Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer [Vergleich der Morbidität und Tumorkontrolle nach Behandlung des Prostatakarzinoms mit dreidimensionaler konformaler (3D-CRT 70/74 Gy) und intensitätsmodulierter Strahlentherapie (IMRT 78/82 Gy)]
Dolezel M.,Multiscan Pardubice Regional Hospital |
Dolezel M.,Charles University |
Odrazka K.,Multiscan Pardubice Regional Hospital |
Odrazka K.,Charles University |
And 8 more authors.
Strahlentherapie und Onkologie | Year: 2015
Purpose: The purpose of this work was to compare toxicity and cancer control between patients with prostate cancer treated using three-dimensional conformal radiotherapy (3D-CRT) and those treated using intensity-modulated radiation therapy (IMRT). Methods and materials: A total of 553 patients with prostate cancer were treated with 3D-CRT 70–74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78–82 Gy (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT criteria. Biochemical failure was defined using the Phoenix and ASTRO definitions. Results: The 5-year risk of grade 2–4 genitourinary toxicity was 26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB 82) without statistical differences. The 5-year risk of grade 2–4 gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 % (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT 70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p = 0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk, intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5, and 57.8 %, respectively. Patients treated with IMRT achieved the following results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7 vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached 95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were statistically significant, while C-RFS and DFS were marginally better. Conclusion: Dose escalation with IMRT was associated with improved cancer control in intermediate- and high-risk patients in comparison with 3D-CRT, without compromising toxicity. © 2015, Springer-Verlag Berlin Heidelberg.
Wilson C.H.,The Freeman Hospital
The Cochrane database of systematic reviews | Year: 2013
Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from the vesicoureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting, at the time of graft implantation, to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications and some centres advocate a policy of only stenting selected anastomoses. To examine the benefits and harms of routine ureteric stenting to prevent urological complications in kidney transplant recipients. We searched the Cochrane Renal Group's Specialised Register (up to 8 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. All RCTs and quasi-RCTs were included in our meta-analysis. Four reviewers assessed the studies for quality against four criteria (allocation concealment, blinding, intention-to-treat and completeness of follow-up). The primary outcome was the incidence of MUCs. Further outcomes of interest were graft and patient survival and the incidence of adverse events (urinary tract infection (UTI), haematuria, irritative symptoms, pain and stent migration). Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). Seven RCTs (1154 patients) of low or moderate quality were identified. The incidence of MUCs was significantly reduced (RR 0.24, 95% CI 0.07 to 0.77, P = 0.02, NNT 13) by universal prophylactic stenting. This was dependent on whether the same surgeon performed, or was in attendance, during the operations. Two patients lost their grafts to infective urinary tract complications in the stented group. UTIs, in general, were more common in stented patients (RR 1.49, 95% CI 1.04 to 2.15) unless the patients were prescribed cotrimoxazole 480 mg/d: in which case the incidence was equivalent (RR 0.97, 95% CI 0.71 to 1.33). Stents appeared generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. Routine prophylactic stenting reduces the incidence of MUCs. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.
Robertson L.,The Freeman Hospital
The Cochrane database of systematic reviews | Year: 2013
Patients undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (for example heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT) but it is associated with an increased risk of bleeding. Mechanical prophylaxis (for example antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has no side effects. However, it is not always appropriate in patients with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis and whether this is one treatment alone or in combination with another. To date, no systematic review has been conducted examining the effectiveness of thromboprophylaxis in preventing VTE in people undergoing amputation. To determine the effectiveness of thromboprophylaxis in preventing VTE in people undergoing major amputation of the lower extremity. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2013) and CENTRAL (2013, Issue 4). Clinical trials databases were searched (May 2013). No date or language restrictions were applied. Non-English trials were translated where required and reference lists of identified studies were handsearched. Randomised controlled trials and quasi-randomised controlled trials in which people undergoing a major unilateral or bilateral amputation (for example hip disarticulation, transfemoral, knee disarticulation and transtibial) of the lower extremity were allocated to different types or regimens of thromboprophylaxis (including pharmacological or mechanical prophylaxis) or placebo. Selection of studies, data extraction and risk of bias were completed independently by two review authors. Any disagreements were resolved by discussion. Meta-analysis could not be completed as the two included studies compared different treatments and therefore the data could not be pooled. Two studies with a combined total of 288 participants met the inclusion criteria for this review. One study compared low molecular weight heparin with unfractionated heparin and found no difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35). No bleeding events or deaths occurred. This study was open label and therefore at a high risk of performance bias. Additionally, the method of randomisation was not reported and therefore the risk of selection bias was unclear. In the second study heparin did not significantly improve prevention of pulmonary embolism (OR 1.02, 95% CI 0.44 to 2.37) when compared to placebo. Furthermore, when the level of amputation was considered, the incidence of pulmonary embolism was similar between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97) and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent pulmonary embolism, all of whom had been on placebo. Bleeding events were reported in less than 10% of participants in both treatment groups but specific data were not presented. This study did not report the methods used to conceal allocation of treatment and therefore it was unclear if selection bias occurred. However, this study appeared to be free from all other sources of bias. No study looked at mechanical prophylaxis. As only two studies were included in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in patients undergoing lower limb amputation. Further large-scale studies that are of good quality are required.
