Sport Satellite Account for the UK 2010

The value of sport to the UK economy has grown since 2008 in terms of output. In current (non-adjusted) prices, sport GVA is worth £33.8bn, or 2.7% of economy wide GVA. Sport-related consumer spending is now worth £26.6bn or 3.0% of UK spending but this proportion has remained static since 2008. And employment is 639,000 in the sport economy which, notwithstanding the 1% increase between 2008 and 2010, has fallen as a proportion of total employment to 2.2% from 2.5% in 2008

Derived neutrophil to lymphocyte ratio as a prognostic factor in patients with advanced colorectal cancer according to RAS and BRAF status: a post-hoc analysis of the MRC COIN study.

The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out. All patients with available white blood cell and neutrophil data were analysed. The dNLR was calculated using a formula that has previously shown predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined as a value of 2.2 or more. dNLR was correlated with clinical outcomes using Kaplan-Meier and Cox regression analysis. A total of 1603 patients were assigned to the oxaliplatin-based chemotherapy (arm A, N=815) or oxaliplatin-based chemotherapy plus cetuximab (arm B, N=815) arms. There was a strong association between dNLR level and overall survival (OS) using Kaplan-Meier analysis. In all mutation groups, dNLR less than 2.2 was associated with better OS compared to dNLR of 2.2 or more. The median OS in patients with wild-type disease (dNLR<2.2 vs. dNLR≥2.2) was 22.8 versus 13.1 months [hazard ratio (HR)=1.33]; 16.9 versus 11.8 months (HR=1.36) in patients with RAS mutant tumours; and 12.6 versus 6.8 months (HR=1.67) in patients with BRAF mutant tumours. In patients with dNLR less than 2.2, the median OS was 19.2 months in arm A compared to 18.0 months in arm B (HR=1.11). Among patients with dNLR greater than or equal to 2.2, the median OS was 13.0 months in arm A compared with 13.1 months in arm B (HR=0.96). dNLR is strongly prognostic for survival in all mutation groups. dNLR does not predict for benefit from the addition of cetuximab

Endoscopists attitudes on the publication of "quality" data for endoscopic procedures: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Whilst the public now have access to mortality & morbidity data for cardiothoracic surgeons, such "quality" data for endoscopy are not generally available. We studied endoscopists' attitudes to and the practicality of this data being published.</p> <p>Methods</p> <p>We sent a questionnaire to all consultant gastrointestinal (GI) surgeons, physicians and medical GI specialist registrars in the Northern region who currently perform GI endoscopic procedures (n = 132). We recorded endoscopist demographics, experience and current data collection practice. We also assessed the acceptability and utility of nine items describing endoscopic "quality" (e.g. mortality, complication & completion rates).</p> <p>Results</p> <p>103 (78%) doctors responded of whom 79 were consultants (77%). 61 (59%) respondents were physicians. 77 (75%) collect any "quality" data. The most frequently collected item was colonoscopic completion rate. Data were most commonly collected for appraisal, audit or clinical governance. The majority of doctors (54%) kept these data only available to themselves, and just one allowed the public to access this. The most acceptable data item was annual number of endoscopies and the least was crude upper GI bleeding mortality. Surgeons rated information less acceptable and less useful than physicians. Acceptability and utility scores were not related to gender, length of experience or current activity levels. Only two respondents thought all items totally unacceptable and useless.</p> <p>Conclusion</p> <p>The majority of endoscopists currently collect "quality" data for their practice although these are not widely available. The endoscopists in this study consider the publication of their outcome data to be "fairly unacceptable/not very useful" to "neutral" (score 2–3). If these data were made available to patients, consideration must be given to both its value and its acceptability.</p

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study

BACKGROUND: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer. METHODS: A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR=ANC/(WBC−ANC). A high dNLR was defined using a cut-off value of ⩾2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan–Meier method. Comparison between groups was performed using Cox regression. RESULTS: A total of 1630 patients were assigned to the continuous (N=815) or intermittent (N=815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR=1.70; 95% CI=1.52–1.90; P<0.001). The estimate of the hazard ratio did not alter substantially (HR=1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count. CONCLUSIONS: Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy

Degenerative mitral valve regurgitation: best practice revolution

Degenerative mitral valve disease often leads to leaflet prolapse due to chordal elongation or rupture, and resulting in mitral valve regurgitation. Guideline referral for surgical intervention centres primarily on symptoms and ventricular dysfunction. The recommended treatment for degenerative mitral valve disease is mitral valve reconstruction, as opposed to valve replacement with a bioprosthetic or mechanical valve, because valve repair is associated with improved event free survival. Recent studies have documented a significant number of patients are not referred in a timely fashion according to established guidelines, and when they are subjected to surgery, an alarming number of patients continue to undergo mitral valve replacement. The debate around appropriate timing of intervention for asymptomatic severe mitral valve regurgitation has put additional emphasis on targeted surgeon referral and the need to ensure a very high rate of mitral valve repair, particularly in the non-elderly population. Current clinical practice remains suboptimal for many patients, and this review explores the need for a ‘best practice revolution’ in the field of degenerative mitral valve regurgitation

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

BACKGROUND: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes. METHODS: Changes in 15 circulating plasma angiogenesis or inflammatory-related proteins and cytokeratin-18 (CK18), measured at baseline and during therapy until disease progression, were correlated with overall survival (OS) using time-varying covariate Cox models (TVC). RESULTS: Samples were available from n=117/124 (94%) patients. Circulating Ang1&2, FGFb, PDGFbb, VEGFC, VEGFR1 and CK18 decreased as a result of the therapy, independent of treatment with cediranib. Circulating VEGFR2 and Tie2 were preferentially reduced by cediranib. Patients with increasing levels of VEGFA at any time had a worse PFS and OS; this detrimental effect was attenuated in patients receiving cediranib. TVC analysis revealed CK18 and VEGFR2 increases correlated with poorer OS in all patients (P< 0.001 and P=0.02, respectively). CONCLUSIONS: Rising circulating VEGFA levels in patients with ABC, treated with CisGem, are associated with worse PFS and OS, not seen in patients receiving cediranib. Rising levels of markers of tumour burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation

3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT.

BACKGROUND: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. OBJECTIVES: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. DESIGN: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. SETTING: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. PARTICIPANTS: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. INTERVENTIONS: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. RESULTS: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. CONCLUSIONS: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894)