Mikhail A.,Morriston Hospital |
Advances in Therapy | Year: 2013
Biosimilars have been developed for several biologic therapeutic agents, including erythropoiesis-stimulating agents (ESAs). However, biosimilars cannot be assumed to be completely identical to the reference product, nor can two different biosimilars of the same reference product be considered equivalent. Accordingly, standards for approving biosimilars are distinct from those for generic versions of conventional pharmaceuticals. By late 2007, two biosimilar epoetins (HX575 and SB309) had been approved by the European Medicines Agency (EMA), following a series of pharmacokinetic and pharmacodynamic equivalence studies, as well as phase 3 clinical comparability evaluations. Additionally, the results of a limited number of postauthorization interventional or observational studies and quality comparisons were published subsequently on both products. The reported differences in glycosylation profiles between these epoetin biosimilars and their reference product, as well as the lack of long-term safety and efficacy evaluation, could indicate a need to develop a more comprehensive analysis of the available data, and to evaluate the post-authorization real-life data, in order to gain a better understanding of any potential implications of molecular structural or formulation differences on longterm safety and effectiveness. Switching between an original reference ESA and a biosimilar (and possibly also switching between biosimilar versions of the same product) should be regarded as a change in clinical management. Clinicians need to be fully involved in such decisions. Prescribing by brand name will prevent unintentional substitution by pharmacists and allow for effective pharmacovigilance, in accordance with recent EU directives. In this review, the authors have analyzed most of the published information on the two epoetin biosimilars, HX575 and SB309, to highlight the points that healthcare providers may need to consider when assessing an epoetin biosimilar. © The Author(s) 2012. This article is published with open access at Springerlink.com.
Wald D.S.,Queen Mary, University of London |
Wald D.S.,London Chest Hospital |
Morris J.K.,Queen Mary, University of London |
Wald N.J.,Queen Mary, University of London |
And 5 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: In acute ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to treat the artery responsible for the infarct (infarct, or culprit, artery) improves prognosis. The value of PCI in noninfarct coronary arteries with major stenoses (preventive PCI) is unknown. METHODS: From 2008 through 2013, at five centers in the United Kingdom, we enrolled 465 patients with acute STEMI (including 3 patients with left bundle-branch block) who were undergoing infarct-artery PCI and randomly assigned them to either preventive PCI (234 patients) or no preventive PCI (231 patients). Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia. The primary outcome was a composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina. An intention-to-treat analysis was used. RESULTS: By January 2013, the results were considered conclusive by the data and safety monitoring committee, which recommended that the trial be stopped early. During a mean follow-up of 23 months, the primary outcome occurred in 21 patients assigned to preventive PCI and in 53 patients assigned to no preventive PCI (infarct-artery- only PCI), which translated into rates of 9 events per 100 patients and 23 per 100, respectively (hazard ratio in the preventive-PCI group, 0.35; 95% confidence interval [CI], 0.21 to 0.58; P<0.001). Hazard ratios for the three components of the primary outcome were 0.34 (95% CI, 0.11 to 1.08) for death from cardiac causes, 0.32 (95% CI, 0.13 to 0.75) for nonfatal myocardial infarction, and 0.35 (95% CI, 0.18 to 0.69) for refractory angina. CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease undergoing infarctartery PCI, preventive PCI in noninfarct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events, as compared with PCI limited to the infarct artery. Copyright © 2013 Massachusetts Medical Society.