Binai N.,Northumbria University |
O'Reilly S.,Northumbria University |
Griffiths B.,The Freeman Hospital |
van Laar J.M.,Northumbria University |
And 2 more authors.
PLoS ONE | Year: 2012
Background: Circulating monocytes are a highly plastic and functionally heterogeneic cell type with an activated phenotype in patients with systemic sclerosis (SSc). CD14 + monocytes have the potential to differentiate into extra-cellular matrix (ECM) producing cells, possibly participating in fibrogenesis. Aim: To study the effect of GM-CSF, IL-4 and endothelin -1 (ET-1) alone or in combination on monocyte differentiation into myofibroblasts. Methods: CD14 + cells were isolated from peripheral blood from 14 SSc patients and healthy controls by positive selection and incubated with different combinations of GM-CSF, IL-4 and ET-1 for 14 days. Type-1 collagen and α-SMA were detected by Western blot, qPCR and confocal microscopy. HLA-DR, CD11c and CD14 expression was analysed by flow cytometry. A collagen gel contraction assay was performed for functional myofibroblast assessment. Results: GM-CSF both induced collagen and α-SMA expression after 14 days. ET-1 further increased GM-CSF-induced collagen expression in a dose dependent manner up to 30-fold. IL-4/GM-CSF combination leads to a more DC-like phenotype of monocytes associated with reduced collagen and α-SMA expression compared to GM-CSF alone. Collagen and α-SMA expression was higher in monocytes from SSc patients and monocytes were more prone to obtain a spindle form. In contrast to controls, ET-1 and IL-4 alone were sufficient to induce α-SMA expression in monocytes from SSc patients. Despite the induction of α-SMA expression, monocyte-derived myofibroblasts only had a moderate capability of contraction in functional analyses. Conclusion: SSc monocytes display increased maturation towards myofibroblasts demonstrated by their phenotype and α-SMA expression when compared to monocytes from healthy controls, however only with minor functional contraction properties. © 2012 Binai et al.
Dudley N.,Lincoln County Hospital |
Russell S.,The Christie NHS Foundation Trust |
Ward B.,The Freeman Hospital |
Hoskins P.,University of Edinburgh
Ultrasound | Year: 2014
Quality Assurance of ultrasound systems is necessary to ensure the reliability of results and to check for deterioration in performance; a number of bodies have produced guidelines. Testing has traditionally been the responsibility of Medical Physics Departments but the important role of sonographers has been recognised and recent publications have included tests to be performed by ultrasound users. Since there are differences in approach between these publications the BMUS QA Working Party was established to provide a consistent set of guidelines specifically for sonographers. Three levels of testing are recommended, to include infection control and inspections for scanner and probe damage, basic display checks and further tests to assess drop-out, sensitivity and noise. These tests should form part of a programme that includes more comprehensive testing at longer intervals, perhaps by a Medical Physics Department.
