.0038), whereas bispectral index score values decreased from mean (sd) 57.5 (7.2) to 35.5 (5.9) (P < 0.0001). Conclusions Propofol elicited a deeper level of anaesthesia that led to a significant decrease of the FRC whereas at the same time the LCI, an index for ventilation distribution, increased indicating an increased vulnerability to hypoxaemi

Incidence, management, and outcomes of cardiovascular insufficiency in critically ill term and late preterm newborn infants

OBJECTIVE: The objective of this study was to characterize the incidence, management, and short-term outcomes of cardiovascular insufficiency (CVI) in mechanically ventilated newborns, evaluating four separate prespecified definitions. STUDY DESIGN: Multicenter, prospective cohort study of infants ≥34 weeks gestational age (GA) and on mechanical ventilation during the first 72 hours. CVI was prospectively defined as either (1) mean arterial pressure (MAP) < GA; (2) MAP < GA + signs of inadequate perfusion; (3) any therapy for CVI; or (4) inotropic therapy. Short-term outcomes included death, days on ventilation, oxygen, and to full feedings and discharge. RESULTS: Of 647 who met inclusion criteria, 419 (65%) met ≥1 definition of CVI. Of these, 98% received fluid boluses, 36% inotropes, and 17% corticosteroids. Of treated infants, 46% did not have CVI as defined by a MAP < GA ± signs of inadequate perfusion. Inotropic therapy was associated with increased mortality (11.1 vs. 1.3%; p < 0.05). CONCLUSION: More than half of the infants met at least one definition of CVI. However, almost half of the treated infants met none of the definitions. Inotropic therapy was associated with increased mortality. These findings can help guide the design of future studies of CVI in newborn

Burden of disease and change in practice in Critically Ill Infants with Bronchiolitis

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs)

A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis

BACKGROUND: High-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. RESULTS: The analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high-flow group, as compared with 23% (167 of 733) in the standard-therapy group (risk difference, −11 percentage points; 95% confidence interval, −15 to −7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard-therapy group who had treatment failure, 102 (61%) had a response to high-flow rescue therapy. CONCLUSIONS: Among infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. (Funded by the National Health and Medical Research Council and others; Australian and New Zealand Clinical Trials Registry number, ACTRN12613000388718.

Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network.

OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at CONCLUSION: Although the majority of infants with GAs of \u3eor=24 weeks survive, high rates of morbidity among survivors continue to be observed

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants

Background: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants 99% versus 99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P = 0.007). Conclusions: Early dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC