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There has been a substantially increased interest in biomedical research impact assessment over the past 5 years. This can be studied by a number of methods, but its influence on clinical guidelines must rank as one of the most important. In cancer, there are 43 UK guidelines (and associated Health Technology Assessments) published (up to October 2006) across three series, each of which has an evidence base in the form of references, many of which are papers in peer-reviewed journals. These have all been identified and analysed to determine their geographical provenance and type of research, in comparison with overall oncology research published in the peak years of guideline references (1999-2001). The UK papers were cited nearly three times as frequently as would have been expected from their presence in world oncology research (6.5%). Within the United Kingdom, Edinburgh and Glasgow stood out for their unexpectedly high contributions to the guidelines' scientific base. The cited papers from the United Kingdom acknowledged much more explicit funding from all sectors than did the UK cancer research papers at the same research level. [ABSTRACT FROM AUTHOR]

This paper reports on two studies that used qualitative thematic and quantitative linguistic analysis, respectively, to assess the content and language of the largest ever sample of graded research impact case studies, from the UK Research Excellence Framework 2014 (REF). The paper provides the first empirical evidence across disciplinary main panels of statistically significant linguistic differences between high- versus low-scoring case studies, suggesting that implicit rules linked to written style may have contributed to scores alongside the published criteria on the significance, reach and attribution of impact. High-scoring case studies were more likely to provide specific and high-magnitude articulations of significance and reach than low-scoring cases. High-scoring case studies contained attributional phrases which were more likely to attribute research and/or pathways to impact, and they were written more coherently (containing more explicit causal connections between ideas and more logical connectives) than low-scoring cases. High-scoring case studies appear to have conformed to a distinctive new genre of writing, which was clear and direct, and often simplified in its representation of causality between research and impact, and less likely to contain expressions of uncertainty than typically associated with academic writing. High-scoring case studies in two Main Panels were significantly easier to read than low-scoring cases on the Flesch Reading Ease measure, although both high-scoring and low-scoring cases tended to be of "graduate" reading difficulty. The findings of our work enable impact case study authors to better understand the genre and make content and language choices that communicate their impact as effectively as possible. While directly relevant to the assessment of impact in the UK's Research Excellence Framework, the work also provides insights of relevance to institutions internationally who are designing evaluation frameworks for research impact. [ABSTRACT FROM AUTHOR]

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point 'relative effectiveness scale', which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts. [ABSTRACT FROM AUTHOR]

Scholars on both sides of the Atlantic have grappled with the difficulties of conducting comparative research on rural issues in general, and on rural poverty and inequality in particular. Shortall and Warner have observed that "The UK-US dialog is highly illustrative of how seemingly similar situations turn out to be full of complexity and difference." That complexity and difference can serve to turn researchers away from comparative collaborations. We begin our paper with an overview of some of the general differences (and similarities) between how rural scholars in the UK and US have examined poverty and inequality in rural areas. Analysis of the two welfare regimes in these countries provides the backdrop for examining specific aspects of deprivation for rural people and communities. Our paper draws on our experience as members of a trans-Atlantic research group to illustrate the type of organisational infrastructure that can support international, interdisciplinary collaboration. We conclude by offering suggestions for future comparative research. Our paper progresses earlier debates in rural studies on the challenges of doing comparative US-UK analysis. [ABSTRACT FROM AUTHOR]

Wearable inertial measurement units (IMUs) are being used to quantify gait characteristics that are associated with increased fall risk, but the current limitation is the lack of contextual information that would clarify IMU data. Use of wearable video-based cameras would provide a comprehensive understanding of an individual's habitual fall risk, adding context to clarify abnormal IMU data. Generally, there is taboo when suggesting the use of wearable cameras to capture real-world video, clinical and patient apprehension due to ethical and privacy concerns. This perspective proposes that routine use of wearable cameras could be realized within digital medicine through AI-based computer vision models to obfuscate/blur/shade sensitive information while preserving helpful contextual information for a comprehensive patient assessment. Specifically, no person sees the raw video data to understand context, rather AI interprets the raw video data first to blur sensitive objects and uphold privacy. That may be more routinely achieved than one imagines as contemporary resources exist. Here, to showcase/display the potential an exemplar model is suggested via off-the-shelf methods to detect and blur sensitive objects (e.g., people) with an accuracy of 88%. Here, the benefit of the proposed approach includes a more comprehensive understanding of an individual's free-living fall risk (from free-living IMU-based gait) without compromising privacy. More generally, the video and AI approach could be used beyond fall risk to better inform habitual experiences and challenges across a range of clinical cohorts. Medicine is becoming more receptive to wearables as a helpful toolbox, camera-based devices should be plausible instruments. [ABSTRACT FROM AUTHOR]

Background: Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence. Aim: To assess the cost-effectiveness of drugs used to treat adults with chronic migraine. Methods: We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes. Results: Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY. Conclusions: Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications. [ABSTRACT FROM AUTHOR]

This paper investigates the effect of proprietary costs in relation to managers' decisions to disclose information. Further, we look into the impact of factors affecting the timing of disclosures in a comparative study of Spain and the UK. Our investigation focuses on management earnings press releases discussing annual results. These press releases allow managers great discretion in terms of the decision to release and the timing. Our results show that the potential for growth is negatively related to the likelihood of a company voluntarily issuing a press release. Moreover, once the decision to voluntarily disclose is made, the timing is also relevant. We find significant differences in the timing of press releases between the two countries examined in this study. Also, significant differences between companies having or not having an investor relations department are evident. The existence of an investor relations function in the company seems to have a different impact depending on the country. Interestingly, even though corporate performance seems not to have a direct effect on the timing of the press release, this factor is moderated by the country where companies operate. [ABSTRACT FROM AUTHOR]

Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research priorities. The study adopted a participatory approach using a collaborative model that sought joint ownership of the study with people affected by cancer. An exploratory, qualitative approach was used. Consultation groups were the main method, combining focus group and nominal group techniques. Seventeen groups were held with a total of 105 patients broadly representative of the UK cancer population. Fifteen areas for research were identified. Top priority areas included the impact cancer has on life, how to live with cancer and related support issues; risk factors and causes of cancer; early detection and prevention. Although biological and treatment related aspects of science were identified as important, patients rated the management of practical, social and emotional issues as a higher priority. There is a mismatch between the research priorities identified by participants and the current UK research portfolio. Current research activity should be broadened to reflect the priorities of people affected by the disease. [ABSTRACT FROM AUTHOR]

This paper presents the first full micro costing of a commonly used cancer genetic counselling and testing protocol used in the UK. Costs were estimated for the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a questionnaire to all staff, conducting an audit of clinic rooms and equipment and obtaining gross unit costs from the finance department. A total of 22 distinct event pathways were identified for patients at risk of developing breast, ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were pound sterling 97- pound sterling 151 for patients at moderate risk, pound sterling 975- pound sterling 3072 for patients at high risk of developing colorectal cancer and pound sterling 675- pound sterling 2909 for patients at high risk of developing breast or ovarian cancer. The most expensive element of cancer genetic services was labour. Labour costs were dependent upon the amount of labour, staff grade, number of counsellors used and the proportion of staff time devoted to indirect patient contact. With the growing demand for cancer genetic services and the growing number of national and regional cancer genetic centers, there is a need for the different protocols being used to be thoroughly evaluated in terms of costs and outcomes. [ABSTRACT FROM AUTHOR]

This paper examines the work ethic characteristics of particular practising Protestant, Catholic and Muslim managers in Britain, Ireland and Turkey. Max Weber, argued that Protestant societies had a particular work ethic which was quite distinct from non-Protestant societies. The Protestant work ethic (PWE) thesis of Weber was reviewed. Previous empirical and analytical research results showed that the number of research results which support Weberian ideas were more than those which did not support. Methodological issues were also discussed. Results revealed that there was a considerable difference between Muslim and other groups in terms of PWE characteristics. The Muslim group showed the highest PWE level, while the Protestant group was placed second and the Catholic group third. The Protestant group showed a slightly higher of PWE level than the Catholic group. The possible reasons for the higher level of the PWE values of Muslim managers are discussed in the light of historical, political, social and economic developments in Turkey. [ABSTRACT FROM AUTHOR]

In this paper, queuing theory is tested through an examination of the occupational attainment of six groups of non-whites in London and New York. Workers in the dominant economy are distinguished from those in the niche economy and emphasis is placed on the former. Black male immigrants in New York and black female immigrants in London hold more favorable occupational status. These results reflect differences in (1) the presence of indigenous minorities--African Americans and Puerto Ricans--in New York but not London, and (2) the relatively low position of indigenous minority males compared to the relatively middling position of indigenous minority females in New York's labor queue. [ABSTRACT FROM AUTHOR]

Remote digital postoperative wound monitoring provides an opportunity to strengthen postoperative community care and minimise the burden of surgical-site infection (SSI). This study aimed to pilot a remote digital postoperative wound monitoring service and evaluate the readiness for implementation in routine clinical practice. This was a single-arm pilot implementational study of remote digital postoperative wound monitoring across two tertiary care hospitals in the UK (IDEAL stage 2b, clinicaltrials.gov: NCT05069103). Adults undergoing abdominal surgery were recruited and received a smartphone-delivered wound assessment tool for 30-days postoperatively. Patients received 30-day postoperative follow-up, including the Telehealth Usability Questionnaire (TUQ). A thematic mixed-methods approach was used, according to the WHO framework for monitoring and evaluating digital health interventions. 200 patients were enroled, of whom 115 (57.5%) underwent emergency surgical procedures. Overall, the 30-day SSI rate was 16.5% (n = 33/200), with 72.7% (n = 24) diagnosed post-discharge. Usage of the intervention was 83.0% (n = 166/200), with subsequently 74.1% (n = 123/166) TUQ completion. There were no issues reported with feasibility of the technology, with the reliability (3.87, 95% CI: 3.73–4.00) and quality of the interface rated highly (4.18, 95%: 4.06–4.30). Patient acceptance was similarly high with regards to ease of use (4.51, 95% CI: 4.41–4.62), satisfaction (4.27, 95% CI: 4.13–4.41), and usefulness (4.07, 95% CI: 3.92–4.23). Despite the desire for more frequent and personalised interactions, the majority viewed the intervention as providing meaningful benefit over routine postoperative care. Remote digital postoperative wound monitoring successfully demonstrated readiness for implementation with regards to the technology, usability, and healthcare process improvement. [ABSTRACT FROM AUTHOR]

