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Gale N.K.,University of Birmingham | Heath G.,University of Birmingham | Cameron E.,Aston University | Rashid S.,Lister Hospital | Redwood S.,University of Birmingham
BMC Medical Research Methodology | Year: 2013

Background: The Framework Method is becoming an increasingly popular approach to the management and analysis of qualitative data in health research. However, there is confusion about its potential application and limitations. Discussion. The article discusses when it is appropriate to adopt the Framework Method and explains the procedure for using it in multi-disciplinary health research teams, or those that involve clinicians, patients and lay people. The stages of the method are illustrated using examples from a published study. Summary. Used effectively, with the leadership of an experienced qualitative researcher, the Framework Method is a systematic and flexible approach to analysing qualitative data and is appropriate for use in research teams even where not all members have previous experience of conducting qualitative research. © 2013 Gale et al.; licensee BioMed Central Ltd.

News Article | October 26, 2016

“PEOPLE have told me what I do is dangerous. They have walked away from me at meetings,” says David Unwin, a doctor practising in Southport, UK. Unwin suggests to his patients with type 2 diabetes or who want to lose weight that they do the opposite of what official health advice recommends. He advises them to stop counting calories, eat high-fat foods – including saturated fats – and avoid carbohydrates, namely sugar and starch. Telling people to avoid sugar is uncontroversial; the rest is medical heresy. But crazy as it sounds, Unwin has found that most of his diabetes patients who follow this advice are getting their blood sugar back under control, and that some are coming off medication they have relied on for years. Those who are overweight are slimming down. This might seem like just another controversial fad diet, but a growing number of researchers, doctors and nutritionists around the world are backing it, and reporting their findings in peer-reviewed medical journals. Last month, the National Obesity Forum, a UK body for health professionals involved in weight management, made headlines when it overhauled its advice, telling people to ditch calorie-counting, low-fat foods and carbs in favour of fats. The recommendations provoked a furious backlash from mainstream scientists and dieticians, but they should concern us all. If the advice is to be believed, starchy food isn’t just bad for diabetes, it makes us fat and causes heart attacks. This is analogous to finding that smoking protects people from lung cancer, says David Haslam, an obesity specialist at the Lister Hospital in Stevenage, UK, and head of the

Wierzbicki A.S.,St Thomas Hospital Campus | Hardman T.C.,NICHE | Viljoen A.,Lister Hospital
Expert Opinion on Investigational Drugs | Year: 2012

Introduction: Pre-protein convertase subtilisin kexin (PCSK)-9 is a newly discovered protein involved in intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. Autosomal dominant activating mutations in PCSK-9 cause familial hypercholesterolaemia whereas inactivating mutations in man reduce LDL cholesterol (LDL-C) and are associated with a decreased lifetime risk of cardiovascular events. Areas covered: As PCSK-9 binds to the LDLR, a number of approaches involving small molecule or peptide inhibition of binding, antibody-mediated inactivation of binding and the use of antisense oligonucleotides are being investigated as therapeutic approaches to lower LDL-C in man. This article reviews the biochemistry and physiology of PCSK-9 and details the efforts made to design novel molecules with the ability to inhibit PCSK-9 activity. Work in animal models has confirmed that reducing PCSK-9 expression can reduce atherosclerosis in mice, rats and primates. Monoclonal antibodies such as REGN-727 and AMG-145 have been shown to reduce LDL-C in patients with familial hypercholesterolaemia already treated with statins or healthy normocholesterolaemic controls. Expert opinion: PCSK-9 inhibition is a potentially interesting novel addition to the armamentarium of LDL-C reducing drugs. Its effects in reducing LDL-C will need to be confirmed to reduce CVD events in large-scale clinical trials. © 2012 Informa UK, Ltd.

