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Langley R.E.,MRC Clinical Trials Unit | Langley R.E.,University of Sussex | Cafferty F.H.,MRC Clinical Trials Unit | Alhasso A.A.,Beatson West of Scotland Cancer Center | And 10 more authors.
The Lancet Oncology | Year: 2013

Background: Luteinising-hormone-releasing-hormone agonists (LHRHa) to treat prostate cancer are associated with long-term toxic effects, including osteoporosis. Use of parenteral oestrogen could avoid the long-term complications associated with LHRHa and the thromboembolic complications associated with oral oestrogen. Methods: In this multicentre, open-label, randomised, phase 2 trial, we enrolled men with locally advanced or metastatic prostate cancer scheduled to start indefinite hormone therapy. Randomisation was by minimisation, in a 2:1 ratio, to four self-administered oestrogen patches (100 μg per 24 h) changed twice weekly or LHRHa given according to local practice. After castrate testosterone concentrations were reached (1·7 nmol/L or lower) men received three oestrogen patches changed twice weekly. The primary outcome, cardiovascular morbidity and mortality, was analysed by modified intention to treat and by therapy at the time of the event to account for treatment crossover in cases of disease progression. This study is registered with ClinicalTrials.gov, number NCT00303784. Findings: 85 patients were randomly assigned to receive LHRHa and 169 to receive oestrogen patches. All 85 patients started LHRHa, and 168 started oestrogen patches. At 3 months, 70 (93%) of 75 receiving LHRHa and 111 (92%) of 121 receiving oestrogen had achieved castrate testosterone concentrations. After a median follow-up of 19 months (IQR 12-31), 24 cardiovascular events were reported, six events in six (7·1%) men in the LHRHa group (95% CI 2·7-14·9) and 18 events in 17 (10·1%) men in the oestrogen-patch group (6·0-15·6). Nine (50%) of 18 events in the oestrogen group occurred after crossover to LHRHa. Mean 12-month changes in fasting glucose concentrations were 0·33 mmol/L (5·5%) in the LHRHa group and -0·16 mmol/L (-2·4%) in the oestrogen-patch group (p=0·004), and for fasting cholesterol were 0·20 mmol/L (4·1%) and -0·23 mmol/L (-3·3%), respectively (p<0·0001). Other adverse events reported by 6 months included gynaecomastia (15 [19%] of 78 patients in the LHRHa group vs 104 [75%] of 138 in the oestrogen-patch group), hot flushes (44 [56%] vs 35 [25%]), and dermatological problems (10 [13%] vs 58 [42%]). Interpretation: Parenteral oestrogen could be a potential alternative to LHRHa in management of prostate cancer if efficacy is confirmed. On the basis of our findings, enrolment in the PATCH trial has been extended, with a primary outcome of progression-free survival. Funding: Cancer Research UK, MRC Clinical Trials Unit. © 2013 Elsevier Ltd. Source

Burbidge S.,Leeds Teaching Hospitals | Mahady K.,Leeds Teaching Hospitals | Naik K.,Mid Yorkshire NHS Trust
Clinical Radiology | Year: 2013

Aim: To assess the relative roles of computed tomography (CT) and diagnostic laparoscopy in the staging process of patients with potentially curable gastric cancer. Materials and methods: Fifty-two patients underwent laparoscopy and CT as part of staging; 36 patients underwent surgery without laparoscopy. Pathological findings at laparoscopy or surgery were compared with initial CT reports, and analysis of the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was performed. Results: Of the patients who underwent laparoscopy and CT, six were staged as positive for peritoneal disease (PD), of which five (83%) were positive for PD at laparoscopy. Forty-six patients were reported at CT as negative for PD, of which 40 (87%) were negative at laparoscopy. Of 36 patients with no advanced disease at CT, who had surgery without diagnostic laparoscopy, nine (25%) were positive at surgery for PD. The overall sensitivity of CT for PD was therefore 25%, the specificity was 99%, the PPV was 86%, and the NPV was 83%. Conclusion: CT is not sufficiently sensitive to detect or exclude PD in patients with gastric cancer, although is highly specific. Staging laparoscopy is an essential adjunct to imaging in all patients being considered for curative surgery for gastric cancer. © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Source