Background: Long-term cancer survivors in the United Kingdom are mostly followed up in a primary care setting by their general practitioner; however, there is little research on the use of services. This study examines whether cancer survivors receive adequate screening and preventative care in UK primary care.Patients and Methods: We identified a cohort of long-term survivors of breast, colorectal and prostate cancer with at least a 5-year survival using the General Practice Research Database, with controls matched for age, gender and practice. We compared adherence with cancer screening and the use of preventative care between cancer survivors and controls.Results: The cancer survivors' cohort consisted of 18 612 breast, 5764 colorectal and 4868 prostate cancer survivors. Most cancer survivors receive cancer screening at the same levels as controls, except for breast cancer survivors who were less likely to receive a mammogram than controls (OR=0.78, 95% CI: 0.66-0.92). Long-term cancer survivors received comparable levels of influenza vaccinations and cholesterol tests, but breast (OR 0.81, 95% CI: 0.74-0.87) and prostate cancer survivors (OR=0.70, 95% CI: 0.57-0.87) were less likely to receive a blood pressure test. All survivors were more likely to receive bone densitometry.Conclusion: The provision and uptake of preventive care in a primary care setting in the United Kingdom is comparable between the survivors of three common cancers and those who have not had cancer. However, long-term breast cancer survivors in this cohort were less likely to receive a mammogram. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the ability of older adults, younger adults and nutritionists to assess portion size using traditional methods versus a computer-based method. This was to inform the development of a novel dietary assessment method for older adults “The NANA system”.Design: Older and younger adults assessed the portion size of self-served portions of foods from a buffet style set up using traditional and computerised portion size assessment aids. Nutritionists assessed the portion size of foods from digital photographs using computerised portion size aids. These estimates were compared to known weights of foods using univariate analyses of covariance (ANCOVA).Setting: The University of Sheffield, United Kingdom.Subjects: Forty older adults (aged 65 years and over), 41 younger adults (aged between 18 and 40 years) and 25 nutritionists.Results: There was little difference in the abilities of older and younger adults to assess portion size using both assessment aids with the exception of small pieces morphology. Even though the methods were not directly comparable among the test groups, there was less variability in portion size estimates made by the nutritionists.Conclusion: Older adults and younger adults are similar in their ability to assess food portion size and demonstrate wide variability of estimation compared to the ability of nutritionists to estimate portion size from photographs. The results suggest that the use of photographs of meals consumed for portion size assessment by a nutritionist may improve the accuracy of dietary assessment. Improved portion size assessment aids are required for all age groups. [ABSTRACT FROM AUTHOR]

Purpose: To report the outcomes of combined phacoemulsification and -deep sclerectomy (phaco-DS) from a single UK centre over a 10-year period.Methods: Retrospective analysis of phaco-DS data extracted from an ongoing glaucoma surgery database within Calderdale and Huddersfield NHS Trust. Two hundred and ninety-six eyes of 282 patients were included. Data included patient demographics, pre- and postoperative intraocular pressure (IOP), use of mitomycin C (MMC), spacer device implantation, and follow-up details including surgical success rates. IOP success criteria were: (A) IOP <19 mm Hg and/or 20% decrease from baseline and (B) IOP <16 mm Hg and/or 30% drop from baseline.Results: Mean follow-up was 63.5 ± 35.3 months. MMC was applied in 145 eyes (49%). Kaplan-Meier success rates in all eyes for criteria A were 89.1% and 80% with glaucoma medications (qualified success) and 81.2% and 68.3% without medications (unqualified success) at 2 and 5 years, respectively. Qualified success for criteria B was 72.4 and 61.4% and unqualified rates were 67.2 and 55.2% for the same time periods. Repeated-measures ANOVA showed significantly lower IOP in the phaco-DS with MMC group up to 3 years postoperatively (P = 0.002). Cox's proportional hazards for criteria B, however, showed no significant effect of MMC application in the long term (P = 0.2). Increasing age and laser goniopuncture were positively associated with success, whereas the absence of spacer devices was negatively associated. At last follow-up, 20% of eyes were on glaucoma medications. Complication rates were low with hypotony rates of 0.68%.Conclusions: This study confirms the long-term safety and efficacy of phaco-DS as a primary glaucoma procedure. [ABSTRACT FROM AUTHOR]

Background:Outcomes for older people with cancer are poorer in the United Kingdom compared with that in other countries. Despite this, the UK oncology curricula do not have dedicated geriatric oncology learning objectives. This cross-sectional study of UK medical oncology trainees investigates the training, confidence level and attitudes towards treating older people with cancer.Methods:A web-based survey link was sent to the delegates of a national medical oncology trainee meeting. Responses were collected in October 2011.Results:The response rate was 93% (64 out of 69). The mean age of the respondents was 32.3 years (range 27-42 years) and 64.1% were female. A total of 66.1% of the respondents reported never receiving training on the particular needs of older people with cancer, 19.4% reported to have received this training only once. Only 27.1% of the trainees were confident in assessing risk to make treatment recommendations for older patients compared with 81.4% being confident to treat younger patients. Even fewer were confident with older patients with dementia (10.2%).Conclusion:This first study of the UK medical oncology trainees highlights the urgent need for change in curricula to address the complex needs of older people with cancer. [ABSTRACT FROM AUTHOR]

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We compare meteorological data collected at the Met Office Research Unit, Cardington, UK with similar data from a temporary meteorological station located approximately 8.5 km away. Data were examined for a period of 10 months to ascertain differences in mean quantities, and in heat and radiation budgets, at different heights between the two locations, one of which is located in a wide shallow valley, the other on a plateau at the valley edge. Results reveal that screen-level variables at the two sites show the greatest differences in mean quantities, for most conditions, but that at 50 m the differences are negligible, indicating that temperatures had become aggregated and homogeneous at that height. For flux measurements between 10 and 50 m, however, significant differences were observed at certain times of the year, which appear to be related to local vegetation and soil conditions, and these are discussed. The study also presents data for stable conditions that show that temperature differences at screen level are again the most significant difference between the two sites. On average these were not large, but on occasions discrepancies at low levels (up to approximately 10 m) as large as 5°C were observed. It is thought that these greater differences during stable conditions may be caused by cold air pooling at the valley site, despite the very shallow orography there. Data from the two sites have been compared with forecasts from two Met Office mesoscale models. Results show that, during daytime hours, model-predicted values lie outside the range of values observed at the two sites, indicating a possible model bias. However, the opposite was true for most nighttime hours, during which model values fell within the range observed at the two sites, indicating that at night the model predictions are representative of the region. In this case, however, comparison of the model prediction with either one of the available observations could lead to the false conclusion that the model temperatures were either too high or too low, depending on which observational site was used for the comparison. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses the diagnosed population-attributable fraction (PAF) cancers in women in Great Britain in 2010 due to their past or current use of hormonal preparations. The study used general practice research database (GPRD) to examine the impact of the preparations and carcinogenicity testing with oestrogen-progestogen menopausal therapy in the breast. Results show that the prevalence of female sex hormones use is found to be greatest in women ages 20-24.

