Identifying effect modifiers of systemic hydrocortisone treatment initiated 7-14 days after birth in ventilated very preterm infants on long-term outcome: secondary analysis of a randomised controlled trial.

OBJECTIVE: To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA). DESIGN: Secondary analysis of a randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life. INTERVENTION: Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: The composite of death or neurodevelopmental impairment (NDI) at 2 years' CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots. RESULTS: The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); ≥27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); ≥27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups. CONCLUSION: This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by its component death. There was insufficient evidence for other selected candidate effect modifiers.

The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.

OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

Effect of systemic hydrocortisone in ventilated preterm infants on parent-reported behavioural outcomes at 2 years' corrected age: follow-up of a randomised clinical trial.

OBJECTIVE: To report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years' corrected age (CA). DESIGN: Randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. INTERVENTION: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: Parent-reported behavioural outcomes at 2 years' CA assessed with the Child Behavior Checklist (CBCL 1½-5). RESULTS: Parents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalising and externalising problems, respectively; these scores were not significantly different between groups (mean difference -1.52 (95% CI -4.00 to 0.96), -2.40 (95% CI -4.99 to 0.20) and -0.81 (95% CI -3.40 to 1.77), respectively). In the subscales, we found a significantly lower T-score for anxiety problems in the hydrocortisone group (mean difference -1.26, 95% CI -2.41 to -0.12). CONCLUSION: This study found high rates of behaviour problems at 2 years' CA following very preterm birth, but these problems were not associated with hydrocortisone treatment initiated between 7 and 14 days after birth in ventilated preterm infants. TRIAL REGISTRATION NUMBER: NTR2768; EudraCT 2010-023777-19.

Short-term pulmonary and systemic effects of hydrocortisone initiated 7-14 days after birth in ventilated very preterm infants: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week. DESIGN: Randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. INTERVENTION: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models. RESULTS: Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH2O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure. CONCLUSIONS: Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR2768; https://www.trialregister.nl/trial/2640) and European Union Clinical Trials Register (EudraCT, 2010-023777-19).

Importance of the pyrolysis for microstructure and superconducting properties of CSD-grown GdBa2Cu3O7-x-HfO2 nanocomposite films by the ex-situ approach.

For the first time, GdBa2Cu3O7-x nanocomposites were prepared by chemical solution deposition following the ex-situ approach. In particular, ~ 220 nm GdBa2Cu3O7-x-HfO2 (GdBCO-HfO2) nanocomposite films were fabricated starting from a colloidal solution of 5 mol% HfO2 nanoparticles. Hereby, one of the main challenges is to avoid the accumulation of the nanoparticles at the substrate interface during the pyrolysis, which would later prevent the epitaxial nucleation of the GdBCO grains. Therefore, the effect of pyrolysis processing parameters such as heating ramp and temperature on the homogeneity of the nanoparticle distribution has been investigated. By increasing the heating ramp to 300 °C/h and decreasing the final temperature to 300 °C, a more homogenous nanoparticle distribution was achieved. This translates into improved superconducting properties of the grown films reaching critical temperatures (Tc) of 94.5 K and self-field critical current densities ([Formula: see text]) at 77 K of 2.1 MA/cm2 with respect to films pyrolyzed at higher temperatures or lower heating ramps.

Neurodevelopmental outcomes of very preterm and very-low-birthweight infants in a population-based clinical cohort with a definite perinatal treatment policy.

BACKGROUND: With constant changes in neonatal care practices, recent information is valuable for healthcare providers and for parental counselling. The aim of the study was to describe the neurodevelopmental outcome in a cohort of very preterm (VPT)/very-low-birthweight (VLBW) infants at 2 years corrected age (CA). MATERIAL AND METHODS: This is a population-based cohort study of all infants born with a GA <31 weeks and/or BW < 1500 g between 2014 and 2016 admitted to the Flemish (Belgium) neonatal intensive care units. Infants had routine clinical follow-up around 2 years CA. The diagnosis of cerebral palsy (CP), visual and hearing impairments were recorded. Motor, cognitive and language outcomes were assessed using the Bayley-III. Neurodevelopmental impairment (NDI) was classified as mild (<1 standard deviation [SD]) or moderate-severe (<2SD) based on the defined categories of motor, cognitive, hearing, and vision impairments. RESULTS: Of the 1941 admissions, 92% survived to discharge and follow-up data were available for 1089 infants (61.1%). Overall, 19.3%, 18.9% and 41.8% of infants had a motor, cognitive and language delay, respectively. CP was diagnosed in 4.3% of the infants. Mild and moderate-to-severe NDI was observed in 25.2% and 10.9% of the infants, respectively. The number of infants with a normal outcome increased from nearly 40% in the category of GA<26 weeks to 70% for infants in the category of 30─31 weeks GA. CONCLUSION: At 2 years CA, 64% were free from NDI and 90% were free from moderate-to-severe NDI. However, a lower GA and BW are associated with higher rates of adverse neurodevelopmental outcomes at 2 years CA.

Monometallic Cerium Layered Double Hydroxide Supported Pd-Ni Nanoparticles as High Performance Catalysts for Lignin Hydrogenolysis.

