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Nottingham, United Kingdom

Background/Objectives:Children with Crohn’s disease often demonstrate nutritional recovery during primary therapy at diagnosis, but long-term nutritional support is sometimes necessary. Evidence to inform best nutritional practice including energy and micronutrient requirements is limited. The principal objective of this study was to determine how energy expenditure and physical activity vary with disease activity over the first year following diagnosis.Subjects/Methods:Twenty children were studied at diagnosis with Crohn’s disease and were followed up over 1 year while receiving treatment according to national guidelines. The majority of children (13) were treated with exclusive enteral nutrition. At study visits, height, weight, bioelectrical impedance, resting energy expenditure by indirect calorimetry, tri-axial accelerometer and blood investigations were performed alongside clinical assessment.Results:There was no significant effect of disease activity on resting energy expenditure (REE). Physical activity was greater after primary therapy (Z=3.31, P<0.01). Median wPCDAI fell from 58 at diagnosis to 7.5 after primary therapy and was 7.5 at 1 year. Weight s.d.s increased from −1.67 to −0.86 and lean index s.d.s increased from −2.93 to −1.64, although the increase was mostly in the first 2 months. Median height s.d.s was unchanged throughout this study. There was a significant association between dietary intake and weight gain (r=0.8 P<0.01) but not height gain. Persistent micronutrient deficits beyond diagnosis were seen for both iron and vitamin D.Conclusions:This study has demonstrated that REE does not change significantly through different phases of disease activity, but physical activity is low at diagnosis. Children with Crohn's disease should be screened for deficiencies of iron and vitamin D.European Journal of Clinical Nutrition advance online publication, 22 June 2016; doi:10.1038/ejcn.2016.107. © 2016 Macmillan Publishers Limited Source


Fox M.,NIHR Biomedical Research Unit
Neurogastroenterology and Motility | Year: 2012

Background Weak and absent esophageal peristalsis are frequently encountered esophageal motility disorders, which may be associated with dysphagia and which may contribute to gastroesophageal reflux disease. Recently, rapid developments in the diagnostic armamentarium have taken place, in particular, in high-resolution manometry with or without concurrent intraluminal impedance monitoring. Purpose This article aims to review the current insights in the terminology, pathology, pathophysiology, clinical manifestations, diagnostic work-up,and management of weak and absent peristalsis. © 2012 Blackwell Publishing Ltd. Source


Fox M.,NIHR Biomedical Research Unit | Sweis R.,Oesophageal Laboratory
Neurogastroenterology and Motility | Year: 2012

Background Symptom based diagnosis is not reliable in patients with swallowing problems, heartburn, and other dyspeptic complaints. The aim of investigation is to provide clinically relevant measurements of gastrointestinal structure and function that explain the cause of symptoms, identify pathology, and guide effective management. Current practice rarely meets these ideals. Purpose This review considers recent advances in technology such as high-resolution manometry (HRM) with esophageal pressure topography (EPT), HRM with impedance, high frequency ultrasound, and endoscopic functional luminal impedance planimetry (Endo-FLIP) that provide new opportunities to identify the pathophysiologic basis of esophageal symptoms and disease. As experience with these new devices increases researchers are developing new methodologies that maximize their utility in clinical practice. For example, application of HRM to assess motility and function during and after a test meal can identify the causes of swallowing problems, reflux and other postprandial symptoms and intra-operative application of Endo-FLIP may help surgeons perform antireflux surgery. These examples illustrate the potential of physiologic measurement to direct rational and effective clinical management for individual patients. © 2012 Blackwell Publishing Ltd. Source


Buch M.H.,University of Leeds | Buch M.H.,NIHR Biomedical Research Unit | Rubbert-Roth A.,University of Cologne | Ferraccioli G.,Catholic University of the Sacred Heart
Autoimmunity Reviews | Year: 2012

The introduction in the therapeutic armamentarium of TNF inhibitors (TNFi) has greatly advanced the chance of obtaining a control of clinical manifestations and of structural damage progression in an important proportion of patients with rheumatoid arthritis (RA) Methotrexate (MTX)-poor responders. However not more than 50% of TNFi treated patients can reach relevant clinical benefits. Therefore the unmet medical question is: should we continue the therapeutic approach with a second or a third TNFi, or should we use other drugs, and change the mode of action of the second drug? These are practical issues that still do not have a definite answer. The real problem is that up to this moment no real biomarker is available to make the appropriate choice. The only clear-cut biomarker is represented by the positivity of rheumatoid factor (RF) or anti citrullinated peptide autoantibodies (ACPA). Seropositive patients seem to respond better than seronegative ones to B cell depletion therapy (Rituximab). This paper discusses the pros and cons of switching or swapping in RA patients poorly responder to the first TNFi. © 2011 Elsevier B.V. Source


Chung K.F.,Imperial College London | Chung K.F.,NIHR Biomedical Research Unit
Drugs | Year: 2014

Asthma is a common disease with a complex pathophysiology. It can present in various clinical forms and with different levels of severity. Unbiased cluster analytic methods have unravelled several phenotypes in cohorts representative of the whole spectrum of severity. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, usually associated with severe airflow obstruction. Phenotypes with concordance between symptoms and sputum eosinophilia have been reported, including an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper (Th)-2 cytokine, interleukin (IL)-5. Low Th2-expression has been predictive of poor therapeutic response to inhaled corticosteroid therapy. Current asthma schedules emphasise a step-up approach to treating asthma in relation to increasing severity, but, in more severe disease, phenotyping or endotyping of asthma will be necessary to determine new treatment strategies as severe asthma is recognized as being a particularly heterogeneous disease. Much less is known about 'non-eosinophilic' asthma. Phenotypic characterisation of corticosteroid insensitivity and chronic airflow obstruction of severe asthma is also needed. Phenotype-driven treatment of asthma will be further boosted by the advent of transcriptomic and proteomic technologies, with the application of systems biology or medicine approaches to defining phenotypes and biomarkers of disease and therapeutic response. This will pave the way towards personalized medicine and healthcare for asthma. © 2014 Springer International Publishing Switzerland. Source

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