This chapter summarises the results of the preceding sections, which estimate the fraction of cancers occurring in the UK in 2010 that can be attributed to sub-optimal, past exposures of 14 lifestyle and environmental risk factors. For each of 18 cancer types, we present the percentage of cases attributable to one or all of the risk factors considered (tobacco, alcohol, four elements of diet (consumption of meat, fruit and vegetables, fibre, and salt), overweight, lack of physical exercise, occupation, infections, radiation (ionising and solar), use of hormones, and reproductive history (breast feeding)).Exposure to less than optimum levels of the 14 factors was responsible for 42.7% of cancers in the UK in 2010 (45.3% in men, 40.1% in women)--a total of about 134,000 cases.Tobacco smoking is by far the most important risk factor for cancer in the UK, responsible for 60, 000 cases (19.4% of all new cancer cases) in 2010. The relative importance of other exposures differs by sex. In men, deficient intake of fruits and vegetables (6.1%), occupational exposures (4.9%) and alcohol consumption (4.6%) are next in importance, while in women, it is overweight and obesity (because of the effect on breast cancer)--responsible for 6.9% of cancers, followed by infectious agents (3.7%).Population-attributable fractions provide a valuable quantitative appraisal of the impact of different factors in cancer causation, and are thus helpful in prioritising cancer control strategies. However, quantifying the likely impact of preventive interventions requires rather complex scenario modelling, including specification of realistically achievable population distributions of risk factors, and the timescale of change, as well as the latent periods between exposure and outcome, and the rate of change following modification in exposure level. [ABSTRACT FROM AUTHOR]

There are several approaches for assessing nutrient enrichment impacts in marine waters including the OSPAR* Comprehensive Procedure, the TRIX* ranking process, the WFD, ASSETS* and EPA NCA*. They differ in definitions and application, but all use key indicators for evaluating eutrophication status. Data from two estuaries in the United Kingdom (UK) were used to test the hypothesis that these five methods would result in the same outcome. The intent is to provide managers with information for selecting an appropriate method, insight about how each method works, how results from different methods compare and a basis for improvement of methods. Results from all approaches indicate that both estuaries required management intervention, but detailed results differed. Methods using more than one biological indicator show that secondary biological impacts were minimal, with the exception of moderate macroalgal problems in the Medway. Comparison of final results was difficult due to differences in: timeframes of data analysis (seasonal versus annual), characteristics included in indicator metrics (concentration, spatial coverage, frequency of occurrence), and methods for combining indicators to determine eutrophication status. This comparison suggests that use of annual data, inclusion frequency of occurrence, spatial coverage and, secondary biological indicators in the index, and a multi-category rating scale results in a more representative assessment. [ABSTRACT FROM AUTHOR]

Background: A family history of prostate cancer (PrCa) is a strong risk factor for the disease, indicating that inherited factors are important in this disease. We previously estimated that about 2% of PrCa cases diagnosed ≤ 55 years harbour a BRCA2 mutation and PrCa among BRCA2 carriers has been shown to be more aggressive, with poorer survival.Methods: To further evaluate the role of BRCA2 in PrCa predisposition, we screened 1864 men with PrCa aged between 36 and 88 years. We analysed the BRCA2 gene using a novel high-throughput multiplex fluorescence heteroduplex detection system developed for the ABI3130xl genetic analyzer.Results: We identified 19 protein-truncating mutations, 3 in-frame deletions and 69 missense variants of uncertain significance (UV) in our sample set. All the carriers of truncating mutations developed PrCa at ≤ 65 years, with a prevalence of BRCA2 mutation of 1.20% for cases in this age group.Conclusion: Based on the estimated frequency of BRCA2 mutations in the United Kingdom we estimate that germline mutations in the BRCA2 gene confer an ∼ 8.6-fold increased risk of PrCa by age 65, corresponding to an absolute risk of ∼ 15% by age 65. These results suggest that routine testing of early onset PrCa cases for germline BRCA2 mutations will further help to refine the prevalence and risk associated with BRCA2 mutations and may be useful for guiding management options. [ABSTRACT FROM AUTHOR]

Background: This study reports awareness of the 'Open up to Mouth Cancer' campaign materials and oral cancer knowledge among two UK adult Bangladeshi communities, both at high risk for oral cancer.Methods: Differences in the outcomes of campaign awareness and knowledge of oral cancer risk factors and early signs were compared between campaign and comparison areas. Home-based interviews were conducted with representative samples from both areas by bilingual interviewers. Data collected included a modified 36-item Humphris Oral Cancer Knowledge Scale and socio-demographic information. The data were collected 4 weeks after the campaign completion and analysed using χ(2)-tests and binary logistic regressions.Results: The response rate was 77%. Both awareness of the campaign materials (29.99% (95% confidence interval (CI) 15.82, 46.99) vs 8.12% (95% CI 6.16, 10.62)) and the mean Humphris Oral Cancer Knowledge Scale scores (13.32 (95% CI 11.06, 15.57) vs 8.27 (95% CI 6.59, 9.94)) were higher in the campaign area. The campaign area sample was significantly more likely to be aware of the materials (odds ratio (OR)=6.03, 95% CI 3.00, 12.1).Conclusion: Superior awareness and oral cancer knowledge was identified in the community with access to the campaign materials. Further evaluation to identify long-term campaign impact is required. [ABSTRACT FROM AUTHOR]