Azzopardi E.A.,University of Cardiff |
Azzopardi E.A.,Morriston Hospital |
Ferguson E.L.,University of Cardiff |
Thomas D.W.,University of Cardiff
Journal of Antimicrobial Chemotherapy | Year: 2013
Multidrug-resistant, Gram-negative infection is a major global determinant of morbidity, mortality and cost of care. The advent of nanomedicine has enabled tailored engineering of macromolecular constructs, permitting increasingly selective targeting, alteration of volume of distribution and activity/toxicity. Macromolecules tend to passively and preferentially accumulate at sites of enhanced vascular permeability and are then retained. This enhanced permeability and retention (EPR) effect, whilst recognized as a major breakthrough in anti-tumoral targeting, has not yet been fully exploited in infection. Shared pathophysiological pathways in both cancer and infection are evident and a number of novel nanomedicines have shown promise in selective, passive, size-mediated targeting to infection. This review describes the similarities and parallels in pathophysiological pathways at molecular, cellular and circulatory levels between inflammation/infection and cancer therapy, where use of this principle has been established. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Davies A.P.,Morriston Hospital
Knee | Year: 2013
Background: Unicompartmental patellofemoral arthroplasties are uncommon however numbers are increasing and there are a variety of new prostheses available. The Femoro-Patella Vialla (FPV, Wright Medical) device was the second most commonly used patellofemoral unicompartmental prosthesis in the 2012 British National Joint Register. There are however no published outcomes data for this device. Method: 52 consecutive cases were studied prospectively using Oxford Knee Score and American Knee Society Scores pre-operatively and at follow up to a minimum of two years. Results: Overall Oxford Knee Scores improved from 30 points pre-operatively (36.6%) to 19 points (60%) at one-year. American Knee Society Knee scores improved from 51 points pre-operatively to 81 points at one-year. Function scores improved from 42 points pre-operatively to 70 points at one-year. 13 (25%) patients had an excellent outcome with pain abolished and near normal knee function. 11 (21%) patients gained very little improvement and scored their knees similar or worse to their pre-operative state. There were no infective or thromboembolic complications. Seven cases have been revised to a total knee replacement for on-going pain in six cases and progression of arthritis in the tibio-femoral compartments in one case. The patellar button was found to be very poorly fixed in all cases that were revised. Conclusion: Early results with the FPV prosthesis demonstrate that successful outcomes can be achieved however the results were unpredictable and a significant minority of patients had on-going symptoms that they found unacceptable. The early revision rate was high in this series. © 2013 Elsevier B.V.
Mowbray N.G.,Morriston Hospital
Pancreas | Year: 2016
OBJECTIVES: Laparoscopic techniques have been slow to establish a role in pancreatic surgery. Worldwide, laparoscopic left pancreatectomy (LLP) is gaining in popularity; however, there remains little published data from the United Kingdom.We aimed to evaluate the results of LLP performed in a single UK pancreatic unit. METHODS: Patients undergoing LLP for lesions in the body and tail of the pancreas between April 2009 and April 2015 were identified. Patient records were reviewed retrospectively. RESULTS: Laparoscopic left pancreatectomy was performed on 46 patients, median age, 62 years (range, 19-84). The spleen was preserved in 27 patients (93% of planned), and 6 (13%) operations were converted to open. The overall morbidity rate was 39%; 28 patients had no complications. Significant complications were seen in 7 (15%) patients; this included 3 pancreatic fistula (6.5%) and 1 mortality (2%). Median length of stay was 6 days (range, 3-28). Histology revealed 15 neuroendocrine tumors, 8 adenocarcinomas, 4 mucinous cystadenomas, 1 intraductal papillary mucinous neoplasm, 2 metastases, and 16 other benign pathologies. CONCLUSIONS: Laparoscopic pancreatic surgery has a low risk of significant complications. Our results offer encouragement to identify LLP as the gold standard approach for premalignant lesions. Further work should clarify the outcomes for malignant lesions. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Gurzun M.-M.,Morriston Hospital |
Ionescu A.,Morriston Hospital
European Heart Journal Cardiovascular Imaging | Year: 2014
BackgroundAppropriateness of use criteria (AUC) for transthoracic echocardiography (TTE) have been developed by American cardiology associations to help avoid unnecessary scans by formalizing indications for imaging. There are 98 indications classified as either appropriate (A), inappropriate (I), or uncertain (U). AUC may allow better targeting of limited resources, but they have not been tested systematically outside the USA.Aim of the studyTo test AUC in Wales, one of the four countries of the UK.MethodsWe collected requests for TTE and the corresponding TTE reports from all Welsh hospitals during 1 week in June 2012 and analysed them according to appropriateness, specialty, and location (secondary vs. tertiary services) of the referring physician.ResultsWe analysed 1070 pairs of echocardiography requests and TTE reports from 14 hospitals [mean age 66.5 (16.1) years; 579 (51%) M]: A - 922 (86%); I - 115 (11%), and U - 33 (3%); 287 (25%) studies were from two tertiary centres and 338 (29.5%) were of inpatients. Main indications were the evaluation of: cardiac structure and function (489, 45.7%), valvular function (267, 25%), and hypertension, heart failure, or cardiomyopathy (149, 13.9%). In-patient requests (main indication - 'initial evaluation of left ventricle ejection fraction post acute coronary syndrome' - 44 studies, 13.7%) were more often appropriate than outpatients (main indication - 'symptoms/conditions potentially related to suspected cardiac aetiology' - 142 studies, 19.8%): 94.4 vs. 83.5%, P < 0.05. The most common inappropriate indication was 'initial evaluation for a murmur/click without symptoms/signs of structural heart disease' (29 studies, 2.7%). The proportion of appropriate requests by specialty was 89% for medical, 87% for GPs, 85.3% for cardiologists, 80.8% for surgical, and 60% for cardiac surgeons (P < 0.05 for cardiac surgeons); 47.8% of requests were generated by cardiologists, and abnormalities were detected in 82% of all scans (37% minor findings and 45% major findings), least often in those requested by general practitioners.ConclusionApplication of AUC yields results similar to those reported from the USA; ∼1 in 10 scans could be avoided. © The Author 2013.
