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Kelly R.J.,Leeds Teaching Hospitals Trust | Hill A.,Leeds Teaching Hospitals Trust | Arnold L.M.,Leeds Teaching Hospitals Trust | Brooksbank G.L.,Leeds Teaching Hospitals Trust | And 6 more authors.
Blood | Year: 2011

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder with increased mortality and morbidity resulting from intravascular hemolysis. Eculizumab, a monoclonal antibody against the complement protein 5, stops the intravascular hemolysis in PNH. We evaluated 79 consecutive patients treated with eculizumab in Leeds between May 2002 and July 2010. The survival of patients treated with eculizumab was not different from age- and sexmatched normal controls (P = .46) but was significantly better than 30 similar patients managed before eculizumab (P = .030). Three patients on eculizumab, all over 50 years old, died of causes unrelated to PNH. Twenty-one patients (27%) had a thrombosis before starting eculizumab (5.6 events per 100 patientyears) compared with 2 thromboses on eculizumab (0.8 events per 100 patientyears; P < .001). Twenty-one patients with no previous thrombosis discontinued warfarin on eculizumab with no thrombotic sequelae. Forty of 61 (66%) patients on eculizumab for more than 12 months achieved transfusion independence. The 12-month mean transfusion requirement reduced from 19.3 units before eculizumab to 5.0 units in the most recent 12 months on eculizumab (P < .001). Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to a similar level to that of the general population. © 2011 by The American Society of Hematology.


Haeusler G.M.,Royal Melbourne Hospital | Haeusler G.M.,Peter MacCallum Cancer Center | Carlesse F.,Federal University of São Paulo | Phillips R.S.,University of York | Phillips R.S.,Leeds Teaching Hospitals Trust
Pediatric Infectious Disease Journal | Year: 2013

Background: Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. The role of biomarkers in predicting morbidity and mortality associated with FN in children has been explored with varying results. This systematic review identified, critically appraised and synthesized information on the use of biomarkers for the prediction of outcome of FN in children/young adults, updating a review of initial assessment and adding further analysis of their value at reassessment. Methods: This review was conducted in accordance with the Centre for Reviews and Dissemination Methods, using 3 different random effects meta-analysis models. Results: Thirty-seven studies involving over 4689 episodes of FN in children were assessed, including an additional 13 studies investigating 18 biomarkers in 1670 FN episodes since the original review. Meta-analysis was possible for admission C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 and interleukin-8 in their ability to detect significant infection. Marked heterogeneity exists, precluding clear clinical interpretation of the results. Qualitative synthesis of the role of serial biomarkers suggests their predictive ability may be more pronounced at 24 to 48 hours compared with admission. Direct comparisons of the discriminatory power of admission values of PCT and CRP showed PCT generally had a better discriminatory estimate of serious infection than CRP. Conclusions: There remains a paucity of robust and reproducible data on the use of biomarkers in prediction of serious infection in children with FN. Available evidence suggests PCT has better discriminatory ability than CRP and that the role of serial biomarkers warrants further study. Copyright © 2013 by Lippincott Williams & Wilkins.


Minks D.P.,Leeds Teaching Hospitals Trust | Porte M.,York Teaching Hospital NHS Foundation Trust | Jenkins N.,York Teaching Hospital NHS Foundation Trust
Clinical Radiology | Year: 2013

Acute mastoiditis is a commonly occurring condition in children and adults, and one that most radiologists will come across at some point during their on-call duties. Acute mastoiditis is usually clinically apparent. However, the complications, especially the intracranial ones, can be more insidious and may have fatal consequences. Therefore, it is imperative that the radiologist is well versed in identifying these. Local spread of infection from the mastoids and middle ear cleft may occur via four routes: bone erosion, thrombophlebitis, periphlebitis, and via the anatomical pathways. The role of radiology is largely to demonstrate the complications of mastoiditis, which can be clinically occult and are often serious; this article will highlight these complications. © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.


Emery P.,University of Leeds | Emery P.,Leeds Teaching Hospitals Trust | Dorner T.,Charité - Medical University of Berlin
Annals of the Rheumatic Diseases | Year: 2011

Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients.


Rusu A.C.,Royal Holloway, University of London | Rusu A.C.,Ruhr University Bochum | Pincus T.,Royal Holloway, University of London | Morley S.,University of Leeds | Morley S.,Leeds Teaching Hospitals Trust
Pain | Year: 2012

Depression is a common feature of chronic pain, but there is limited research into the content and frequency of depressed cognitions in pain patients. A limitation of previous research is the failure to include nonpain depressed comparison groups. The present study used a sentence completion task to investigate the content of cognition in 4 groups of participants: with pain and concurrent depression, pain without depression, depression without pain, and with neither pain nor depression. One hundred seventy-two participants generated sentences to a set of predefined stems. Complete responses were coded by affective valence (negative, positive, and neutral) and health-related content. As predicted, participants with depression (with and without pain) produced more negative responses than nondepressed participants (with and without pain); participants with pain (depressed and nondepressed) produced more health responses than those without pain (depressed and controls); participants with depression and pain produced more negative health responses than any other group. The strengths of the current study are the inclusion of the depressed nonpain group, the use of a comprehensive coding scheme applied by 2 independent raters, and the presence of depression validated through a diagnostic interview. In contrast to depressed groups without pain, participants with pain and depression exhibit a cognitive bias specific to negative aspect of health. This focus facilitates understanding of the relationship between depression and pain processing: The implications for therapeutic interventions are discussed. © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Limb D.,Leeds Teaching Hospitals Trust
Bone and Joint Journal | Year: 2014

Continuing professional development (CPD) refers to the ongoing participation in activities that keep a doctor up to date and fit to practise once they have completed formal training. It is something that most will do naturally to serve their patients and to enable them to run a safe and profitable practice. Increasingly, regulators are formalising the requirements for evidence of CPD, often as part of a process of revalidation or relicensing. This paper reviews how orthopaedic journals can be used as part of the process of continuing professional development. ©2014 The British Editorial Society of Bone & Joint Surgery.