Sivaprasad S.,Kings College | Gupta B.,Kings College | Gulliford M.C.,Kings College London | Dodhia H.,Lambeth NHS Primary Care Trust | And 3 more authors.
PLoS ONE | Year: 2012

Aims: To compare the prevalence of diabetic retinopathy (DR) in people of various ethnic groups with diabetes in the United Kingdom (UK). Methods: The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in the study. Data included age, sex, ethnic group, type of diabetes, presenting visual acuity and the results of grading of diabetic retinopathy. Prevalence estimates for the ethnic groups were age-standardised to the white European population for comparison purposes. Results: Out of 57,144 people on the two diabetic registers, data were available on 50,285 individuals (88.0%), of these 3,323 had type 1 and 46,962 had type 2 diabetes. In type 2 diabetes, the prevalence of any DR was 38.0% (95% confidence interval(CI) 37.4% to 38.5%) in white Europeans compared to 52.4% (51.2% to 53.6%) in African/Afro-Caribbeans and 42.3% (40.3% to 44.2%) in South Asians. Similarly, sight threatening DR was also significantly more prevalent in Afro-Caribbeans (11.5%, 95% CI 10.7% to 12.3%) and South Asians (10.3%, 9.0% to 11.5%) compared to white Europeans (5.5%, 5.3% to 5.8%). Differences observed in Type 1 diabetes did not achieve conventional levels of statistical significance, but there were lower numbers for these analyses. Conclusions: Minority ethnic communities with type 2 diabetes in the UK are more prone to diabetic retinopathy, including sight-threatening retinopathy and maculopathy compared to white Europeans. © 2012 Sivaprasad et al. Source

Davey R.,Mid Yorkshire NHS Trust | Bamford J.,Leeds Teaching Hospitals NHS Trust | Emery P.,Leeds Teaching Hospitals NHS Trust
Lupus | Year: 2010

Neuropsychiatric manifestations of systemic lupus erythematosus are common and disabling yet their pathogenesis is poorly understood. We investigated the role of cerebrovascular endothelial dysfunction in systemic lupus erythematosus and its neuropsychiatric manifestations. Subjects with systemic lupus erythematosus were recruited prospectively along with matched healthy control subjects. The presence of neuropsychiatric systemic lupus erythematosus syndromes was ascertained according to standard definitions. Cerebrovascular reactivity, an indicator of endothelial function, was measured using transcranial Doppler ultrasound. Sixty-one subjects (58 female, 3 male) with systemic lupus erythematosus and 70 control subjects were assessed. Sixty patients (98%) reported at least one neuropsychiatric manifestation, the most prevalent being headache and cognitive dysfunction. There was no significant difference in cerebrovascular reactivity between cases and controls (3.06 vs 3.06, p=0.99). Subjects with systemic lupus erythematosus and a history of stroke and/or transient ischaemic attack had significantly higher cerebrovascular reactivity than those without (3.99 vs 2.79, p = 0.007). No association was found between the presence of other neuropsychiatric syndromes or systemic lupus erythematosus-related variables and altered cerebrovascular reactivity. In conclusion, cerebrovascular endothelial dysfunction is not present in the majority of subjects with systemic lupus erythematosus. However, the role of endothelial dysfunction in the pathogenesis of stroke and transient ischaemic attack in systemic lupus erythematosus merits further investigation. © 2010 The Author(s). Source

Naredo E.,Complutense University of Madrid | D'Agostino M.A.,University of Versailles | Wakefield R.J.,University of Leeds | Moller I.,Instituto Poal Of Reumatologia | And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). Methods We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's ê. Interobserver reliability was assessed by Light's ê. Weighted ê coefficients with absolute weighting were computed for B-mode and PD signal. Results Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (ê value 0.72 for B-mode; ê value 0.78 for PD mode). Interobserver reliability assessment showed good ê values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate ê values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). Conclusions US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA. Source

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