Nambiar A.,Morriston Hospital |
Cody J.D.,Morriston Hospital |
Jeffery S.T.,Morriston Hospital
The Cochrane database of systematic reviews | Year: 2014
BACKGROUND: Urinary incontinence has been shown to affect up to 50% of women. Studies in the United States have shown that up to 80% of these women have an element of stress urinary incontinence. Colposuspension and now mid-urethral slings have been shown to be effective in treating patients with stress incontinence. However, associated adverse events include bladder and bowel injury, groin pain and haematoma formation. This has led to the development of third-generation single-incision slings, also referred to as mini-slings.It should be noted that TVT-Secur (Gynecare, Bridgewater, NJ, USA) is one type of single-incision sling; it has been withdrawn from the market because of poor results. However, it is one of the most widely studied single-incision slings and was used in several of the trials included in this review. Despite its withdrawal from clinical use, it was decided that data pertaining to this sling should be included in the first iteration of this review, so that level 1a data are available in the literature to confirm its lack of efficacy.OBJECTIVES: To assess the effectiveness of mini-sling procedures in women with urodynamic clinical stress or mixed urinary incontinence in terms of improved continence status, quality of life or adverse events.SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE in process; we handsearched journals and conference proceedings (searched 6 February 2013) and searched ClinicalTrials.gov (searched 20 September 2012), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (searched 20 September 2012) and the reference lists of relevant articles.SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with urodynamic stress incontinence, symptoms of stress incontinence or stress-predominant mixed urinary incontinence, in which at least one trial arm involves one of the new single-incision slings. The definition of a single-incision sling is "a sling that does not involve either a retropubic or transobturator passage of the tape or trocar and involves only a single vaginal incision (i.e. no exit wounds in the groin or lower abdomen)."DATA COLLECTION AND ANALYSIS: Three review authors assessed the methodological quality of potentially eligible trials and independently extracted data from the individual trials.MAIN RESULTS: We identified 31 trials involving 3290 women. Some methodological flaws were observed in some trials; a summary of these is given in the 'Risk of bias in included studies' section.No studies compared single-incision slings versus no treatment, conservative treatment, colposuspension, laparoscopic procedures or traditional sub-urethral slings. Also no data on the comparison of single-incision slings versus retropubic mid-urethral slings (top-down approach) were available, but the review authors believe this did not affect the overall comparison versus retropubic mid-urethral slings.The types of single-incision slings included in this review were TVT-Secur (Gynecare), MiniArc (American Medical Systems, Minnetonka, MN, USA), Ajust (C.R. Bard, Inc.,Covington, GA, USA), Needleless (Mayumana Healthcare, Lisse, The Netherlands), Ophira (Promedon, Cordoba, Argentina), Tissue Fixation System (TFS PTY Ltd, Sydney, Australia) and CureMesh (D.Med. Co., Inc., Seoul, Korea).Women were more likely to remain incontinent after surgery with single-incision slings than with retropubic slings such as tension-free vaginal tape (TVT(TM)) (121/292, 41% vs 72/281, 26%; risk ratio (RR) 2.08, 95% confidence interval (CI) 1.04 to 4.14). Duration of the operation was slightly shorter for single-incision slings but with higher risk of de novo urgency (RR 2.39, 95% CI 1.25 to 4.56). Four of five studies in the comparison included TVT-Secur as the single-incision sling.Single-incision slings resulted in higher incontinence rates compared with inside-out transobturator slings (30% vs 11%; RR 2.55, 95% CI 1.93 to 3.36). The adverse event profile was significantly worse, specifically consisting of higher risks of vaginal mesh exposure (RR 3.75, 95% CI 1.42 to 9.86), bladder/urethral erosion (RR 17.79, 95% CI 1.06 to 298.88) and operative blood loss (mean difference 18.79, 95% CI 3.70 to 33.88). Postoperative pain was less common with single-incision slings (RR 0.29, 95% CI 0.20 to 0.43), and rates of long-term pain or discomfort were marginally lower, but the clinical significance of these differences is questionable. Most of these findings were derived from the trials involving TVT-Secur: Excluding the other trials showed that high risk of incontinence was principally associated with use of this device (RR 2.65, 95% CI 1.98 to 3.54). It has been withdrawn from clinical use.Evidence was insufficient to reveal a difference in incontinence rates with other single-incision slings compared with inside-out or outside-in transobturator slings. Duration of the operation was marginally shorter for single-incision slings compared with transobturator slings, but only by approximately two minutes and with significant heterogeneity in the comparison. Risks of postoperative and long-term groin/thigh pain were slightly lower with single-incision slings, but