Monometallic cerium layered double hydroxides (Ce-LDH) supports were successfully synthesized by a homogeneous alkalization route driven by hexamethylenetetramine (HMT). The formation of the Ce-LDH was confirmed and its structural and compositional properties studied by XRD, SEM, XPS, iodometric analyses and TGA. HT-XRD, N2-sorption and XRF analyses revealed that by increasing the calcination temperature from 200 to 800 °C, the Ce-LDH material transforms to ceria (CeO2) in four distinct phases, i.e., the loss of intramolecular water, dehydroxylation, removal of nitrate groups and removal of sulfate groups. When loaded with 2.5 wt% palladium (Pd) and 2.5 wt% nickel (Ni) and calcined at 500 °C, the PdNi-Ce-LDH-derived catalysts strongly outperform the PdNi-CeO2 benchmark catalyst in terms of conversion as well as selectivity for the hydrogenolysis of benzyl phenyl ether (BPE), a model compound for the α-O-4 ether linkage in lignin. The PdNi-Ce-LDH catalysts showed full selectivity towards phenol and toluene while the PdNi-CeO2 catalysts showed additional oxidation of toluene to benzoic acid. The highest BPE conversion was observed with the PdNi-Ce-LDH catalyst calcined at 600 °C, which could be related to an optimum in morphological and compositional characteristics of the support.

Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking. Objective: To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants. Design, Setting, and Participants: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017. Interventions: Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190). Main Outcomes and Measures: The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age. Results: Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%). Conclusions and Relevance: Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication. Trial Registration: Netherlands National Trial Register Identifier: NTR2768.

The Influence of Deposition Methods of Support Layer on Cordierite Substrate on the Characteristics of a MnO2-NiO-Co3O4/Ce0.2Zr0.8O2/Cordierite Three Way Catalyst.

This paper compares different coating methods (in situ solid combustion, hybrid deposition, secondary growth on seed, suspension, double deposition of wet impregnation and suspension) to deposit Ce0.2Zr0.8O2 mixed oxides on cordierite substrates, for use as a three way catalyst. Among them, the double deposition was proven to be the most efficient one. The coated sample shows a BET (Brunauer-Emmett-Teller) surface area of 25 m²/g, combined with a dense and crack free surface. The catalyst with a layer of MnO2-NiO-Co3O4 mixed oxides on top of the Ce0.2Zr0.8O2/cordierite substrate prepared by this method exhibits good activity for the treatment of CO, NO and C3H6 in exhaust gases (CO conversion of 100% at 250 °C, C3H6 conversion of 100% at 400 °C and NO conversion of 40% at 400 °C).

Effects of Varied Cleaning Methods on Ni-5% W Substrate for Dip-Coating of Water-based Buffer Layers: An X-ray Photoelectron Spectroscopy Study.

This work describes various combinations of cleaning methods involved in the preparation of Ni-5% W substrates for the deposition of buffer layers using water-based solvents. The substrate has been studied for its surface properties using X-ray photoelectron spectroscopy (XPS). The contaminants in the substrates have been quantified and the appropriate cleaning method was chosen in terms of contaminants level and showing good surface crystallinity to further consider them for depositing chemical solution-based buffer layers for Y1Ba2Cu3Oy (YBCO) coated conductors.

X-ray Photoelectron Spectroscopy (XPS) Depth Profiling for Evaluation of La2Zr2O7 Buffer Layer Capacity.

Lanthanum zirconate (LZO) films from water-based precursors were deposited on Ni-5%W tape by chemical solution deposition. The buffer capacity of these layers includes the prevention of Ni oxidation of the substrate and Ni penetration towards the YBCO film which is detrimental for the superconducting properties. X-ray Photoelectron Spectroscopy depth profiling was used to study the barrier efficiency before and after an additional oxygen annealing step, which simulates the thermal treatment for YBCO thin film synthesis. Measurements revealed that the thermal treatment in presence of oxygen could severely increase Ni diffusion. Nonetheless it was shown that from the water-based precursors' buffer layers with sufficient barrier capacity towards Ni penetration could be synthesized if the layers meet a certain critical thickness and density.

Virus removal by biogenic cerium.

The rare earth element cerium has been known to exert antifungal and antibacterial properties in the oxidation states +III and +IV. This study reports on an innovative strategy for virus removal in drinking water by the combination of Ce(III) on a bacterial carrier matrix. The biogenic cerium (bio-Ce) was produced by addition of aqueous Ce(III) to actively growing cultures of either freshwater manganese-oxidizing bacteria (MOB) Leptothrix discophora or Pseudomonas putida MnB29. X-ray absorption spectroscopy results indicated that Ce remained in its trivalent state on the bacterial surface. The spectra were consistent with Ce(III) ions associated with the phosphoryl groups of the bacterial cell wall. In disinfection assays using a bacteriophage as model, it was demonstrated that bio-Ce exhibited antiviral properties. A 4.4 log decrease of the phage was observed after 2 h of contact with 50 mg L(-1) bio-Ce. Given the fact that virus removal with 50 mg L(-1) Ce(III) as CeNO(3) was lower, the presence of the bacterial carrier matrix in bio-Ce significantly enhanced virus removal.