Background: Evidence concerning the influence of ethnic diversity on clinical encounters in cancer care is sparse. We explored health providers' experiences in this context.Methods: Focus groups were conducted with a purposeful sample of 106 health professionals of differing disciplines, in 18 UK primary and secondary care settings. Qualitative data were analysed using constant comparison and processes for validation.Results: Communication and the quality of information exchanged with patients about cancer and their treatment was commonly frustrated within interpreter-mediated consultations, particularly those involving a family member. Relatives' approach to ownership of information and decision making could hinder assessment, informed consent and discussion of care with patients. This magnified the complexity of disclosing information sensitively and appropriately at the end of life. Professionals' concern to be patient-centred, and regard for patient choice and autonomy, were tested in these circumstances.Conclusion: Health professionals require better preparation to work effectively not only with trained interpreters, but also with the common reality of patients' families interpreting for patients, to improve quality of cancer care. Greater understanding of cultural and individual variations in concepts of disclosure, patient autonomy and patient-centredness is needed. The extent to which these concepts may be ethnocentric and lack universality deserves wider consideration. [ABSTRACT FROM AUTHOR]

Background: A recent systematic review and meta-analysis suggested that occupational exposure to endotoxins protects against lung cancer. To explore this hypothesis further, the follow-up of mortality of a cohort of 3551 workers, who were employed in the British cotton industry during 1966-1971, was extended by 23 years.Methods: Subjects had originally been recruited to a survey of respiratory disease, which collected information about occupation and smoking habits. Cumulative exposures to endotoxins were estimated from data on endotoxin levels by work areas in cotton mills. Risks of lung cancer were estimated using survival modelling.Results: During follow-up, 2018 deaths were recorded before the age of 90 years, including 128 deaths from lung cancer. After adjustment for smoking, hazard ratios (95% confidence intervals) for cumulative endotoxin exposures of ≤30,000, >30,000 and ≤200,000, >200,000 and ≤400,000, >400,000 and ≤600,000 and >600,000 endotoxin units (EU) m(-3) years were 1, 0.8 (0.5-1.6), 0.7 (0.4-1.3), 0.6 (0.3-1.0) and 0.5 (0.3-0.9), respectively (P for trend=0.005).Conclusion: Our findings strengthen the evidence that occupational exposure to endotoxins protects against lung cancer, and suggest that the effect depends on cumulative dose and persists after exposure ceases. [ABSTRACT FROM AUTHOR]

Background: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T.Methods: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity.Results: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype.Conclusion: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age. [ABSTRACT FROM AUTHOR]

Background: Brain tumours account for <2% of all primary neoplasms but are responsible for 7% of the years of life lost from cancer before age 70 years. The latest survival trends for patients with CNS malignancies have remained largely static. The objective of this study was to evaluate the change in practice as a result of implementing the Improving Outcomes Guidance from the UK National Institute for Health and Clinical Excellence (NICE).Methods: Patients were identified from the local cancer registry and hospital databases. We compared time from diagnosis to treatment, proportion of patients discussed at multidisciplinary team (MDT) meetings, treatment received, length of inpatient stay and survival. Inpatient and imaging costs were also estimated.Results: Service reconfiguration and implementation of NICE guidance resulted in significantly more patients being discussed by the MDT--increased from 66 to 87%, reduced emergency admission in favour of elective surgery, reduced median hospital stay from 8 to 4.5 days, increased use of post-operative MRI from 17 to 91% facilitating early discharge and treatment planning, and reduced cost of inpatient stay from £2096 in 2006 to £1316 in 2009. Patients treated with optimal surgery followed by radiotherapy with concomitant and adjuvant temozolomide achieved outcomes comparable to those reported in clinical trials: median overall survival 18 months (2-year survival 35%).Conclusions: Advancing the management of neuro-oncology patients by moving from an emergency-based system of patient referral and management to a more planned elective outpatient-based pattern of care improves patient experience and has the potential to deliver better outcomes and research opportunities. [ABSTRACT FROM AUTHOR]

Background: Hospital mastectomy rates vary. This study explores the relationship between mastectomy rates and breast cancer patients' consultation and decision-making experiences with specialist clinicians.Methods: Qualitative semi-structured interviews were conducted with 65 patients from three purposively selected breast units from a single UK region. Patients provided with a choice of breast cancer surgery (breast conservation therapy (BCT) or mastectomy) were purposively recruited from high, medium and low case-mix-adjusted mastectomy rate units.Results: Low mastectomy rate unit patients' consultation and decision-making experiences were markedly different to those of the medium and high mastectomy rate breast units. Treatment variation was associated with patients' perception of the most reassuring and least disruptive treatment; the content and style of information provision (equipoise or directed); level of patient participation in decision making; the time and process of decision making and patient autonomy in decision making. The provision of more comprehensive less directive information and greater autonomy, time and support of independent decision making were associated with a lower uptake of BCT.Conclusion: Variation in hospital mastectomy rates was associated with differences in the consultation and decision-making experiences of breast cancer patients. Higher mastectomy rates were associated with the facilitation of more informed autonomous patient decision making. [ABSTRACT FROM AUTHOR]

Background: Completeness of ascertainment is a very important aspect of cancer registration. There is no recent published estimate for childhood cancer in Britain.Methods: We estimated completeness of ascertainment by the National Registry of Childhood Tumours for cancer diagnosed under age 15 years in residents of Britain during 2003-04. Stratified two-source capture-recapture was applied to notifications from general cancer registries (CRs) and specialist clinicians. Variation in notification patterns was assessed by logistic regression. Results were verified by cross-checking with Hospital Episode Statistics for leukaemia patients from England born in 1998 and diagnosed before 2005.Results: CRs notified 92-96% of registrations, and specialist clinicians 93%. Notification patterns varied slightly according to registry region, age at diagnosis, diagnostic group, socioeconomic status, and whether the patient had died. Irrespective of stratification by these factors, the overall completeness estimate was 99-100% (assuming independence of sources). Estimated completeness was at least 99% within all subgroups, except for one region (Thames 98-99%) and two small diagnostic groups (germ-cell and gonadal cancer 98-99%, melanoma and non-skin cancer 97-98%).Interpretation: The independence assumption cannot be fully justified, as both sources used records from treatment centres. With this caveat, ascertainment of recently diagnosed childhood cancer in Britain appears to be virtually complete. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom NHS Breast Screening Programme was established in 1988, and women aged between 50 and 70 are routinely invited at three yearly intervals. Expected United Kingdom interval cancer rates have been calculated previously, but this is the first publication from an exercise to collate individual-based interval cancer data at a national level.Methods: Interval cancer case ascertainment is achieved by the regular exchange of data between Regional Breast Screening Quality Assurance Reference Centres and Cancer Registries. The present analysis includes interval cancers identified in women screened between 1st April 1997 and 31st March 2003, who were aged between 50 and 64 at the time of their last routine screen.Results: In the periods >0-<12 months, 12-<24 months and 24-<36 months after a negative screen, we found overall interval cancer rates and regional ranges of 0.55 (0.43-0.76), 1.13 (0.92-1.47) and 1.22 (0.93-1.57) per 1000 women screened, respectively. Rates in the period 33-<36 months showed a decline, possibly associated with early re-screening or delayed presentation.Conclusions: Interval cancer rates were higher than the expected rates in the 24-month period after a negative screen, but were similar to published results from other countries. Increases in background incidence may mean that the expected rates are underestimated. It is also possible that, as a result of incomplete case ascertainment, interval cancers rates were underestimated in some regions in which rates were less than the expected. [ABSTRACT FROM AUTHOR]