overall evidence was insufficient to suggest a significant difference in the adverse event profile for single-incision slings compared with transobturator slings. Evidence was also insufficient to permit a meaningful sensitivity analysis of the other single-incision slings compared with transobturator slings, as all confidence intervals were wide. The only significant differences were observed in rates of postoperative and long-term pain, and in duration of the operation, which marginally favoured single-incision slings.Overall results show that TVT-Secur is considerably inferior to retropubic and inside-out transobturator slings, but additional evidence is required to allow any reasonable comparison of other single-incision slings versus transobturator slings.When one single-incision sling was compared with another, evidence was insufficient to suggest a significant difference between any of the slings in any of the comparisons made.AUTHORS' CONCLUSIONS: TVT-Secur is inferior to standard mid-urethral slings for the treatment of women with stress incontinence and has already been withdrawn from clinical use. Not enough evidence has been found on other single-incision slings compared with retropubic or transobturator slings to allow reliable comparisons. Additional adequately powered and high-quality trials with longer-term follow-up are required. Trials should clearly describe the fixation mechanism of these single-incisions slings: It is apparent that, although clubbed together as a single group, a significant difference in fixation mechanisms may influence outcomes.
Ricks R.,Morriston Hospital
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2010
Tungsten carbide (WC) is an incredibly hard inorganic compound that has recently become fashionable in the manufacture of men's jewellery, particularly wedding rings. It is a common misconception that these rings are unable to be cut and emergency treatment to remove them necessitates the amputation of the finger trapped within. We present a case of such a ring being successfully removed with the use of a diamond tipped dental drill with restoration of function and preservation of the finger. This is a previously undocumented method of removal of this type of ring in the English language literature. © 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Nambiar A.,Morriston Hospital |
Lucas M.,Morriston Hospital
Neurourology and Urodynamics | Year: 2014
This chapter focuses on the position of botulinum toxin type A in the treatment pathway for overactive bladder (OAB) and neurogenic lower urinary tract dysfunction associated with neurogenic detrusor overactivity (NDO), and the recommendations of the major international guideline groups. Recommendations of different guideline groups may vary, especially when evidence is weak, often because of differences in methodology and panel composition. Relevant guidelines from the European Association of Urology, American Urological Association, and the UK National Institute for Care and Clinical Excellence were reviewed, and the recommendations that form the basis of the treatment algorithms have been discussed. Any differences between guidelines have been highlighted and special emphasis made on the position of botulinum toxin type A in these pathways. In all the reviewed guidelines, botulinum toxin type A is recommended, alongside sacral nerve neuromodulation, to treat OAB and NDO in patients who have failed oral therapy. The evidence base is consistent, but further evidence is required regarding optimal dosing regimens and injection technique. © 2014 Wiley Periodicals, Inc.
George S.C.,Morriston Hospital |
Boyce D.E.,Morriston Hospital
Plastic and Reconstructive Surgery | Year: 2014
BACKGROUND:: When is common peroneal nerve repair worthwhile? What is the effect of delayed repair? What is the maximum length of graft that can be used? This study aimed to address these questions by assessing the current literature and ascertaining the predictors of outcome that would guide peripheral nerve surgeons in determining the correct treatment of common peroneal nerve injury. METHODS:: After an extensive literature review, 28 studies (1577 repairs) were assessed. The authors evaluated outcomes, using the British Medical Research Council grading for motor recovery, where M4 or above was considered a good outcome, and related them to delay, graft length, mechanism of injury, and age. RESULTS:: Good outcomes (M4 and M5) were obtained in 45 percent of cases; more specifically, 80 percent for neurolysis, 37 percent for direct suture, and 36 percent for nerve graft. Excluding neurolysis, good outcomes were obtained in 44 percent of repairs performed within 6 months but in only 12 percent of repairs performed after 12 months (p = 0.0046), and in 64 percent of repairs using grafts shorter than 6 cm but in only 11 percent of repairs using grafts longer than 12 cm (p = 0.0002). Age did not influence outcome (p = 0.2750). CONCLUSIONS:: Common peroneal nerve repair was worthwhile in approximately half of all cases. The authors suggest that the results of common peroneal nerve repair will be suboptimal if surgery is performed more than 12 months after injury or if a graft of more than 12 cm is required. © 2014 by the American Society of Plastic Surgeons.