Guys And St Thomas Hospitals

London, United Kingdom

Guys And St Thomas Hospitals

London, United Kingdom

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Siablis D.,University of Patras | Kitrou P.M.,University of Patras | Spiliopoulos S.,University of Patras | Katsanos K.,Guys And St Thomas Hospitals | Karnabatidis D.,University of Patras
JACC: Cardiovascular Interventions | Year: 2014

Background DES have an established role in the treatment of short infrapopliteal lesions, whereas there is increasing evidence for the use of PCB in longer below-the-knee lesions.Methods Inclusion criteria were patients with Rutherford classes 3 to 6 and angiographically documented infrapopliteal disease with a minimum lesion length of 70 mm. The primary endpoint was target lesion restenosis >50% assessed by digital angiography at 6 months. Secondary endpoints included immediate post-procedure stenosis and target lesion revascularization.Results Fifty patients were randomized to undergo infrapopliteal PCB angioplasty (25 arteries in 25 limbs; PCB group) or primary DES placement (30 arteries in 27 limbs; DES group). Immediate residual post-procedure stenosis was significantly lower in DES (9.6 ± 2.2% vs. 24.8 ± 3.5% in PCB; p < 0.0001). At 6 months, 5 patients died (2 in PCB vs. 3 in DES; p = 1.00) and 3 suffered a major amputation (1 in PCB vs. 2 in DES; p = 1.00). In total, 44 angiograms were evaluable with quantitative vessel analysis. Binary (>50%) angiographic restenosis rate was significantly lower in DES (7 of 25 [28%] vs. 11 of 19 [57.9%] in PCB; p = 0.0457). There were no significant differences with regard to target lesion revascularization (2 of 26 [7.7%] in DES vs. 3 of 22 [13.6%] in PCB; p = 0.65). Positive vessel wall remodeling was observed in 3 cases in the PCB arm (3 of 19 [(15.8%)] vs. 0 of 19 [0%] in DES; p = 0.07).Conclusions Compared with PCB in long infrapopliteal lesions, DES are related with significantly lower residual immediate post-procedure stenosis and have shown significantly reduced vessel restenosis at 6 months. PCB may produce positive vessel remodeling. (Infrapopliteal Drug-Eluting Angioplasty Versus Stenting [IDEAS-I]; NCT01517997).Objectives This study sought to report the results of a prospective randomized controlled trial comparing paclitaxel-coated balloons (PCB) versus drug-eluting stents (DES) in long infrapopliteal lesions. © 2014 American College of Cardiology Foundation.


Hopkins C.,Guys And St Thomas Hospitals | Rimmer J.,Nose and Ear Hospital | Lund V.J.,Nose and Ear Hospital
Rhinology | Year: 2015

Objectives: Patients with chronic rhinosinusitis refractory to medical management undergo elective surgery. The time from initial diagnosis to surgery varies considerably. The impact of this delay on surgical success has never previously been evaluated. Design: First-time patients within the National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis were grouped based on time to surgery: 1) Early cohort: < 12 months; 2) Mid cohort: 12-60 months; and 3) Late cohort: > 60 months. Co-morbidities and preoperative CT scores were analysed for all patients. Main outcome measures: The 22-item Sino-Nasal Outcome Test scores (SNOT-22) were collected at 0, 3, 12 and 60-months. Absolute and relative SNOT-22 changes from baseline were evaluated. Results: Asthma and allergies were significantly more prevalent in the Late versus the Early and Mid-cohorts. In addition, patients in the Late cohort had greater symptom burden on the SNOT-22 and more extensive preoperative radiographic disease as determined by Lund-Mackay (LM) scores. SNOT-22 scores demonstrated greater percentage improvements in the Early versus the Midand Late cohorts, at all time points after surgery. At 12 and 60 months after surgery, significantly more patients in the Early group achieved a clinically important change in SNOT-22 scores compared with the other groups. These differences were maintained when cohorts were matched for preoperative co-morbidities. Conclusion: Patients with asthma and/or allergies are more likely to experience delayed surgical intervention versus other patients. Overall, patients with delayed surgery reported less improvement in SNOT-22 scores than patients treated at earlier time points, regardless of co-morbid status. Delaying surgical intervention may worsen long term clinical outcomes. © 2015, AMC. All rights reserved.


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.


Wierzbicki A.S.,St Thomas Hospital | Oben J.,Guys And St Thomas Hospitals
Current Opinion in Lipidology | Year: 2012

Purpose of Review: This article reviews the mechanisms leading to the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and the effects of hypoglycaemic and lipid-lowering therapies on NAFLD/NASH. Recent Findings: The interaction of lipogenesis, fatty acid oxidation, inflammation, endoplasmic reticulum stress and hepatic insulin resistance contribute to the pathogenesis of NAFLD/NASH. Few large scale clinical trials exist with biopsy or magnetic resonance endpoints as opposed to ultrasonographic and transaminase endpoints. Trial evidence that exists supports the utility of weight loss, metformin, thiazolidinediones, fibrates, niacin, ezetimibe and statins in improving the steatosis component of NAFLD/NASH though with less or minimal effects on the fibrotic component of NASH. Summary: Hypoglycaemic and lipid-lowering therapies may have a role in the treatment of NAFLD/NASH but large scale endpoint trials remain to be performed. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Anagnostou K.,Guys and St Thomas Hospitals | Clark A.,University of Cambridge
Archives of Disease in Childhood | Year: 2015

Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies such as egg and milk. Measures aiming to reduce its prevalence via maternal avoidance during pregnancy and lactation, or delayed introduction into the diet, have failed to show any benefit. Peanut allergy has a significant effect on the quality of life of sufferers and their families due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication. Families find avoidance challenging as peanut is hidden in various food products. Despite the fact that food labelling has improved, with a legal obligation to declare certain food allergens (including nuts) in prepacked products, it still causes confusion and does not extend to cross-contamination. In an effort to address issues of safety at school, a lot of work has been undertaken to better care for peanut-allergic children in that environment. This includes training of school staff on how to recognise and treat allergic reactions promptly. Recent developments in the management of peanut allergy, such as immunotherapy, have shown some promise as an active form of treatment, but larger studies are required to further investigate safety and efficacy.


Ewang-Emukowhate M.,Guys and St Thomas Hospitals | Wierzbicki A.S.,Guys and St Thomas Hospitals
Journal of Cardiovascular Pharmacology and Therapeutics | Year: 2013

The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia - the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented. © The Author(s) 2013.


Taylor K.M.,Guys And St Thomas Hospitals | Irving P.M.,Guys And St Thomas Hospitals
Nature Reviews Gastroenterology and Hepatology | Year: 2011

The majority of patients with IBD use conventional therapy (namely, aminosalicylates, antibiotics, corticosteroids and immunomodulatory agents) for prolonged periods of time, to both induce and maintain remission. Treatment paradigms in IBD have evolved towards a rapid escalation of therapy to achieve stringent goals, including mucosal healing and a reduction in the need for hospital admission and surgery. In this context, the failure to optimize conventional therapy can lead to a potentially effective treatment being abandoned too early, which is undesirable when only a limited number of drugs are effective in the management of IBD, and could also lead to patients being unnecessarily exposed to potentially toxic and/or expensive biologic drugs. This Review provides an overview of the many ways in which conventional therapy can be optimized, and describes strategies to improve adherence to drug regimens, such as simplifying the dosing regimen, optimizing drug delivery and dose, and tailoring medication on the basis of metabolite levels. © 2011 Macmillan Publishers Limited. All rights reserved.


Objective: To evaluate the effect of a physical training program in combination with ergonomic changes in a group of keyboard operators with nonspecific/type II work-related upper limb disorder (WRULD). Design: Prospective study. Setting: Hospital department. Participants: Pain-free controls (n=6) and currently working patients with WRULD (n=17) were included. Interventions: Participants were taught how to self-rehabilitate according to a previously published physical exercise program, in addition the patients requested maximal ergonomic assistance from their employer according to British law. Main Outcomes Measures: Pain at rest and after a standardized functional typing test, before and after rehabilitation, with recording of endurance and calculation of typing speed during the tests. Statistical evaluation: Student t test, paired, and 2-tailed. Results: After the rehabilitation program, the patients as a group had significantly less pain both at rest (P=.009) and after the typing test (P<.001). The typing endurance improved significantly (P=.027) and became similar to the healthy control group (P =.09). The typing speed improved significantly in the patient group after rehabilitation (P=.032) and became similar to the normal control group (P=.058). Conclusions: Currently working keyboard operators with nonspecific/type II WRULD can benefit significantly from a combination of an individualized self-administered physical rehabilitation program and ergonomic work place improvements. Randomized control studies are needed to further investigate the long-term effect of this encouraging finding. © 2012 by the American Congress of Rehabilitation Medicine.


Gibson T.J.,Guys and St Thomas Hospitals
Current Opinion in Rheumatology | Year: 2013

PURPOSE OF REVIEW: Gout is increasing worldwide. An appreciation that hyperuricaemia and gout are associated with hypertension and chronic kidney disease is well established, but the cause and effect relationships are controversial. Studies which address this conundrum have been reviewed. RECENT FINDINGS: Epidemiological surveys have confirmed the strong relationship of gout and hyperuricaemia with hypertension and diuretic treatment. There are multiple confounders such as obesity and alcohol consumption which despite adjustments make interpretation of the epidemiology difficult. There are data to suggest that hyperuricaemia itself causes hypertension and renovascular disease, and that lowering of serum urate may assist in control of hypertension. The mechanism for diuretic-induced hyperuricaemia may operate through volume depletion and reduced secretion of uric acid. The latter effect may be genetically influenced. SUMMARY: Recent population surveys have strongly supported the association of gout and hyperuricaemia with hypertension. The prevailing explanation that renal dysfunction causes both phenomena or that they are caused by shared factors is challenged by the evidence that hyperuricaemia drives hypertension. A confounder of epidemiology studies is the use of diuretics for treating hypertension. A closer understanding of the mechanisms of diuretic-induced hyperuricaemia may lead to the creation of uricosuric diuretics. Losartan is exceptional amongst antihypertensive drugs in possessing mild uricosuric properties and therefore has a role in treating hypertensive patients with gout. Overcoming diuretic-induced hyperuricaemia is difficult and there is need for a uricosuric diuretic. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.

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