Background: We aimed to estimate and externally validate a new UK-specific prognostic model for predicting the long-term risk of a first recurrent event (local recurrence, metastatic recurrence, or second primary breast cancer) in women diagnosed with early breast cancer.Methods: Using data on the prognostic characteristics and outcomes of 1844 women treated for early breast cancer at the Churchill Hospital in Oxford, parametric regression-based survival analysis was used to estimate a prognostic model for recurrence-free survival. The model, which incorporated established prognostic factors, was externally validated using independent data. Its performance was compared with that of the Nottingham Prognostic Index (NPI) and Adjuvant! Online.Results: The number of positive axillary lymph nodes, tumour grade, tumour size and patient age were strong predictors of recurrence. Oestrogen receptor (ER) positivity was shown to afford a moderate protective effect. The model was able to separate patients into distinct prognostic groups, and predicted well at the patient level, mean Brier Accuracy Score=0.17 (s.e.=0.004) and overall C=0.745 (95% CI, 0.717-0.773). Its performance diminished only slightly when applied to a second independent data set. When compared with the NPI, the model was able to better discriminate between women with excellent and good prognoses, and it did not overestimate 10-year recurrence-free survival to the extent observed for Adjuvant! Online.Conclusion: The model estimated here predicts well at both the individual patient and group levels, and appears transportable to patients treated at other UK hospitals. Its parametric form permits long-term extrapolation giving it an advantage over other prognostic tools currently in use. A simple point scoring system and reference table allow 5-, 10-, and 15-year predictions from the model to be quickly and easily estimated. The model is also available to download as an interactive computer program. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent.Methods: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ).Results: Compared with individuals in the lightest category of drinkers (>0-<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5-<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15-<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30-<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with >or=45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results.Conclusion: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic inequalities in survival were observed for many cancers in England during 1981-1999. The NHS Cancer Plan (2000) aimed to improve survival and reduce these inequalities. This study examines trends in the deprivation gap in cancer survival after implementation of the Plan.Materials and Method: We examined relative survival among adults diagnosed with 1 of 21 common cancers in England during 1996-2006, followed up to 31 December 2007. Three periods were defined: 1996-2000 (before the Cancer Plan), 2001-2003 (initialisation) and 2004-2006 (implementation). We estimated the difference in survival between the most deprived and most affluent groups (deprivation gap) at 1 and 3 years after diagnosis, and the change in the deprivation gap both within and between these periods.Results: Survival improved for most cancers, but inequalities in survival were still wide for many cancers in 2006. Only the deprivation gap in 1-year survival narrowed slightly over time. A majority of the socioeconomic disparities in survival occurred soon after a cancer diagnosis, regardless of the cancer prognosis.Conclusion: The recently observed reduction in the deprivation gap was minor and limited to 1-year survival, suggesting that, so far, the Cancer Plan has little effect on those inequalities. Our findings highlight that earlier diagnosis and rapid access to optimal treatment should be ensured for all socioeconomic groups. [ABSTRACT FROM AUTHOR]

Background: Women's awareness of ovarian cancer (OC) risks, their attitudes towards and beliefs about screening, together with misunderstandings or gaps in knowledge, may influence screening uptake.Methods: In total, 21 715 post-menopausal women completed questionnaires before randomisation into the UK Collaborative Trial of Ovarian Cancer Screening.Results: In all, 42.3% correctly identified their lifetime risk of OC; 87.1% knew that a family history of OC increased risk, but only 26.7% appreciated the association with a family history of breast cancer. Although 38.2% acknowledged increased risk post-menopause, only 8.8% were aware that OC diagnoses are highest in women over 65 years. Few (13.7%) recognised the association between pregnancy and reduced OC risk or protective effects of breastfeeding (6.2%). There were common misconceptions; 37.2% thought that an abnormal cervical smear and 26.4% that oral contraception increased the likelihood of OC. Although 84.4% recognised that most ovarian masses are benign, 20.2% thought having had a benign cyst increased OC risk. Most (99.4%) believed that a high uptake of OC screening would reduce mortality and (96.2%) that screen-detected cancers would have an improved prognosis.Conclusions: The results show a need for improved public understanding about OC risks and provide important information for GPs and health educationalists about initiatives needed for future awareness, prevention and screening programmes. [ABSTRACT FROM AUTHOR]