Speight R.,St James's Hospital | Sykes J.,St James's Hospital | Lindsay R.,St James's Hospital | Franks K.,Leeds Teaching Hospitals Trust | Thwaites D.,St James's Hospital
Radiotherapy and Oncology | Year: 2011

Purpose: To evaluate a deformable image registration (DIR) segmentation technique for semi-automating ITV production from 4DCT for lung patients, in terms of accuracy and efficiency. Methods: Twenty-five stereotactic body radiotherapy lung patients were selected in this retrospective study. ITVs were manually delineated by an oncologist and semi-automatically produced by propagating the GTV manually delineated on the mid-ventilation phase to all other phases using two different DIR algorithms, using commercial software. The two ITVs produced by DIR were compared to the manually delineated ITV using the dice similarity coefficient (DSC), mean distance between agreement and normalised DSC. DIR-produced ITVs were assessed for their clinical suitability and also the time savings were estimated. Results: Eighteen out of 25 ITVs had normalised DSC > 1 indicating an agreement with the manually produced ITV within 1 mm uncertainty. Four of the other seven ITVs were deemed clinically acceptable and three would require a small amount of editing. In general, ITVs produced by DIR were smoother than those produced by manual delineation. It was estimated that using this technique would save clinicians on average 28 min/patient. Conclusions: ABAS was found to be a useful tool in the production of ITVs for lung patients. The ITVs produced are either immediately clinically acceptable or require minimal editing. This approach represents a significant time saving for clinicians. © 2010 Elsevier Ireland Ltd. All rights reserved.


Yates H.L.,Leeds Teaching Hospitals Trust | Newell S.J.,University of Leeds
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2011

Objective: Postnatal dexamethasone therapy is controversial. This study aimed to determine the short-term effects of Minidex (low-dose dexamethasone 0.05 mg/kg/day) on ventilator-dependent preterm babies. Methods: Very preterm babies (less than 30 weeks of gestation or under 1500 g) who were ventilator dependent at over 2 weeks of life and received Minidex therapy (low-dose dexamethasone 0.05 mg/ kg/ day for 10 days followed by alternate-day doses for 6 days) were compared retrospectively to a matched comparison group who received neither Minidex nor standard-dose dexamethasone. Results: 50 babies who received Minidex were compared to a comparison group of 26 babies. Babies treated with Minidex extubated significantly faster than controls, Cox regression hazard ratio 6.24 (95% CI 2.34 to 16.63). By day 4, 34% of babies treated with Minidex had extubated but no controls had. Babies who received Minidex showed significant improvements in both ventilatory index and oxygen requirements, had no increased rate of clinical hypertension (OR 1.16 (95% CI 0.42 to 3.21)) or hyperglycaemia (OR 1.55 (95% CI 0.44 to 5.45)) and had a similar rate of chronic lung disease at 36 weeks' corrected age (OR 1.61 (95% CI 0.62 to 4.22)). No baby developed gastrointestinal perforation or haemorrhage. Conclusion: Minidex therapy facilitates extubation and is not associated with clinically significant short-term side effects. A randomised controlled trial is required to further assess efficacy and long-term outcomes.


Harrison C.,Leeds Teaching Hospitals Trust | McKechnie L.,Leeds Teaching Hospitals Trust
Acta Paediatrica, International Journal of Paediatrics | Year: 2012

Aims: Discomfort and stress have been widely studied in the newborn baby but data are lacking for the infant undergoing transport. The aim of our study was to identify infant discomfort during road transport and its pattern. Methods: This was a prospective cohort study on all infants transported by the Yorkshire Neonatal Transport Service over a 6-month period. The same environmental measures were used for each baby. The premature infant pain profile was used to measure stress and discomfort at five specified times during transport. The score before any intervention was the gold standard. Results: Of 239 transport episodes, 140 had complete data. Twenty-four babies were ventilated and routinely sedated with morphine, and the remaining babies had no pain relief. The same pattern of premature infant pain profile (PIPP) score was seen in all infants regardless of gestation or sedation. The raw PIPP scores (and data when ranked) peaked during road transport, and this was a significant change compared to baseline observations. This pattern was consistent across all gestational age groups. The sedated/ventilated babies showed the same pattern although it was blunted. Conclusion: All babies showed higher levels of discomfort during transport compared to baseline. More work is needed to develop interventions that could potentially decrease this. © 2011 The Author(s)/Acta Pßdiatrica.


Yates H.L.,Leeds Teaching Hospitals Trust | Newell S.J.,Leeds Teaching Hospitals Trust
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2012

Postnatal steroids have been widely used to facilitate the extubation of ventilator-dependent preterm infants. Reports published in the late 1990s and early 2000s raised concerns about their long-term impact on neurodevelopmental outcomes. Since then, postnatal steroid use has declined sharply, but they continue to be regarded by many clinicians as an essential part of neonatal care, and there is considerable confusion as to the most appropriate time to use them. This review examines the meta-analyses of the relationship between intravenous postnatal steroids and neurodevelopmental impairment, and provides recommendations for their use based upon that body of evidence.

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