Collins P.W.,University of Wales |
Palmer B.P.,UK National Haemophilia Database |
Chalmers E.A.,Royal Hospital for Sick Children |
Hart D.P.,Royal London Hospital |
And 5 more authors.
Blood | Year: 2014
The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These resultswill help informdebate around the relative immunogenicity and use of rFVIII brands. © 2014 by The American Society of Hematology.
Powles T.,Queen Mary, University of London |
Blank C.,Netherlands Cancer Institute |
Chowdhury S.,Guys And St Thomass Hospital |
Horenblas S.,Netherlands Cancer Institute |
And 11 more authors.
European Urology | Year: 2011
Background: The role of cytoreductive nephrectomy in metastatic clear cell renal cell carcinoma (ccRCC) is controversial. Objective: To determine the outcome of patients with metastatic ccRCC who receive sunitinib prior to planned nephrectomy. Design, setting, and participants: The study combined the data from two prospective phase 2 studies that assessed upfront sunitinib (12-16 wk) prior to nephrectomy in previously untreated patients with metastatic renal cell carcinoma (RCC). Sunitinib was discontinued during the perioperative period (median: 29 d). Intervention: Sunitinib 50 mg in six weekly cycles (4 wk on, 2 wk off). Measurements: Progression-free (PFS) and overall survival (OS) using the Kaplan-Meier method. Results and limitations: Twenty-one patients (32%) had Memorial Sloan-Kettering Cancer Centre (MSKCC) poor-risk disease; 45 (68%) had intermediate-risk disease. Nephrectomy was not performed in 19 (29%), most commonly due to disease progression (n = 12). The PFS for the cohort was 6.3 mo (95% confidence interval [CI], 5.1-8.5). Seventeen (36%) patients progressed during the treatment break, 13 (76%) of whom stabilised upon reinitiating of sunitinib. The OS for the cohort was 15.2 mo (95% CI, 10.3-NA). The OS for the intermediate MSKCC risk group was significantly longer than that for the poor-risk group (26.0 mo [95% CI, 13.6-NA] and 9.0 mo [95% CI, 5.8-20.5], respectively; p < 0.01). In multivariate analysis, progression of disease prior to planned nephrectomy (hazard ratio [HR]: 5.34; 95% CI, 3.17-13.27), high Fuhrman grade (HR 3.27; 95% CI, 1.38-7.72), and MSKCC poor risk at diagnosis (HR 4.75; 95% CI, 2.05-11.02) were associated with short survival (p < 0.01). However, in the absence of randomised studies it is not possible to determine if this approach is beneficial. Conclusions: Upfront sunitinib prior to planned nephrectomy in intermediate-risk disease is associated with a median survival of >2 yr despite frequent progression during treatment break. Progression in metastatic sites prior to planned surgery and MSKCC poor-risk disease was associated with a poor outcome. © 2011 European Association of Urology.
Hay C.R.M.,Royal Infirmary |
Palmer B.P.,The UK National Haemophilia Database |
Chalmers E.A.,Royal Hospital for Sick Children |
Liesner R.,Great Ormond Street Hospital |
And 4 more authors.
Haemophilia | Year: 2015
Summary: Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non-switchers. Centres were requested to test all the patients for inhibitors prior to the switching date and 6-monthly thereafter. Positive and negative inhibitor test data were also collected to analyse for testing bias. A total of 1198 patients with severe haemophilia A and treated with Advate, Kogenate/Helixate or Refacto AF preswitch were included in the analysis, of whom 516 switched to Refacto-AF and 682 did not switch products. Five new inhibitors were reported amongst previously treated patients (>50 exposure days) with a median titre at the time of detection of 1.25 BU mL-1 (IQR 0.7-23.05). One inhibitor occurred in a non-switcher using Kogenate, an incidence of 1.5 per 1000 treatment-years (95% CI 0.2-10.5). Four inhibitors arose in patients who had switched from Kogenate (two) or Advate (two) to ReFacto-AF, an incidence of 7.8 per 1000 treatment-years (95% CI 2.9-20.8). These incidence rates did not differ significantly from one another (incidence rate ratio 5.3 (95% CI 0.5-260.3) or from the historical rate of 6.05 inhibitors/1000 treatment-years (95% CI 5.18-7.06). Only one inhibitor (non-switcher) persisted. Non-switchers were significantly older (P = 0.03), and used significantly less FVIII per year (P = 0.005) prior to switching. Following switching, factor usage increased similarly (P = 0.53) in both groups. Switching from FLRFVIII to Refacto-AF (BDDRFVIII) was not associated with an increased inhibitor development. © 2014 John Wiley & Sons Ltd.
