A Multicenter, Randomised Open Study of Early Corticosteroid Treatment (OSECT) in Preterm Infants With Respiratory Illness: Comparison of Early and Late Treatment and of Dexamethasone and Inhaled Budesonide

AIM: To compare early (15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease. METHODS: Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age 30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily. RESULTS: There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance. CONCLUSIONS: Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective

Making doors open: caring for families of children with severe cerebral palsy

Cerebral palsy is a relatively rare condition affecting approximately 2-2.5 children in every 1,000 (Parkes et al 2001). It is a leading cause of physical disability in childhood and is often associated with severe motor and other impairments (Table 1). Improved survival of small and premature babies who are particularly at risk of developing the condition raises concerns about increasing numbers of children with cerebral palsy possibly with more severe forms. In the UK, information about the number and needs of children with CP is not collected routinely. The most reliable sources of information on CP in the UK comes from five dedicated case registers which have monitored live births in their respective geographically defined areas since the 1960s and 1970s. These registers have formed a collaborative network called the United Kingdom Collaboration of Cerebral Palsy Registers (or UKCP) and are listed in Table 2. All five registers are currently funded and all are active in surveillance activities and research.

Characterization of a dielectric barrier discharge operating in an open reactor with flowing helium

A dielectric barrier discharge (DBD) generated by flowing helium between the parallel-plate electrodes of an open air reactor has been characterized using time resolved optical and electrical measurements. A sinusoidal voltage of up to 5 kV (peak to peak) of frequencies from 3 to 50 kHz has been applied to the discharge electrodes. The helium flow rate is varied up to 10 litre min(-1). The adjustment of flow rate allows the creation of uniform DBDs with optimized input power equal to 120 +/- 10 mW cm(-3). At flow rates from 4 to 6 litre min(-1) a uniform DBD is obtained. The maxima in the line intensities of N-2(+) and helium at 391.4 nm and 706.5 nm, respectively, 2 under those conditions indicate the importance of helium metastables and He-2(+) in sustaining such a discharge. The power efficiency and discharge 2 current show maxima when the DBD In He/air is uniform. The gas temperature during the discharge has been measured as 360 +/- 20 K.

Correlated electron-ion dynamics with open boundaries: formalism

We extend a new formalism, which allows correlated electron-ion dynamics to be applied to the problem of open boundary conditions. We implement this at the first moment level (allowing heating of ions by electrons) and observe the expected cooling in the classical part of the ionic kinetic energy and current-induced heating in the quantum contribution. The formalism for open boundaries should be easily extended to higher moments of the correlated electron-ion fluctuations.

'Prying open the space for social work in the new millennium: four theoretical perspectives on transformative practice'

Houston S, Skehill C, Pinkerton J & Campbell J (2005) Social Work and Social Sciences Review 12 (1) 35-52.

Neurodevelopmental and respiratory follow-up results at 7 years for children from the United Kingdom and Ireland enrolled in a randomized trial of early and late postnatal corticosteroid treatment, systemic and inhaled (the Open Study of Early Corticosteroid Treatment)

The goals were to compare early school-age neurodevelopmental and respiratory outcomes for children who were treated with either early (15 days) postnatal corticosteroid therapy and to compare systemic dexamethasone treatment with inhaled budesonide treatment.

Vandetanib with FOLFIRI in patients with advanced colorectal adenocarcinoma: results from an open-label, multicentre phase I study.

The safety and tolerability of vandetanib (ZACTIMA; ZD6474) plus FOLFIRI was investigated in patients with advanced colorectal cancer (CRC). METHODS: Patients eligible for first- or second-line chemotherapy received once-daily oral doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of FOLFIRI. RESULTS: A total of 21 patients received vandetanib 100 mg (n = 11) or 300 mg (n = 10) + FOLFIRI. Combination therapy was well tolerated at both vandetanib dose levels. There were no DLTs in the vandetanib 100 mg cohort and one DLT of hypertension (CTCAE grade 3) in the 300 mg cohort. The most common adverse events were diarrhoea (n = 20), nausea (n = 12) and fatigue (n = 10). Two patients (one in each cohort) discontinued vandetanib due to adverse events (rash, 100 mg cohort; hypertension, 300 mg cohort). There was no apparent pharmacokinetic interaction between vandetanib and FOLFIRI. Preliminary efficacy results included two confirmed partial responses in the 100 mg cohort and 9 patients with stable disease > or =8 weeks (100 mg, n = 7; 300 mg, n = 2). CONCLUSIONS: Once-daily vandetanib (100 or 300 mg) in combination with a standard FOLFIRI regimen was generally well tolerated in patients with advanced CRC.

Optimization of an open-ended microwave oven for microelectronics packaging

A physically open, but electrically shielded, microwave open oven can be produced by virtue of the evanescent fields in a waveguide below cutoff. The below cutoff heating chamber is fed by a transverse magnetic resonance established in a dielectric-filled section of the waveguide exploiting continuity of normal electric flux. In order to optimize the fields and the performance of the oven, a thin layer of a dielectric material with higher permittivity is inserted at the interface. Analysis and synthesis of an optimized open oven predicts field enhancement in the heating chamber up to 9.4 dB. Results from experimental testing on two fabricated prototypes are in agreement with the simulated predictions, and demonstrate an up to tenfold improvement in the heating performance. The open-ended oven allows for simultaneous precision alignment, testing, and efficient curing of microelectronic devices, significantly increasing productivity gains.