Ultra stable ordered mesoporous phenol/formaldehyde polymers as a heterogeneous support for vanadium oxide.

Ordered mesoporous phenol/formaldehyde polymers are presented as an ultra stable heterogeneous support for vanadium oxide.

Outcome at 3 years of age in a population-based cohort of extremely preterm infants.

OBJECTIVE: To assess health and neurodevelopmental outcome at 3 years of age in neonatal intensive care unit (NICU)-surviving children who were born at 26 or fewer weeks of gestation in a geographically defined region of Belgium from 1999 through 2000. METHODS: The study included a clinical examination and a standardized neurologic and developmental assessment. Disabilities were defined by international criteria. In 97% (92 of 95) of the children, accurate information on the presence of overall disability could be collected. RESULTS: Thirty-six percent (95% confidence interval [CI] 25-47%) of the formally assessed children (28 of 77) had deficient neuromotor development, with 5% of them showing severe sensory-communicative impairment. Mean (+/-standard deviation) scores on the Mental Developmental Index and Psychomotor Developmental Index were 81.2 (18.8) and 73.2 (17.8), respectively. Seventy percent (95% CI 60-80%) had a mental (Mental Developmental Index) or psychomotor (Psychomotor Developmental Index) impairment or both, assessed to be more than 1 standard deviation below the population mean. Mental and psychomotor outcome did not differ significantly when compared according to either gestational age, gender, or multiple birth (all P>.05). When either minor central dysfunction or cerebral palsy was not taken into account, normal mental development was recorded in 62% of the subjects. The cumulative of poor outcome (ie, disability- or prematurity-related death) among the 95 infants discharged alive was estimated to be 58% (95% CI 48-68%), representing 25 (26%) mildly-to-moderately disabled and 28 (29%) severely disabled toddlers, including two infants whose postdischarge deaths were directly related to prematurity. CONCLUSION: The average developmental outcome is poor in children born as extremely preterm infants. Finding early predictors of adverse outcome is a major challenge.

Conservative treatment for patent ductus arteriosus in the preterm.

BACKGROUND: A patent ductus arteriosus (PDA) is common among preterms, and prophylactic medical treatment has been advocated as the first-line approach. Conservative treatment may result in similar outcome, but without exposure to the harmful side effects of medication. A retrospective analysis revealed a ductal closure rate of 94% after conservative treatment with adjustment of ventilation (lowering the inspiratory time and increasing positive end expiratory pressure) and fluid restriction. OBJECTIVE: To study prospectively over one year the rate of PDA closure, and morbidity and mortality following conservative treatment. METHOD: Prospective study (1 January 2005 - 31 December 2005) including 30 newborns

A comparison of the pharmacokinetics of two dosing regimens of cisapride and their effects on corrected QT interval in premature infants.

OBJECTIVE: To compare the pharmacokinetics of two dosing regimens of cisapride and their effects on QT(c) interval. DESIGN: Thirty-one pre-term infants were enrolled in two neonatal intensive care units. In 16 infants, cisapride was started at 0.2 mg/kg orally every 6 h (group A) and in 15 infants at 0.1 mg/kg orally every 3 h (group B). Electrocardiograms were performed before and after 72 h of treatment to calculate the QT(c) interval according to the Bazett formula. After 72 h of treatment, cisapride and norcisapride trough concentrations, and concentrations 1 h after the next cisapride administration were quantified in serum. A linear regression analysis was performed to analyse the effect of postnatal and postconception age. RESULTS: At the start of cisapride treatment, mean postnatal age was 22.9+/-13.9 days (mean+/-SD) for group A and 23.3+/-15.0 days for group B, and mean postconception age was 34.0+/-1.8 weeks for group A and 33.3+/-0.8 weeks for group B. The QT(c) interval increased equally in both groups (group A: +37+/-20 ms, and group B: + 38+/-25 ms; P=0.9). Mean concentration of cisapride 1 h after administration was, as expected from the dosing regimen, significantly higher in group A than in group B (123.7+/-43.2 ng/ml versus 86.7+/-27.8 ng/ml; P=0.03).The difference in trough concentration was not significant (107.4+/-44.3 ng/ml versus 78.2+/-35.4 ng/ml; P=0.09). There was a positive correlation between QT(c) prolongation and cisapride serum concentration (peak: R(2)=0.20, P=0.015; trough: R(2)=0.24, P=0.008) and an inverse correlation between postnatal age and concentration 1 h after administration concentration of cisapride (R(2)=0.19, P=0.02). No correlation was found for postconception age. CONCLUSION: Postnatal age has an inverse relationship with cisapride serum concentration in premature infants, whereas postconception age is not correlated. The maturation process of the biotransformation system of cisapride during the first weeks of life, triggered by birth, but independent of gestational age at birth can explain this observation. The effect of cisapride on cardiac repolarisation is positively related with the cisapride serum concentration. Administering cisapride every 3 h instead of every 6 h could be advantageous, as it is associated with lower peak cisapride serum concentrations. Further investigations are required to confirm this and its potential clinical benefit on QT(c )and arrhythmia risk.