Background: Prioritising control measures for occupationally related cancers should be evidence based. We estimated the current burden of cancer in Britain attributable to past occupational exposures for International Agency for Research on Cancer (IARC) group 1 (established) and 2A (probable) carcinogens.Methods: We calculated attributable fractions and numbers for cancer mortality and incidence using risk estimates from the literature and national data sources to estimate proportions exposed.Results: 5.3% (8019) cancer deaths were attributable to occupation in 2005 (men, 8.2% (6362); women, 2.3% (1657)). Attributable incidence estimates are 13 679 (4.0%) cancer registrations (men, 10 063 (5.7%); women, 3616 (2.2%)). Occupational attributable fractions are over 2% for mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma, larynx and stomach cancers. Asbestos, shift work, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, occupation as a painter or welder, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists each contribute 100 or more registrations. Industries and occupations with high cancer registrations include construction, metal working, personal and household services, mining, land transport, printing/publishing, retail/hotels/restaurants, public administration/defence, farming and several manufacturing sectors. 56% of cancer registrations in men are attributable to work in the construction industry (mainly mesotheliomas, lung, stomach, bladder and non-melanoma skin cancers) and 54% of cancer registrations in women are attributable to shift work (breast cancer).Conclusion: This project is the first to quantify in detail the burden of cancer and mortality due to occupation specifically for Britain. It highlights the impact of occupational exposures, together with the occupational circumstances and industrial areas where exposures to carcinogenic agents occurred in the past, on population cancer morbidity and mortality; this can be compared with the impact of other causes of cancer. Risk reduction strategies should focus on those workplaces where such exposures are still occurring. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is the most common malignancy of infancy but little is known about the aetiological factors associated with the development of this tumour. A number of epidemiological studies have previously examined the risk associated with paternal occupational exposures but most have involved small numbers of cases. Here we present results from a large, population-based, case-control study of subjects diagnosed over a period of more than 30 years and recorded in the national registry of childhood tumours in Great Britain.Methods: A case-control study of paternal occupational data for 2920 cases of neuroblastoma, born and diagnosed in Great Britain between 1962 and 1999 and recorded in the National Registry of Childhood Tumours, and 2920 controls from the general population matched on sex, date of birth and birth registration district. Paternal occupations at birth, of the case or control child, were grouped by inferred exposure using an occupational exposure classification scheme. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), for each of the 32 paternal occupational exposure groups.Results: Only paternal occupational exposure to leather was statistically significantly associated with neuroblastoma, OR=5.00 (95% CI 1.07-46.93). However, this association became non-significant on correction for multiple testing.Conclusion: Our findings do not support the hypothesis that paternal occupational exposure is an important aetiological factor for neuroblastoma. [ABSTRACT FROM AUTHOR]

Background: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status.Methods: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received.Results: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity.Conclusions: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men. [ABSTRACT FROM AUTHOR]

This study compared nutrient intakes from 7-day menus for the US MyPlate and DASH Eating Plan versus the cutoff points for green lights defined by the UK's multiple traffic light (MTL) scheme. For both diets, the foods achieved green lights for saturated fat and salt, and for beverages for total fat, saturated fat and salt. The other nutrients achieved amber lights but were within the range of the two diets. By contrast, the MTL threshold for salt in beverages was outside the range of the diets. The values for salt in beverages in the MyPlate and Dash diet plans were 0.06±0.07 and 0.19±0.01 (s.d.) g/100 ml, which are both considerably lower compared with the cutoff of 0.3 g/100 ml for an MTL green light. Adjusting the green MTL threshold values to the median values for a healthful diet could help make MTL labelling a more valid way of helping consumers choose a healthful diet. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods: We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results: Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, 'misdiagnosis' occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion: Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. [ABSTRACT FROM AUTHOR]

Background: The National Health Service (NHS) bowel cancer screening programme (BCSP) was initiated across England in April 2006. To determine the feasibility of using national cancer registration data to assess the impact of the BCSP on stage-specific incidence, we studied trends in the incidence rates of colon (ICD10 C18) and rectosigmoid junction and rectum (ICD10 C19-C20) cancers and the completeness of data on Dukes stage in England.Methods: Data were obtained from all nine cancer registries for the period 1996-2004, before the introduction of the BCSP, in men and women aged 50-79 years.Results: Overall, incidence rates declined by 1% per year in the 9 years before the introduction of the BCSP (P<0.001). Dukes stage was recorded for 60% of all registrations but this varied between regions and over time. Only four registries had completeness of 74% or more. Registrations with unknown Dukes stage decreased from 1996 to 2000, and then increased during 2001-2004 affecting trends in stage-specific incidence.Conclusion: To study the impact of the BCSP on stage-specific incidence, regional variations in data completeness need to be addressed. [ABSTRACT FROM AUTHOR]

Background: Adjuvant! Online is an internet-based computer programme providing 10-year prognosis predictions for early breast cancer patients. It was developed in the United States, has been successfully validated in Canada, and is used in the United Kingdom and elsewhere. This study investigates the performance of Adjuvant! in a cohort of patients from the United Kingdom.Methods: Data on the prognostic factors and management of 1065 women with early breast cancer diagnosed consecutively at the Churchill Hospital in Oxford between 1986 and 1996 were entered into Adjuvant! to generate predictions of overall survival (OS), breast cancer-specific survival (BCSS), and event-free survival (EFS) at 10 years. Such predictions were compared with the observed 10-year outcomes of these patients.Results: For the whole cohort, Adjuvant! significantly overestimated OS (by 5.54%, P<0.001), BCSS (by 4.53%, P<0.001), and EFS (by 3.51%, P=0.001). For OS and BCSS, overestimation persisted across most demographic, pathologic, and treatment subgroups investigated. Differences between Adjuvant! predicted and observed EFS appeared smaller, and were significant for far fewer subgroups, only 5 out of the 28. The likely explanation for such discordance is that US breast cancer mortality rates (upon which Adjuvant! is based) appear to be systematically lower than breast cancer mortality rates in the United Kingdom. Differences in survival after recurrence would seem to be one contributory factor, with data suggesting that prognosis after relapse appears poorer in the United Kingdom. This may reflect the fact that new and more effective cancer drugs are often only approved for use in the United Kingdom many years after their adoption in the United States.Conclusion: The use of Adjuvant! by clinicians within the UK National Health Service is increasing, under the assumption that the programme is transferrable to the United Kingdom. At least for women treated for breast cancer at the Churchill Hospital in Oxford, however, Adjuvant!'s predictions were on the whole overoptimistic. If the findings reported here could be shown to be generalisable to other areas of the United Kingdom, then thought should perhaps be given to the development of a UK-specific version of the programme. [ABSTRACT FROM AUTHOR]