Child N.,Guys And St Thomass Hospital |
Child N.,King's College London |
Hanson B.,University College London |
Bishop M.,King's College London |
And 10 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2014
Background-Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Methods and Results-Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged flm clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the flm clip (P=0.001). APD decreased during the stressful parts of the flm clip, for example, for global right ventricular activation recovery interval at end of flm clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end flm left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the flm clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Conclusions-Our results document for the frst time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.
Raza S.J.,Roswell Park Cancer Institute |
Wilson T.,Beckman Research Institute |
Peabody J.O.,Ford Motor Company |
Wiklund P.,Karolinska University Hospital |
And 17 more authors.
European Urology | Year: 2015
Background Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) are limited and based largely on single-institution series. Objective Report survival outcomes of patients who underwent RARC ≥5 yr ago. Design, setting, and participants Retrospective review of the prospectively populated International Robotic Cystectomy Consortium multi-institutional database identified 743 patients with RARC performed ≥5 yr ago. Clinical, pathologic, and survival data at the latest follow-up were collected. Patients with palliative RARC were excluded. Final analysis was performed on 702 patients from 11 institutions in 6 countries. Intervention RARC. Outcome measurements and statistical analysis Outcomes of interest, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were plotted using Kaplan-Meier survival curves. A Cox proportional hazards model was used to identify factors that predicted outcomes. Results and limitations Pathologic organ-confined (OC) disease was found in 62% of patients. Soft tissue surgical margins (SMs) were positive in 8%. Median lymph node (LN) yield was 16, and 21% of patients had positive LNs. Median follow-up was 67 mo (interquartile range: 18-84 mo). Five-year RFS, CSS, and OS were 67%, 75%, and 50%, respectively. Non-OC disease and SMs were associated with poorer RFS, CSS, and OS on multivariable analysis. Age predicted poorer CSS and OS. Adjuvant chemotherapy and positive SMs were predictors of RFS (hazard ratio: 3.20 and 2.16; p < 0.001 and p < 0.005, respectively). Stratified survival curves demonstrated poorer outcomes for positive SM, LN, and non-OC disease. Retrospective interrogation and lack of contemporaneous comparison groups that underwent open radical cystectomy were major limitations. Conclusions The largest multi-institutional series to date reported long-term survival outcomes after RARC. Patient summary Patients who underwent robot-assisted radical cystectomy for bladder cancer have acceptable long-term survival. © 2015 European Association of Urology.
Thwaites G.E.,Imperial College London |
Duong T.,London School of Hygiene and Tropical Medicine |
de Silva C.,University of Liverpool |
Edgeworth J.,Guys And St Thomass Hospital |
And 3 more authors.
PLoS ONE | Year: 2010
Background: Staphylococcus aureus bacteremia is a common and serious infection worldwide and although treatment guidelines exist, there is little consensus on optimal management. In this study we assessed the variation in management and adherence to treatment guidelines of S. aureus bacteremia. Methodology/Principal Findings: We prospectively recorded baseline clinical characteristics, management, and in-hospital outcome of all adults with S. aureus bacteremia treated consecutively over one year in eight centres in the United Kingdom, three in Vietnam and one in Nepal. 630 adults were treated for S. aureus bacteremia: 549 in the UK (21% methicillinresistant), 80 in Vietnam (19% methicillin-resistant) and 1 in Nepal. In the UK, 41% had a removable infection focus (50% intravenous catheter-related), compared to 12% in Vietnam. Significantly (p<0.001) higher proportions of UK than Vietnamese patients had an echocardiogram (50% versus 28%), received more than 14 days antibiotic therapy (84% versus 44%), and received >50% of treatment with oral antibiotics alone (25% versus 4%). UK centres varied significantly (p<0.01) in the proportions given oral treatment alone for >50% of treatment (range 12-40%), in those treated for longer than 28 days (range 13-54%), and in those given combination therapy (range 14-94%). 24% died during admission: older age, time in hospital before bacteremia, and an unidentified infection focus were independent predictors of in-hospital death (p<0.001). Conclusions/Significance: The management of S. aureus bacteremia varies widely between the UK and Vietnam and between centres in the UK with little adherence to published guidelines. Controlled trials defining optimal therapy are urgently required. © 2010 Thwaites, United Kingdom Clinical Infection Research Group (UKCIRG).
Howard L.S.,Hammersmith Hospital |
Grapsa J.,Imperial College Healthcare NHS Trust |
Dawson D.,Imperial College Healthcare NHS Trust |
Bellamy M.,Imperial College Healthcare NHS Trust |
And 4 more authors.
European Respiratory Review | Year: 2012
Patients with suspected pulmonary hypertension (PH) should be evaluated using a multimodality approach to ensure that they receive a correct diagnosis. The series of investigations required includes clinical evaluation, noninvasive imaging techniques and right heart catheterisation (considered to be the "gold standard" for the diagnosis of PH). Current guidelines recommend that a detailed echocardiographic assessment is performed in all patients with suspected PH. In this review we summarise a protocol adopted by the National Pulmonary Hypertension Centres of UK and Ireland and approved by the British Society of Echocardiography for the evaluation of these patients. The views and measurements described are recommended for diagnosis, assisting in prognosis and providing a noninvasive means of following disease progression or response to therapy. © ERS 2012.