Bretherton C.P.,Lister Hospital | Parker M.J.,Peterborough City Hospital
The bone & joint journal | Year: 2015

There has been extensive discussion about the effect of delay to surgery on mortality in patients sustaining a fracture of the hip. Despite the low level of evidence provided by many studies, a consensus has been accepted that delay of > 48 hours is detrimental to survival. The aim of this prospective observational study was to determine if early surgery confers a survival benefit at 30 days. Between 1989 and 2013, data were prospectively collected on patients sustaining a fracture of the hip at Peterborough City Hospital. They were divided into groups according to the time interval between admission and surgery. These thresholds ranged from < 6 hours to between 49 and 72 hours. The outcome which was assessed was the 30-day mortality. Adjustment for confounders was performed using multivariate binary logistic regression analysis. In all, 6638 patients aged > 60 years were included. Worsening American Society of Anaesthesiologists grade (p < 0.001), increased age (p < 0.001) and extracapsular fracture (p < 0.019) increased the risk of 30-day mortality. Increasing mobility score (p = 0.014), mini mental test score (p < 0.001) and female gender (p = 0.014) improved survival. After adjusting for these confounders, surgery before 12 hours improved survival compared with surgery after 12 hours (p = 0.013). Beyond this the increasing delay to surgery did not significantly affect the 30-day mortality. ©2015 The British Editorial Society of Bone & Joint Surgery.

This post hoc analysis of the recently reported Frequent Hemodialysis Network Trials suggests that frequent nocturnal treatment, unlike frequent daily treatment, may be associated with more rapid loss of residual kidney function than conventional hemodialysis. Differences in blood pressure control, among other factors, may be implicated. The study invites reflection on our current concepts of the importance of preserving residual kidney function and on the indications for frequent treatments, particularly nocturnal. © 2013 International Society of Nephrology.

No imaging technique is more popular or more in demand than ultrasound. But should it be considered a specialist technique to be employed only by highly trained professionals or as a readily available tool to be used by many? This paper will discuss some of the implications of having ultrasound performed by a range of individuals and will emphasize the importance of training and regulation.

Wierzbicki A.S.,Guys and St Thomas Hospitals | Viljoen A.,Lister Hospital
Drug Safety | Year: 2010

Atherosclerosis begins in childhood with the formation of fatty streaks. Early plaques can be found in adolescence and early coronary disease can be found in young adults. It has been suggested that early treatment may lead to great benefits in later life. This article is a narrative review of the role of lipid-lowering drug therapy in paediatric practice.Increased rates of atherosclerosis are known to occur in children with familial hypercholesterolaemia (FH), especially in homozygotes. There is evidence for the efficacy and safety of lipid-lowering therapies in children, particularly with respect to the effects of HMG-CoA reductase inhibitors (statins) on lipids and, to a limited extent, on other surrogate measures of atherosclerosis in patients with FH. Diagnosis of FH and its early treatment are recommended in all guidelines. Lipid-lowering drug therapy is recommended for the treatment of homozygous FH at all ages and from as young as 10 years of age for the treatment of heterozygous FH when there is a family history of very premature coronary heart disease (occurring at age <40 years).Controversy exists about other possible indications. Increased rates of atherosclerosis are seen in autoimmune disorders, including type 1 diabetes mellitus, systemic lupus erythematosus and Kawasakis disease, and in transplant recipients. All evidence in these areas is derived by extrapolation from studies in adults. These disorders can be divided into those for which percutaneous coronary intervention is performed early andor for which drugs used to treat the primary disorder increase the rate of atherosclerosis, and those for which this is not the case. In both cardiac transplantation and Kawasakis disease, increased atherosclerosis can occur as a result of (i) disease-related vasculopathy; or (ii) increased restenosis secondary to interventions. Statins have a good evidence base for reducing rates of re-occlusion following coronary artery procedures, and this justifies their use in these settings. In renal transplantation, statins may have a role to play in patients with persistent dyslipidaemia and additional cardiovascular risk factors. In other disorders, such as type 1 diabetes, the disease process is atherogenic and thus statins may be justified in patients with a long history of disease (>10 years), poor control, and evidence of vascular or endothelial damage or additional cardiovascular risk factors.There is a role for lipid-lowering therapies in children at high risk of atherosclerosis, but the evidence base outside of FH is weak. Lipid-lowering therapy should be prescribed to all children with homozygous or severe heterozygous FH. Based on adult evidence, statin therapy should be considered in patients who have undergone coronary artery procedures or received cardiac transplants, in whom their primary role is to prevent vascular re-occlusion. In diseases associated with a chronic increased atherogenic risk, such as type 1 diabetes, statins should be considered in high-risk cases where additional cardiovascular risk factors are present.At present, the most important need is for trials to be performed in children using accepted surrogate endpoints to define whether lipid-lowering drug therapy is beneficial in this group. © 2010 Adis Data Information BV. All rights reserved.