Robertson L.,The Freeman Hospital
The Cochrane database of systematic reviews | Year: 2013
Chronic venous insufficiency (CVI) is a common problem, affecting up to 50% of the population in industrialised countries. It is a chronic condition which, if untreated, can progress to serious complications that in turn can interfere with working ability. Standing at work is a known risk factor for CVI, yet the true effect of non-pharmacological preventive strategies remains unknown. This is an update of a review first published in 2012. To assess the efficacy of non-pharmacological strategies and devices to prevent CVI in a standing worker population. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2013) and CENTRAL (2013, Issue 8). We also handsearched reference lists of relevant studies. Randomised and non-randomised controlled trials that recruited standing workers to evaluate non-pharmacological devices or strategies used to prevent CVI were eligible for inclusion. Trials had to report an objective measure of clinical features of CVI or complaints associated with this condition in order to be included. Selection of the trials, quality assessment and data abstraction were completed independently by two review authors. We resolved disagreements by discussion. Only one trial was eligible for inclusion in the review so we did not perform meta-analyses. The primary outcomes of this review were clinical features of CVI and its associated symptoms. No new included studies were identified for this update. One prospective cross-over trial was included in this review. It measured the effect of no compression followed by two phases with different gradients of compression stockings on symptoms in 19 female flight attendants who were required to stand, almost continuously, for long periods of time. The included study provided some evidence that compression stockings improved symptoms of leg fatigue in standing workers. However, the strength of the evidence in this review is weak as it is based on only one very small trial which was at high risk of bias. The included study did not address any of the secondary outcomes including quality of life or economic impact of the interventions. Nor did the study report the length of time that the population were required to stand at work. Furthermore, no trials were found which measured the effectiveness of other non-pharmacological interventions or strategies aimed at preventing CVI in standing workers. Due to the extremely limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of non-pharmacological interventions for preventing CVI in standing workers. Further large-scale studies examining all possible non-pharmacological interventions and outcomes are required.
Wilson C.H.,The Freeman Hospital
Cochrane database of systematic reviews (Online) | Year: 2011
Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The major disincentive to potential kidney donors is the pain and morbidity associated with open surgery. To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors. We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists. Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN). Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta-analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI -0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85). LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN-acquired grafts, although this has not been reported as being associated with short-term consequences.
O'Hara J.,The Freeman Hospital |
O'Hara J.,Newcastle University |
Goff D.,Speech Kingdom |
Cocks H.,Sunderland Royal Hospital |
And 5 more authors.
Clinical Otolaryngology | Year: 2016
Objectives: To assess the between-group change in swallowing function from baseline to 12 months following treatment, for patients treated for resectable stage III and IVA oropharyngeal squamous cell carcinoma. To assess the within-group change in swallowing function between 3 and 12 months following treatment. Design: Non-randomised cohort study. Setting: A single head and neck cancer unit with oncology services held at the nearby regional treatment centre. Participants: Twenty-five patients treated with Transoral Laser Microsurgery +/- adjuvant (chemo)radiotherapy (Transoral Laser Microsurgery) observed alongside an historic cohort of 33 patients treated with (chemo)radiotherapy. Main Outcome Measures: The patient reported MD Anderson Dysphagia Inventory (MDADI), an objective timed Water Swallow Test, and the clinician rated normalcy of diet subsection of the Performance of Swallowing Scale. Results: Between baseline and 12 months, patients treated with primary (chemo)radiotherapy demonstrated greater deterioration in swallowing function compared to Transoral Laser Microsurgery for all 3 swallowing measures. Between 3 and 12 months, the only significant change was an improvement in Performance of Swallowing Scale scores in the (chemo)radiotherapy group. Conclusions: This is the first study to report the results of a complimentary set of swallowing measures for patients treated with Transoral Laser Microsurgery, observed alongside a cohort of (chemo)radiotherapy patients. The preliminary results suggest a benefit in swallowing function for Transoral Laser Microsurgery over (chemo)radiotherapy during the year following treatment. © 2016 John Wiley & Sons Ltd.
McDonnell M.J.,Northumbria University |
Jary H.R.,Northumbria University |
Perry A.,The Freeman Hospital |
MacFarlane J.G.,Northumbria University |
And 6 more authors.
