INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): Study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing
Murdoch M.,Royal Infirmary |
McColl E.,Northumbria University |
Howel D.,Northumbria University |
Deverill M.,Northumbria University |
And 9 more authors.
Trials | Year: 2011
Background: Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness.The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness.Methods/design: This is a mixed methods pragmatic multicentre feasibility pilot study with four components:-. (a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial.(b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience.(c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial.(d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions.Discussion: The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim.Trial registration number: Current Controlled Trials ISRCTN71327395 assigned 7thJune 2010. © 2011 Murdoch et al; licensee BioMed Central Ltd.
Hadjivassiliou M.,The Royal Hallamshire Hospital
Handbook of Clinical Neurology | Year: 2011
The cerebellum, and in particular the Purkinje cells within it, appear to be a frequent immunological target in the context of some systemic diseases. This is perhaps more often the case with the cerebellum by comparison to other structures within the central nervous system. This observation may relate to the fact that the cerebellum is one of the largest, oldest, and most structurally conserved structures in the vertebrate nervous system and/or that Purkinje cells possess good and multiple antigenic targets. Immune-mediated ataxias include paraneoplastic cerebellar degeneration and post-infective cerebellitis, but these will be discussed elsewhere. This chapter covers in detail the epidemiology, clinical characteristics, pathophysiology, and treatment of some other examples of immune-mediated ataxias, including gluten ataxia and ataxia associated with anti-GAD antibodies. There is particular emphasis on gluten ataxia as this is one of the commonest immune-mediated cerebellar ataxias and one of the few ataxias that are potentially treatable. The chapter also introduces the concept of primary autoimmune cerebellar ataxia as a form of organ-specific autoimmune disease for the first time. The pathophysiology leading to cerebellar damage, loss of Purkinje cells, and the development of ataxia remains speculative, but existing clues are discussed in detail. © 2012 Elsevier B.V.
Sydes M.R.,MRC Clinical Trials Unit |
Parmar M.K.B.,MRC Clinical Trials Unit |
Mason M.D.,University of Cardiff |
Clarke N.W.,The Christie and Salford Royal Hospitals Foundations Trusts |
And 12 more authors.
Trials | Year: 2012
Background: Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial.Methods: STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate 'activity' stages (focus: failure-free survival), and a final 'efficacy' stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims.Results: (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design.(2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies.Conclusions: The STAMPEDE experience shows that recruitment to a MAMS trial and mid-flow changes its design are achievable with good planning. This benefits patients and the scientific community as research treatments are evaluated in a more efficient and cost-effective manner.Trial registration: ISRCTN78818544, NCT00268476. First patient into trial: 17 October 2005. First patient into abiraterone comparison: 15 November 2011. © 2012 Sydes et al.; licensee BioMed Central Ltd.
Ganeshan A.,John Radcliffe Hospital |
Nazir S.A.,John Radcliffe Hospital |
Hon L.Q.,The Royal Hallamshire Hospital |
Upponi S.S.,John Radcliffe Hospital |
And 3 more authors.
European Journal of Radiology | Year: 2010
Interventional radiology is continuing to reshape current practice in many specialties of clinical care. It is a relatively new and innovative branch of medicine in which physicians treat diseases non-operatively through small catheters guided to the target by fluoroscopic and other imaging modalities. The aim is to provide image-guided, minimally invasive alternatives to traditional surgical and medical procedures in suitable cohorts of patients. Procedures which previously required major surgery can now be performed by interventional radiologists, sometimes on an outpatient basis, with little patient discomfort. In this review, we highlight the importance of interventional radiology in treating a comprehensive range of obstetric and gynaecological pathologies. © 2009 Elsevier Ireland Ltd. All rights reserved.
While B.,The Royal Hallamshire Hospital |
Mudhar H.S.,National Specialist Ophthalmic Pathology Service NSOPS |
Chan J.,The Royal Hallamshire Hospital
European Journal of Ophthalmology | Year: 2013
To present a case of lens particle glaucoma in a child with an untreated unilateral congenital cataract and persistent fetal vasculature (PFV) and to discuss the implications for the management of unilateral congenital cataract. Methods. A 4-year-old boy presented with a unilateral congenital cataract affecting the right eye. Examination revealed a cataract and PFV. Intraocular pressure (IOP) measured 18 mmHg right, 14 mmHg left, and he was managed conservatively. Nine months later, he attended clinic with a painful right eye. He had quiet anterior and posterior segments but free lens particles in the anterior vitreous and an IOP of 12 mmHg. Over 4 weeks, the IOP rose to 23 mmHg and the patient underwent vitreolensectomy. Results. The affected eye has at no point become inflamed but macrophages laden with lens proteins were identified during histopathologic analysis of the vitreous. The proposed mechanism in this case is that the PFV weakened the posterior capsule leading to its rupture. The resultant macrophages then caused mechanical obstruction of aqueous outflow through the trabecular meshwork. Conclusions. Lens particle glaucoma secondary to posterior capsular rupture is a rare form of lensinduced glaucoma. It is common practice to manage conservatively those patients who present late with unilateral congenital cataract. This case highlights the need for vigilant follow-up of these patients to enable lens-induced glaucoma to be detected at an early stage. © 2012 Wichtig Editore.