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Balfour-Lynn I.M.,Royal Brompton Hospital
Cochrane database of systematic reviews (Online) | Year: 2012

Reduction of lung inflammation is one of the goals of cystic fibrosis (CF) therapy. Inhaled corticosteroids (ICS) are often used to treat children and adults with CF. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of ICS, especially in the light of their known adverse effects on growth. To assess the effectiveness of taking regular ICS, compared to not taking them, in children and adults with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.Date of most recent search of the Group's Trials Register: 03 September 2012. Randomised or quasi-randomised trials, published and unpublished, comparing ICS to placebo or standard treatment in individuals with CF. Two independent authors assessed methodological quality of trials using established criteria and extracted data using standard pro formas. The searches identified 34 citations, of which 26 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of ICS in 506 people with CF aged between 6 and 55 years. One trial was a withdrawal study in individuals who were already taking ICS. Methodological quality was difficult to assess from published information. Inclusion criteria varied between trials, as did type and duration of treatment and timing of outcome assessments. Objective measures of airway function were reported in most trials but were often incomplete. Significant benefit has not been conclusively demonstrated. Four trials systematically documented adverse effects and growth was significantly affected in one study using high doses. Evidence from these trials is insufficient to establish whether ICS are beneficial in CF, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial. Source


Sheppard M.N.,Royal Brompton Hospital
International Journal of Legal Medicine | Year: 2011

Cystic tumour of the atrioventricular nodal region is a rare primary cardiac tumour that can cause sudden death. Antemortem diagnosis and successful excision of this type of tumour are extremely rare. Three cases of sudden death are reported: A 25- and 40-year-old with a history of heart block and a 60-year-old with no medical history. There have been more than 120 cases of sudden death attributed to primary cardiac tumours in the literature. Although over 100 of these lesions were histologically benign, their intracardiac locations precipitated conductive and haemodynamic abnormalities that resulted in sudden death. The most common intracardiac lesion causing sudden death, cystic tumour of the atrioventricular node, however, may not be discovered unless the atrioventricular node is microscopically examined. © 2009 Springer-Verlag. Source


Davidson S.,Royal Brompton Hospital
British Journal of Haematology | Year: 2014

Over 35 000 cardiac operations using cardiopulmonary bypass are performed annually in the UK. Post-operative bleeding is a common cause of morbidity. Although there have been improvements in surgical techniques, recent publications still show post-operative blood loss to be significant, with allogeneic blood product usage as high as 50%. Despite greater understanding of the mechanisms of the coagulopathy encountered during cardiac surgery the development of treatment options has been slow. There has been a realization of the inadequacy of fresh frozen plasma to correct the coagulopathy in this setting, leading to greater off-label use of specific factor concentrates to stop bleeding, e.g., prothrombin complex concentrates and fibrinogen concentrates. Recent trials using factor XIII and IX concentrates have not been successful. This article will review preventative measures to reduce post-operative bleeding and the current management of bleeding with such factor concentrates and, in most cases, the limited evidence supporting their widespread use. © 2014 John Wiley & Sons Ltd. Source


Balfour-Lynn I.M.,Royal Brompton Hospital
Paediatric Respiratory Reviews | Year: 2014

Personalised medicine refers to a tailored approach to treatment of an individual based on molecular analysis of genes, proteins or metabolites, and commonly involves a companion diagnostic test. It usually applies to small subsets of patients, often with rare diseases. In cystic fibrosis (CF), the best example is the CFTR (CF transmembrane conductance regulator) potentiator, ivacaftor, relevant to the 5% of cystic fibrosis patients with the p.Gly551Asp gene mutation. However the cost of personalised medicine is too high, making it unaffordable in the long term for many healthcare systems. Society needs to find a way to make personalised medicine affordable in order to not deny life-changing treatments from patients. © 2014 Elsevier Ltd. Source


Tan H.-L.,Imperial College London | Rosenthal M.,Royal Brompton Hospital
Thorax | Year: 2013

Interleukin 17 (IL-17) is a key proinflammatory cytokine in the T helper 17 pathway. While it is important in the clearance of certain pathogens, IL-17 has been shown to contribute to the pathogenesis of such inflammatory diseases as rheumatoid arthritis and psoriasis. In the lung, it has been postulated to be involved in the neutrophilic inflammation and airway remodelling of chronic respiratory conditions but the situation is increasingly complex. This review summarises the evidence for its role in several chronic inflammatory lung diseases: asthma, obliterative bronchiolitis, chronic obstructive pulmonary disease, sarcoidosis and cystic fibrosis. Source

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