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Muraro A.,University of Padua | Agache I.,Theramed Medical Center | Clark A.,Addenbrookes NHS Foundation Trust | Sheikh A.,University of Edinburgh | And 18 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early-childhood and school settings as well as providers of non-prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto-injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision-making on legislation at local and national level. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Cooke S.L.,Wellcome Trust Sanger Institute | Shlien A.,Wellcome Trust Sanger Institute | Marshall J.,Wellcome Trust Sanger Institute | Pipinikas C.P.,University College London | And 46 more authors.
Nature Communications | Year: 2014

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5a €2 truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context. © 2014 Macmillan Publishers Limited. All rights reserved.


Varghese J.S.,Center for Cancer Genetic Epidemiology | Varghese J.S.,Royal Free Hospital | Smith P.L.,Center for Cancer Genetic Epidemiology | Folkerd E.,Royal Marsden Hospital | And 7 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2012

Background: Mammographic breast density and endogenous sex-hormone levels are both strong risk factors for breast cancer. This study investigated whether there is evidence for a shared genetic basis between these risk factors. Methods: Using data on 1,286 women from 617 families, we estimated the heritabilities of serum estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels and of three measures of breast density (dense area, nondense area, and percentage density). We tested for associations between hormone levels and density measures and estimated the genetic and environmental correlations between pairs of traits using variance and covariance components models and pedigree-based maximum likelihood methods. Results: We found no significant associations between estradiol, testosterone, or SHBG levels and any of the three density measures, after adjusting for body mass index (BMI). The estimated heritabilities were 63%, 66%, and 65% for square root-transformed adjusted percentage density, dense area, and nondense area, respectively, and 40%, 25%, and 58% for log-transformed-adjusted estradiol, testosterone, and SHBG. We found no evidence of a shared genetic basis between any hormone levels and any measure of density, after adjusting for BMI. The negative genetic correlation between dense and nondense areas remained significant even after adjustment for BMI and other covariates (ρ = -0.34; SE = 0.08; P = 0.0005). Conclusions: Breast density and sex hormones can be considered as independent sets of traits. Impact: Breast density and sex hormones can be used as intermediate phenotypes in the search for breast cancer susceptibility loci. ©2012 AACR.


Homer J.R.,Alder Hey Childrens NHS Foundation Trust | Bass S.,Addenbrookes NHS Foundation Trust
Paediatric Anaesthesia | Year: 2010

Objectives: To discover whether any consensus exists among the Association of Paediatric Anaesthetists of Great Britain and Ireland (APA) members regarding the use and acceptability (or otherwise) of physical restraint. Background: Despite growing recognition of children's right to be consulted regarding their healthcare, the issue of how to proceed when faced with a child unwilling to undergo induction of general anesthesia remains relatively unaddressed. Methods: APA members were surveyed regarding their use or avoidance of physical restraint and alternate techniques to facilitate induction; factors affecting choice of technique; and extent of preoperative discussion. The anonymous online survey used both structured and free text responses. Results: Of 596 surveys, 310 were returned, a 52% response rate. Use of physical restraint and extent of restraint employed declines with increasing child age. Distraction techniques are frequently employed for children under 6 years, with the use of sedative premedication increasing as child age increases. Urgency of procedure, developmental delay, and preoperative discussion all have an effect. Comments demonstrated a wide range of views and lack of consensus on what constitutes physical restraint, and what degree of restraint, if any, is acceptable. Conclusion: Our results are similar to the US Society of Pediatric Anesthesia members, suggesting this remains an issue internationally. Consideration of practices in other specialties gives some guidance. Our survey shows a range of views as to what physical restraint is or involves, and what constitutes acceptable practice regarding the use or avoidance of physical restraint. We were unable to demonstrate consensus. © 2010 Blackwell Publishing Ltd.


Quinnell T.G.,Papworth Hospital NHS Foundation Trust | Bennett M.,University of Cambridge | Jordan J.,Brunel University | Clutterbuck-James A.L.,Papworth Hospital NHS Foundation Trust | And 12 more authors.
Thorax | Year: 2014

Rationale: Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives: To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods: This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5-<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results: 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions: Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice. Trial registration number ISRCTN02309506.


PubMed | Imperial College London, Brunel University, University of Leeds, Papworth Hospital NHS Foundation Trust and 2 more.
Type: Comparative Study | Journal: Thorax | Year: 2014

Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease.To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS.This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5-<30/h and Epworth Sleepiness Scale (ESS) score 9 underwent 6weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost.90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a 20,000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to 39,800/QALY.Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice.ISRCTN02309506.


Powles R.,Parkside Cancer Center | Sirohi B.,Addenbrookes NHS Foundation Trust | Niederwieser D.,University of Leipzig
Health Physics | Year: 2010

The European Blood and Marrow Transplantation Society's Nuclear Accident Committee has been a catalyst in bringing together consensus on the triage, Service Configuration, and care that might effectively be given by haematologists in the event of a massive irradiation incident. Further coordinated and integrated effort will be needed at European, international, and national levels to allow unified guidelines to treat such patients. The role of the training haematologist and devising a European Network of effective Service Configuration is the key to delivering an effective response if a major incident occurred. Copyright © 2010 Health Physics Society.

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