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Booth C.,University College London | Lawson S.,Birmingham Childrens Hospital NHS Foundation Trust | Veys P.,University College London
British Journal of Haematology | Year: 2013

Haematopoeitic stem cell transplantation (HSCT) is a curative procedure for children with malignant and non-malignant haematological disease as well as an expanding number of inherited disorders. Most patients lack a human leucocyte antigen-matched related donor, making alternative donors, such as closely matched unrelated donors, unrelated umbilical cord blood donations and haploidentical donors, necessary choices. T cell depletion (TCD) has been employed for over 30 years to reduce the risk of graft-versus-host disease (GvHD) associated with non-genoidentical HSCT. However, until recently overall survival had not improved with TCD due to increased rates of graft failure, disease relapse and delayed immune reconstitution. Recent advances in graft manipulation and reduced toxicity conditioning regimens have offered renewed hope, particularly for children undergoing haploidentical HSCT, where encouraging results have been achieved using negative depletion techniques to retain beneficial accessory cells, which speed immune reconstitution and reduce disease relapse. Translational work building on megadose CD34+ selected grafts, including pathogen-specific immunotherapy, suicide gene therapy and other adoptive cellular immunotherapies, has also offered improved outcomes for such patients. © 2013 John Wiley & Sons Ltd.


Reulen R.C.,University of Birmingham | Frobisher C.,University of Birmingham | Winter D.L.,University of Birmingham | Kelly J.,University of Birmingham | And 5 more authors.
JAMA - Journal of the American Medical Association | Year: 2011

Context: Survivors of childhood cancer are at excess risk of developing subsequent primary neoplasms but the long-term risks are uncertain. Objectives: To investigate long-term risks of subsequent primary neoplasms in survivors of childhood cancer, to identify the types that contribute most to long-term excess risk, and to identify subgroups of survivors at substantially increased risk of particular subsequent primary neoplasms that may require specific interventions. Design, Setting, and Participants: British Childhood Cancer Survivor Study - a population-based cohort of 17 981 5-year survivors of childhood cancer diagnosed with cancer at younger than 15 years between 1940 and 1991 in Great Britain, followed up through December 2006. Main Outcome Measures: Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of subsequent primary neoplasms. Results: After a median follow-up time of 24.3 years (mean=25.6 years), 1354 subsequent primary neoplasms were ascertained; the most frequently observed being central nervous system (n=344), nonmelanoma skin cancer (n=278), digestive (n=105), genitourinary (n=100), breast (n=97), and bone (n=94). The overall SIR was 4 times more than expected (SIR, 3.9; 95% confidence interval [CI], 3.6-4.2; AER, 16.8 per 10 000 person-years). The AER at older than 40 years was highest for digestive and genitourinary subsequent primary neoplasms (AER, 5.9 [95% CI, 2.5-9.3]; and AER, 6.0 [95%CI, 2.3-9.6] per 10 000 person-years, respectively); 36% of the total AER was attributable to these 2 subsequent primary neoplasm sites. The cumulative incidence of colorectal cancer for survivors treated with direct abdominopelvic irradiation was 1.4% (95% CI, 0.7%-2.6%) by age 50 years, comparable with the 1.2% risk in individuals with at least 2 first-degree relatives affected by colorectal cancer. Conclusion: Among a cohort of British childhood cancer survivors, the greatest excess risk associated with subsequent primary neoplasms at older than 40 years was for digestive and genitourinary neoplasms. ©2011 American Medical Association. All rights reserved.


Jenkinson H.,Birmingham Childrens Hospital NHS Foundation Trust
Archives of Disease in Childhood | Year: 2015

In the developed world, retinoblastoma is an uncommon yet highly curable ocular malignancy of childhood affecting 40-50 children in the UK each year. The presenting signs, most commonly leukocoria and squint, should alert the primary care physician or secondary care physician to examine for the red reflex, the absence of which is an indication for urgent ophthalmology assessment. Diagnosis is made by clinical examination and staging may include bone marrow sampling, lumbar puncture and MRI scanning. CT should be avoided to reduce radiation exposure in a population of whom a proportion are at considerable risk of second malignancies. Although enucleation is necessary for many children, over recent years there has been a growing emphasis on conservative management in an attempt to reduce the need for enucleation and avoid the adverse late effects associated with external beam radiotherapy. This review will describe approaches to treatment in the UK and how the stage, laterality and position of the tumour within the eye influence treatment choices.


