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Lincoln, United Kingdom

James N.D.,University of Birmingham | Hussain S.A.,University of Birmingham | Hussain S.A.,University of Liverpool | Hall E.,Institute of Cancer Research | And 10 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND:Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone. METHODS:In this multicenter, phase 3 trial, we randomly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of body-surface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volume of bladder receiving full-dose radiotherapy was reduced) in a partial 2-by-2 factorial design (results not reported here). The primary end point was survival free of locoregional disease. Secondary end points included overall survival and toxic effects. RESULTS:At 2 years, rates of locoregional disease-free survival were 67% (95% confidence interval [CI], 59 to 74) in the chemoradiotherapy group and 54% (95% CI, 46 to 62) in the radiotherapy group. With a median follow-up of 69.9 months, the hazard ratio in the chemoradiotherapy group was 0.68 (95% CI, 0.48 to 0.96; P = 0.03). Five-year rates of overall survival were 48% (95% CI, 40 to 55) in the chemoradiotherapy group and 35% (95% CI, 28 to 43) in the radiotherapy group (hazard ratio, 0.82; 95% CI, 0.63 to 1.09; P = 0.16). Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment (36.0% vs. 27.5%, P = 0.07) but not during follow-up (8.3% vs. 15.7%, P = 0.07). CONCLUSIONS:Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events. (Funded by Cancer Research U.K.; BC2001 Current Controlled Trials number, ISRCTN68324339.). Copyright © 2012 Massachusetts Medical Society. Source

Dudley N.J.,United Lincolnshire Hospitals NHS Trust | Gibson N.M.,University of Nottingham
Ultrasound | Year: 2014

Ultrasound scanner preset programmes are factory set or tailored to user requirements. Scanners may, therefore, have different settings for the same application, even on similar equipment in a single department. The aims of this study were: (1) to attempt to match the performance of two scanners, where one was preferred and (2) to assess differences between six scanners used for breast ultrasound within our organisation. The Nottingham Ultrasound Quality Assurance software was used to compare imaging performance. Images of a Gammex RMI 404GS test object were collected from six scanners, using default presets, factory presets and settings matched to a preferred scanner. Resolution, low contrast performance and high contrast performance were measured. The performance of two scanners was successfully matched, where one had been preferred. Default presets varied across the six scanners, three different presets being used. The most used preset differed in settings across the scanners, most notably in the use of different frequency modes. The factory preset was more consistent across the scanners, the main variation being in dynamic range (55-70 dB). Image comparisons showed significant differences, which were reduced or eliminated by adjustment of settings to match a reference scanner. It is possible to match scanner performance using the Nottingham Ultrasound Quality Assurance software as a verification tool. Ultrasound users should be aware that scanners may not behave in a similar fashion, even with apparently equivalent presets. It should be possible to harmonise presets by consensus amongst users. Source

Sreedharan A.,United Lincolnshire Hospitals NHS Trust
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: There is conflicting evidence regarding the clinical efficacy of proton pump inhibitors (PPI) initiated before endoscopy for upper gastrointestinal bleeding. OBJECTIVES: To systematically review evidence from randomised controlled trials (RCTs) of PPI treatment initiated before endoscopy for upper gastrointestinal bleeding. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE and CINAHL databases and major conference proceedings to September 2005, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model. Searches were re-run in February 2006 and October 2008. SELECTION CRITERIA: We selected randomised controlled trials (RCTs), of hospitalised participants with unselected upper gastrointestinal bleeding, undergoing active treatment with a proton pump inhibitor PPI (oral or intravenous) and control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment prior to endoscopy. Outcomes were assessed at 30 days and included mortality, rebleeding and surgery. Also assessed were stigmata of recent haemorrhage (SRH; active bleeding, non bleeding visible vessel or adherent clot) at index endoscopy, length of hospital stay, blood transfusion requirements and requirement for endoscopic therapy at index endoscopy. DATA COLLECTION AND ANALYSIS: At least two review authors assessed eligibility criteria and extracted data regarding outcomes and factors affecting methodological quality. MAIN RESULTS: Six RCTs comprising 2223 participants were included. There was no statistical heterogeneity among trials for dichotomous outcomes. There were no statistically significant differences in mortality, rebleeding or surgery between PPI and control treatment. Unweighted pooled mortality rates were 6.1% and 5.5% respectively (odds ratio (OR)1.12; 95% CI 0.72 to 1.73). Unweighted pooled rebleeding rates were 13.9% and 16.6% respectively (OR 0.81; 95%CI 0.61 to 1.09). Pooled rates for surgery were 9.9% and 10.2% respectively (OR 0.96 95% CI 0.68 to 1.35). PPI treatment compared to control significantly reduced the proportion of participants with SRH at index endoscopy; unweighted pooled rates were 37.2% and 46.5% respectively (OR 0.67; 95% CI 0.54 to 0.84). However, this result was not robust to sensitivity analysis. PPI treatment compared to control significantly reduced endoscopic therapy at index endoscopy; unweighted pooled rates were 8.6% and 11.7% respectively (OR 0.68; 95% CI 0.50 to 0.93). For continuous outcomes (length of hospital stay and blood transfusion requirements), quantitative analysis could not be performed. AUTHORS' CONCLUSIONS: PPI treatment initiated before endoscopy for upper gastrointestinal bleeding might reduce the proportion of participants with SRH at index endoscopy and significantly reduces requirement for endoscopic therapy during index endoscopy. However, there is no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding or need for surgery. Source