Zaidi A.,University of London |
Sheikh N.,University of London |
Jongman J.K.,Isala Clinics |
Gati S.,University of London |
And 6 more authors.
Journal of the American College of Cardiology | Year: 2015
Background Physiological cardiac adaptation to regular exercise, including biventricular dilation and T-wave inversion (TWI), may create diagnostic overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC). Objectives The goal of this study was to assess the accuracy of diagnostic criteria for ARVC when applied to athletes exhibiting electrocardiographic TWI and to identify discriminators between physiology and disease. Methods The study population consisted of athletes with TWI (n = 45), athletes without TWI (n = 35), and ARVC patients (n = 35). Subjects underwent electrocardiography (ECG), signal-averaged electrocardiography (SAECG), echocardiography, cardiac magnetic resonance imaging (CMRI), Holter monitoring, and exercise testing. Results There were no electrical, structural, or functional cardiac differences between athletes exhibiting TWI and athletes without TWI. When athletes were compared with ARVC patients, markers of physiological remodeling included early repolarization, biphasic TWI, voltage criteria for right ventricular (RV) or left ventricular hypertrophy, and symmetrical cardiac enlargement. Indicators of RV pathology included the following: syncope; Q waves or precordial QRS amplitudes <1.8 mV; 3 abnormal SAECG parameters; delayed gadolinium enhancement, RV ejection fraction ≤45%, or wall motion abnormalities at CMRI; >1,000 ventricular extrasystoles (or >500 non-RV outflow tract) per 24 h; and symptoms, ventricular tachyarrhythmias, or attenuated blood pressure response during exercise. Nonspecific parameters included the following: prolonged QRS terminal activation; 2 abnormal SAECG parameters; RV dilation without wall motion abnormalities; RV outflow tract ectopy; and exercise-induced T-wave pseudonormalization. Conclusions TWI and balanced biventricular dilation are likely to represent benign manifestations of training in asymptomatic athletes without relevant family history. Diagnostic criteria for ARVC are nonspecific in such individuals. Comprehensive testing using widely available techniques can effectively differentiate borderline cases. © 2015 American College of Cardiology Foundation.
Kichenaradjou A.,Guys And St Thomass Hospital |
Beale V.R.,Guys And St Thomass Hospital |
Haers P.E.,Guys And St Thomass Hospital
International Journal of Oral and Maxillofacial Surgery | Year: 2010
The authors report a cystic lesion within a previous unilateral cleft lip and alveolus bone graft site in a 15-year-old girl, 5 years after the secondary bone graft. The cyst comprised respiratory epithelial lining, which is thought to be a remnant of the nasal mucosal lining of the primary cleft. © 2010 International Association of Oral and Maxillofacial Surgeons.
Pezier T.,Guys And St Thomass Hospital |
Nixon I.J.,Guys And St Thomass Hospital |
Gurney B.,Guys And St Thomass Hospital |
Schilling C.,Guys And St Thomass Hospital |
And 6 more authors.
Annals of Surgical Oncology | Year: 2012
Background. Sentinel lymph node biopsy (SLNB) is an established technique in breast and melanoma surgery and is gaining acceptance in the management of oral cavity squamous cell carcinoma. We report a single institution's experience of SLNB between 2006 and 2010. Methods. Prospective consecutive cohort study of 59 patients recruited between 2006 and 2010. All patients underwent SLNB with preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel nodes were evaluated with step-serial sectioning and immunohistochemistry. Endpoints included: overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and regional recurrencefree survival (RRFS). Results. A total of 59 patients (36 male and 23 female) were operated on. Of these, 42 patients (71%) were pT1 and 17 patients (29%) were pT2. In two patients the sentinel node was not identified and proceeded to elective neck dissection. A total of 150 nodes were harvested from the remaining 57 patients of which 21 nodes were positive in 17 patients; three patients had positive contralateral nodes. The 2-year OS, DSS, LRFS, and RRFS for the SLNB negative patients were 97.5, 100, 95.8, and 95.8% and for the SLNB positive patients 68.2, 81.8, 83.9, and 100% respectively. Only OS and DSS approached statistical significance with P values of 0.07 and 0.06. Conclusions. SLNB is a safe and accurate diagnostic technique for staging the neck with a negative predictive value in our series of 97.5%. Furthermore, in our series three patients (5%) had positive contralateral neck drainage that would have been missed by conventional ipsilateral neck dissection. © Society of Surgical Oncology 2012.