Ewer A.K.,University of Birmingham | Middleton L.J.,University of Birmingham | Furmston A.T.,University of Birmingham | Bhoyar A.,Birmingham Childrens Hospital NHS Foundation Trust | And 4 more authors.
The Lancet | Year: 2011

Screening for congenital heart defects relies on antenatal ultrasonography and postnatal clinical examination; however, life-threatening defects often are not detected. We prospectively assessed the accuracy of pulse oximetry as a screening test for congenital heart defects. In six maternity units in the UK, asymptomatic newborn babies (gestation >34 weeks) were screened with pulse oximetry before discharge. Infants who did not achieve predetermined oxygen saturation thresholds underwent echocardiography. All other infants were followed up to 12 months of age by use of regional and national registries and clinical follow-up. The main outcome was the sensitivity and specificity of pulse oximetry for detection of critical congenital heart defects (causing death or requiring invasive intervention before 28 days) or major congenital heart disease (causing death or requiring invasive intervention within 12 months of age). 20 055 newborn babies were screened and 53 had major congenital heart disease (24 critical), a prevalence of 2·6 per 1000 livebirths. Analyses were done on all babies for whom a pulse oximetry reading was obtained. Sensitivity of pulse oximetry was 75·00 (95 CI 53·29-90·23) for critical cases and 49·06 (35·06-63·16) for all major congenital heart defects. In 35 cases, congenital heart defects were already suspected after antenatal ultrasonography, and exclusion of these reduced the sensitivity to 58·33 (27·67-84·83) for critical cases and 28·57 (14·64-46·30) for all cases of major congenital heart defects. False-positive results were noted for 169 (0·8) babies (specificity 99·16, 99·02-99·28), of which six cases were significant, but not major, congenital heart defects, and 40 were other illnesses that required urgent medical intervention. Pulse oximetry is a safe, feasible test that adds value to existing screening. It identifies cases of critical congenital heart defects that go undetected with antenatal ultrasonography. The early detection of other diseases is an additional advantage. National Institute for Health Research Health Technology Assessment programme. © 2011 Elsevier Ltd.


Zhou Y.,University of St. Andrews | Cameron E.,Birmingham Childrens Hospital NHS Foundation Trust | Forbes G.,University of St. Andrews | Humphris G.,University of St. Andrews
Patient Education and Counseling | Year: 2012

Objective: To develop and validate the St Andrews Behavioural Interaction Coding Scheme (SABICS): a tool to record nurse-child interactive behaviours. Methods: The SABICS was developed primarily from observation of video recorded interactions; and refined through an iterative process of applying the scheme to new data sets. Its practical applicability was assessed via implementation of the scheme on specialised behavioural coding software. Reliability was calculated using Cohen's Kappa. Discriminant validity was assessed using logistic regression. Results: The SABICS contains 48 codes. Fifty-five nurse-child interactions were successfully coded through administering the scheme on The Observer XT8.0 system. Two visualization results of interaction patterns demonstrated the scheme's capability of capturing complex interaction processes. Cohen's Kappa was 0.66 (inter-coder) and 0.88 and 0.78 (two intra-coders). The frequency of nurse behaviours, such as "instruction" (OR=1.32, p=0.027) and "praise" (OR=2.04, p=0.027), predicted a child receiving the intervention. Conclusions: The SABICS is a unique system to record interactions between dental nurses and 3-5 years old children. It records and displays complex nurse-child interactive behaviours. It is easily administered and demonstrates reasonable psychometric properties. Practice implications: The SABICS has potential for other paediatric settings. Its development procedure may be helpful for other similar coding scheme development. © 2012 Elsevier Ireland Ltd.

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