Variation in treatment of acute childhood wheeze in emergency departments of the United Kingdom and Ireland: An international survey of clinician practice

© 2015, BMJ Publishing Group. All rights reserved. Objective: National clinical guidelines for childhood wheeze exist, yet despite being one of the most common reasons for childhood emergency department (ED) attendance, signi ficant variation in practice occurs in other settings. We, therefore, evaluated practice variations of ED clinicians in the UK and Ireland. Design: Two-stage survey undertaken in March 2013. Stage one examined department practice and stage two assessed ED consultant practice in acute childhood wheeze. Questions interrogated pharmacological and other management strategies, including inhaled and intravenous therapies. Setting and participants: Member departments of Paediatric Emergency Research in the United Kingdom and Ireland and ED consultants treating children with acute wheeze. Results: 30 EDs and 183 (81%) clinicians responded. 29 (97%) EDs had wheeze guidelines and 12 (40%) had care pathways. Variation existed between clinicians in dose, timing and frequency of inhaled bronchodilators across severities. When escalating to intravenous bronchodilators, 99 (54%) preferred salbutamol first line, 52 (28%) magnesium sulfate (MgSO4) and 27 (15%) aminophylline. 87 (48%) administered intravenous bronchodilators sequentially and 30 (16%) concurrently, with others basing approach on case severity. 146 (80%) continued inhaled therapy after commencing intravenous bronchodilators. Of 170 who used intravenous salbutamol, 146 (86%) gave rapid boluses, 21 (12%) a longer loading dose and 164 (97%) an ongoing infusion, each with a range of doses and durations. Of 173 who used intravenous MgSO4, all used a bolus only. 41 (24%) used non-invasive ventilation. Conclusions: Signi ficant variation in ED consultant management of childhood wheeze exists despite the presence of national guidance. This reflects the lack of evidence in key areas of childhood wheeze and emphasises the need for further robust multicentre research studies

Biophysical forcing of particle production and distribution during a spring bloom in the North Atlantic

Abstract: The beam attenuation serves as a proxy for particulate matter and is a key parameter in visibility algorithms for the aquatic environment. It is well known, however, that the beam attenuation is a function of the acceptance angle of the transmissometer used to measure it. Here we compare eight different transmissometers with four different acceptance angles using four different deployment strategies and sites, and find that their mean attenuation values differ markedly and in a consistent way with instrument acceptance angle: smaller acceptance angles provide higher beam attenuation values. This difference is due to variations in scattered light collected with different acceptance angles and is neither constant nor easy to parameterize. Variability (in space or time) in the ratios of beam attenuations measured by two different instruments correlates, in most cases, with the particle size parameter (as expected from Mie theory), but this correlation is often weak and can be the opposite of expectations based on particle size changes. We recommended careful consideration of acceptance angle in applications of beam transmission data especially when comparing data from different instruments

Biophysical forcing of particle production and distribution during a spring bloom in the North Atlantic

Abstract: The beam attenuation serves as a proxy for particulate matter and is a key parameter in visibility algorithms for the aquatic environment. It is well known, however, that the beam attenuation is a function of the acceptance angle of the transmissometer used to measure it. Here we compare eight different transmissometers with four different acceptance angles using four different deployment strategies and sites, and find that their mean attenuation values differ markedly and in a consistent way with instrument acceptance angle: smaller acceptance angles provide higher beam attenuation values. This difference is due to variations in scattered light collected with different acceptance angles and is neither constant nor easy to parameterize. Variability (in space or time) in the ratios of beam attenuations measured by two different instruments correlates, in most cases, with the particle size parameter (as expected from Mie theory), but this correlation is often weak and can be the opposite of expectations based on particle size changes. We recommended careful consideration of acceptance angle in applications of beam transmission data especially when comparing data from different instruments

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

The application of capillary electrophoresis for DNA polymorphism analysis

CE fractions may also be collected and then subjected to additional analysis. Nanoliter fractions containing size or shape fractionated DNA fragments can be collected on moving affinity membranes (125) or into sample chambers (126). The exact timing of the collection steps is achieved by determining the velocity of each individual zone measured between two detection points near the end of the capillary. The DNA samples may subsequently be identified by probe hybridization, or by PCR-linked sequencing. Capillary fractions containing metabolites and derivatives of DNA and small DNA adducts can also be sampled, and then characterized directly by highly sensitive MALDI-TOF atomic analysis (112-118) and ESI-MS (118,119). The automation and integration of PCR and CE analysis (PCR-CE) on a microchip (3-12,96) will also contribute greatly to its adoption as the analysis tool of choice. Significantly, these tools will be applied for DNA sequencing (75,108), for genome mapping (65) and genotyping (42-46), for improved certainty in disease detection (3-6,107,120) and for DNA mutation analysis (2-12,27,58). Recent improvements in the design CAE arrays and associated equipment such as the radial CAE microplate and rotary confocal signal detection system (127) overcome some of the detection limitations of linear CAE and microchip devices and allow the parallel genotyping of 96 samples in about 120 s. The integration of microreactive capillary surface assays (128) and "in-capillary" analysis will also lead to further increases in the speed and sensitivity of CE-based analysis. The recent announcement of the completion of the first draft sequence of the 90% of the entire human genome within 6 mo by Celera Genomics by sequencing random DNA fragments using several hundred ABI 3700 machines (129) illustrates the enormous efficiency realized through the automation of DNA sequencing by CAE. Sequencing was performed at an average rate of approximately 6 x 10(9) bases/yr. The CAE machines will now be employed for a concerted resequencing of genome elements to create an extremely high-density polymorphism map of the entire genome (130). This map will be based principally on single nucleotide polymorphisms, and will catapult human medicine into a new era of closely detailed genetic trait mapping to identify the genetic basis of multi-gene diseases

The enhancement of ribosomal transcription by the recycling of RNA polymerase I.

It has been suggested that the tandemly repeated ribosomal genes of eukaryotes may be subject to a special mechanism of transcriptional enhancement, called Readthrough Enhancement, in which transcription factors are recycled. Recent experiments with the mouse ribosomal genes, although consistent with this possibility, were unable to distinguish between true Readthrough Enhancement and promoter occlusion. To test directly for Readthrough Enhancement, the pre-ribosomal RNA of Xenopus laevis was prematurely terminated within the 18S gene on a circular template. This premature termination was found to reduce the efficiency of pre-ribosomal RNA promotion in cis by 80 to 90%. Since the pre-ribosomal RNA is normally terminated only 213 base pairs upstream of its own initiation site, the results strongly suggest that the recycling of RNA polymerase, or Readthrough Enhancement, is a means by which ribosomal transcription is enhanced in Xenopus laevis