Wierzbicki A.S.,Guys And St Thomas Hospitals | Viljoen A.,Lister Hospital
Expert Opinion on Biological Therapy | Year: 2013

Homozygous lipoprotein lipase (LPL) deficiency is an ultra-orphan disease associated with increased rates of pancreatitis. Current treatments based on acute plasmapheresis allied with ultra-low fat diets are inadequate as responses to fibrates or other triglyceride-lowering therapies tend to be poor. Alipogene tiparvovec is an adeno-associated virus type I (AAV1) gene therapy using a hyper-functional LPL serine447-stop (S447X) insert administered intramuscularly under general anaesthetic with allied immunosuppression. Treatment results in histological muscle expression of LPL allied with a transient 40% reduction in triglycerides and improvements in postprandial chylomicron triglyceride content. Alipogene tiparvovec is the first possibly curative treatment for LPL deficiency. © 2013 Informa UK, Ltd.

Smith A.H.,Lister Hospital
Emergency medicine journal : EMJ | Year: 2013

Massive haemorrhage still accounts for up to 40% of mortality after traumatic injury. The importance of limiting blood loss after injury in order to prevent its associated complications has led to rapid advances in the development of dressings for haemostatic control. Driven by recent military conflicts, there is increasing evidence to support their role in the civilian prehospital care environment. This review aims to summarise the key characteristics of the haemostatic dressings currently available on the market and provide an educational review of the published literature that supports their use. Medline and Embase were searched from start to January 2012. Other sources included both manufacturer and military publications. Agents not designed for use in prehospital care or that have been removed from the market due to significant safety concerns were excluded. The dressings reviewed have differing mechanisms of action. Mineral based dressings are potent activators of the intrinsic clotting cascade resulting in clot formation. Chitosan based dressings achieve haemostasis by adhering to damaged tissues and creating a physical barrier to further bleeding. Acetylated glucosamine dressings work via a combination of platelet and clotting cascade activation, agglutination of red blood cells and local vasoconstriction. Anecdotal reports strongly support the use of haemostatic dressings when bleeding cannot be controlled using pressure dressings alone; however, current research focuses on studies conducted using animal models. There is a paucity of published clinical literature that provides an evidence base for the use of one type of haemostatic dressing over another in humans.

Mazaris E.,Lister Hospital | Tsiotras A.,Lister Hospital
Nephro-Urology Monthly | Year: 2013

Objectives: Prostate cancer is a prevalent disease with a high impact on patients' morbidity and mortality. Despite efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with disease progression remain partially elusive. The purpose of this study is to review the recent evidence relating to the initiation and progression of prostate cancer in relation to the familial correlation of the disease, the genetic aberrations resulting in prostate cancer and the new molecular biology data regarding prostate cancer. Materials and Methods: A Medline database search identified all the existing publications on the molecular events associated with the pathogenesis and evolution of prostate cancer. Particular emphasis was given on the specific genetic phenomena associated with prostate cancer. Results: Like other cancers, prostate cancer is caused by an accumulation of genetic alterations in a cell that drives it to malignant growth. Specific genes and gene alterations have been suggested to play a role in its development and progression. Aneuploidy, loss of heterozygosity, gene mutations, hypermethylation and inactivation of specific tumour suppressor genes such as GSTpi, APC, MDR1, GPX3 and others have been detected in prostate cancers, but generally only at a low or moderate frequency. The androgen receptor (AR) signalling pathway may play a crucial role in the early development of prostate cancer, as well as in the development of androgenindependent disease that fails to respond to hormone deprivation therapies. Other alterations linked to the transition to hormoneindependence include amplification of MYC and increased expression of ERBB2 and BCL2. Inflammatory changes may also contribute to the development of prostate cancer. Conclusion: The identification of specific molecular markers for prostate cancer may lead to its earliest detection and better prediction of its behavior. The better understanding of the molecular events affecting prostate cancer progression may result in the introduction of new drugs to target these events thus providing a potential cure and a tool for prevention of this very common disease. © 2013, Nephrology and Urology Research Center; Published by Kowsar Corp.

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