Respiratory Medicine | Year: 2014
Background: The hallmark of non-cystic fibrosis bronchiectasis is recurrent bronchial infection, yet there are significant gaps in our understanding of pathogen persistence, resistance and exacerbation frequencies. Pseudomonas aeruginosa is a key pathogen thought to be a marker of disease severity and progression, yet little is known if the infection risk is seen in those with milder disease or if there is any potential for eradication. These data are important in determining risk stratification and follow up. Methods and patient cohort: A retrospective review of consecutive adult patients attending a specialist UK bronchiectasis clinic over a two-year recruitment period between July 2007 and June 2009 was performed. Analysis of our primary outcome, longitudinal microbiological status, was recorded based on routine clinical follow-up through to data capture point or date of death. Patients were stratified by lung function and infecting organism. Results: 155 patients (mean (SD) age 62.2 (12.4) years; 60.1% female) were identified from clinic records with microbiological data for a median (IQR) follow up duration of 46 (35-62) months. Baseline mean FEV1% predicted was 60.6% (24.8) with mean exacerbation frequency of 4.42/year; 73.6% reported 3 or more exacerbations/year. Haemophilus influenzae was isolated in 90 (58.1%) patients and P. aeruginosa in 78 (50.3%) patients with persistent infection in 51 (56.7%) H. influenzae and 47 (60.3%) P. aeruginosa, respectively. Of the P. aeruginosa colonised patients, 16 (34%) became culture negative on follow-up with a mean of 5.2 negative sputum cultures/patient. P. aeruginosa was isolated from 5 out of 39 patients (12.8%) with minimal airflow limitation as compared to 18 out of 38 patients (47.4%) with severe airflow limitation. Although hospital admissions were significantly higher in the P. aeruginosa infected group (1.3 vs. 0.7 admissions per annum, p = 0.035), overall exacerbation rates were the same (4.6 vs. 4.3, p = 0.58). Independent predictors of P. aeruginosa colonisation were low FEV1% predicted (OR 2.46; 95% CI 1.27-4.77) and polymicrobial colonisation (OR 4.07; 95% CI 1.56-10.58). 17 (11%) patients were infected with multi-resistant strains; however, none were pan-resistant. Conclusions: P. aeruginosa is associated with greater persistent infection rates and more hospital admissions than H. influenzae. Exacerbation rates, however, were similar; therefore H. influenzae causes significant out-patient morbidity. P. aeruginosa infection occurs across all strata of lung function impairment but is infrequently multi-resistant in bronchiectasis. Careful microbiology follow up is required even in those with well-preserved lung function. © 2014 Elsevier Ltd. All rights reserved.
Richmond N.,James Cook University |
Allen V.,The Freeman Hospital |
Daniel J.,James Cook University |
Dacey R.,The Freeman Hospital |
Walker C.,James Cook University
Medical Dosimetry | Year: 2015
Flattening filter free (FFF) photon beams have different dosimetric properties from those of flattened beams. The aim of this work was to characterize the collimator scatter (Sc) and total scatter (Scp) from 3 FFF beams of differing quality indices and use the resulting mathematical fits to generate phantom scatter (Sp) data. The similarities and differences between Sp of flattened and FFF beams are described. Sc and Scp data were measured for 3 flattened and 3 FFF high-energy photon beams (Varian 6 and 10MV and Elekta 6MV). These data were fitted to logarithmic power law functions with 4 numerical coefficients. The agreement between our experimentally determined flattened beam Sp and published data was within ± 1.2% for all 3 beams investigated and all field sizes from 4 × 4 to 40 × 40cm2. For the FFF beams, Sp was only within 1% of the same flattened beam published data for field sizes between 6 × 6 and 14 × 14cm2. Outside this range, the differences were much greater, reaching - 3.2%, - 4.5%, and - 4.3% for the fields of 40 × 40cm2 for the Varian 6-MV, Varian 10-MV, and Elekta 6-MV FFF beams, respectively. The FFF beam Sp increased more slowly with increasing field size than that of the published and measured flattened beam of a similar reference field size quality index, i.e., there is less Phantom Scatter than that found with flattened beams for a given field size. This difference can be explained when the fluence profiles of the flattened and FFF beams are considered. The FFF beam has greatly reduced fluence off axis, especially as field size increases, compared with the flattened beam profile; hence, less scatter is generated in the phantom reaching the central axis. © 2015 American Association of Medical Dosimetrists.