Dudley N.J.,United Lincolnshire Hospitals NHS Trust
Ultrasound | Year: 2013

Estimated fetal weight is used in fetal growth monitoring and, if accurately estimated, may provide a sensitive screening tool for the small-for-gestational-age fetus, which may then proceed to further investigations. There is considerable evidence, however, that ultrasound-estimated fetal weight is inaccurate. The aim of this study was to review the literature on the efficacy of estimated fetal weight in the early prediction of low birthweight. Seven studies met the inclusion criteria. Most studies used an estimated fetal weight threshold of the 10th percentile, where sensitivity for predicting small-for-gestational-age infants in low-risk groups is low and specificity is high. The sensitivity of estimated fetal weight is higher where the prevalence of small-for-gestational-age is higher or a higher detection threshold is used. Fetal weight estimation is more sensitive and specific than other measures in detecting small-for-gestational-age, but is limited by large random errors. Random errors reduce sensitivity with less effect on specificity. High sensitivity is useful where further discriminatory tests are available; this may be the case here, where Doppler ultrasound is of proven value in high-risk groups. High specificity is required where invasive or expensive procedures will be performed on the selected group. In order to achieve sensitivity approaching 100%, a threshold 3 standard deviations of estimated fetal weight error above the 10th percentile of fetal weight is required. Smaller random errors will allow the threshold to be reduced and will increase specificity. Source

Armstrong R.G.,United Lincolnshire Hospitals NHS Trust | West J.,University of Nottingham | Card T.R.,University of Nottingham
American Journal of Gastroenterology | Year: 2010

OBJECTIVES: Azathioprine is an accepted treatment of inflammatory bowel disease (IBD), but concerns exist regarding its carcinogenic potential. Studies in renal transplant and rheumatology patients have reported an increased cancer risk. In IBD, studies suggest a small increased risk of lymphoma and protection against colorectal cancer, but the overall risk of malignancy has not been established. METHODS: We conducted a nested case-control study using the General Practice Research Database. Records of IBD patients were examined for azathioprine prescriptions and cancers. Prescriptions per year of follow-up were grouped for analysis. Azathioprine use was compared between IBD cases (with a diagnosed cancer) and IBD controls (without). Results: Overall, 15,471 patients with IBD and over 1 year of appropriate data were identified. Among these, 392 developed cancer, of whom 10.5% received at least one prescription for azathioprine, compared with 1,914 (12.7%) of the controls. Analyzing the occurrence of any cancer against azathioprine prescription showed a nonsignificant protective effect (odds ratio (OR)0.92, 95% confidence interval (CI)=0.79-1.06). Correction for the effects of age and smoking removed this effect (OR=1.04, 95% CI=0.89-1.21). Diagnosis of lymphoma was associated with ever use of azathioprine with OR of 3.22, CI=1.01-10.18. Conclusions: We found evidence of an increased risk of lymphoma, which is consistent with previous studies. We found no overall increase in risk of cancer in individuals with IBD who had taken azathioprine. Our study does not show a need for azathioprine cessation in the medium term in IBD because of the risk of malignancy. © 2010 by the American College of Gastroenterology. Source

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