Background: Few prospective studies have examined cancer incidence among vegetarians.Methods: We studied 61,566 British men and women, comprising 32,403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20,601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use.Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07-1.20) in fish eaters and 0.36 (0.16-0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18-0.77) in fish eaters and 0.69 (0.45-1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36-1.81) in fish eaters and 0.47 (0.25-0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56-1.29) in fish eaters and 0.55 (0.39-0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73-0.93) in fish eaters and 0.88 (0.81-0.96) in vegetarians (P for heterogeneity=0.001).Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters. [ABSTRACT FROM AUTHOR]

Background:The use of minimally invasive ablative therapies in localised prostate cancer offer potential for a middle ground between active surveillance and radical therapy.Methods:An analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between 1 February 2005 and 15 May 2007 was carried out in two centres. Outcome data (side-effects using validated patient questionnaires, biochemical, histology) were evaluated.Results:A total of 172 men were treated under general anaesthetic as day-case procedures with 78% discharged a mean 5 h after treatment. Mean follow-up was 346 days (range 135–759 days). Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs 40.4%, P=0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172) with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae. In all, 78.3% achieved a PSA nadir 0.5 μg ml−1 at 12 months, with 57.8% achieving 0.2 μg ml−1. Then, 8 out of 13 were retreated with HIFU, one had salvage external beam radiotherapy and four chose active surveillance for small-volume low-risk disease. Overall, there was no evidence of disease (PSA <0.5 μg ml−1 or negative biopsy if nadir not achieved) after one HIFU session in 92.4% (159 out of 172) of patients.Conclusion:HIFU is a minimally invasive, day-case ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Long-term outcome needs further evaluation and the inception of an international registry for cases treated using HIFU will significantly aid this health technology assessment.British Journal of Cancer (2009) 101, 19–26; doi:10.1038/sj.bjc.6605116 www.bjcancer.com Published online online 9 June 2009 [ABSTRACT FROM AUTHOR]

Background: The human death-associated protein 3 (hDAP3) is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a pro-apoptotic function.Methods: A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene. The promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence. The mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents.Results: The study revealed nine transcription factors presenting enriched motifs for these gene promoters, five of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and four in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), GABPA, PPARG-RXRA and estrogen-related receptor alpha (ESRRA)). An independent microarray data set showed the overexpression of ELK1, RUNX1 and ESRRA in the thyroid oncocytic tumours. Exploring the thyroid tumours, we found that DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue. ELK1 and ESRRA were also showed upregulated with DAP3.Conclusion: ELK1 and ESRRA may be considered as potential regulators of the DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis. [ABSTRACT FROM AUTHOR]

Background: Epigenetic silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) by promoter methylation is associated with improved survival in glioblastomas treated with alkylating agents. In this study, we investigated MGMT promoter methylation in glioblastomas treated with temozolomide and radiotherapy in a single UK treatment centre.Methods: Quantitative methylation data at individual CpG sites were obtained by pyrosequencing for 109 glioblastomas.Results: Median overall survival (OS) was 12.4 months with 2-year survival of 17.9%. Pyrosequencing data were reproducible with archival samples yielding data for all glioblastomas. Variation in methylation patterns of discrete CpG sites and intratumoral methylation heterogeneity were observed. A total of 58 out of 109 glioblastomas showed average methylation >non-neoplastic brain in at least one clinical sample; 86% had homogeneous methylation status in multiple samples. Methylation was an independent prognostic factor associated with prolonged progression-free survival (PFS) and OS. Cases with methylation more than 35% had the longest survival (median PFS 19.2; OS 26.2 months, 2-year survival of 59.7%). Significant differences in PFS were seen between those with intermediate or high methylation and unmethylated cases, whereas cases with low, intermediate or high methylation all showed significantly different OS.Conclusions: These data indicate that MGMT methylation is prognostically significant in glioblastomas given chemoradiotherapy in the routine clinic; furthermore, the extent of methylation may be used to provide additional prognostic stratification. [ABSTRACT FROM AUTHOR]

Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in approximately 1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P(dominant)=0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case-control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80-0.99) and remained statistically significant (P(dominant)=0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC. [ABSTRACT FROM AUTHOR]

Little is known about how reproductive factors affect the risk of breast cancers of different histology. In an analysis of prospective data on 1.2 million middle-aged UK women, we used proportional hazards models to estimate the relative risks of six histological types in relation to menarche, childbearing and menopause. During 8.7 million person-years of follow-up, 17 923 ductal, 3332 lobular, 1062 tubular, 944 mixed ductal lobular, 330 mucinous and 117 medullary cancers were diagnosed. The effect of both age at menarche and age at first birth was greatest for lobular tumours; relative risks per 5-year increase in age at menarche for ductal, lobular, and tubular cancers were 0.93 (0.87-0.99), 0.65 (0.56-0.76), and 0.75 (0.57-0.98), respectively (P-value for heterogeneity=0.0001); and the relative risks per 5-year increase in age at first birth were 1.10 (1.07-1.12), 1.23 (1.17-1.29), and 1.13 (1.03-1.23), respectively (P-value for heterogeneity=0.0006). Increasing parity reduced the risk of each tumour type, except medullary cancers, but the reduction in risk was greater for mucinous cancers than for any other subtype considered (P<0.05 for comparison with each other subtype in turn). The effect of menopause did not vary significantly by tumour histology. Meta-analysis of published results on the effects of age at menarche and age at first birth on ductal and lobular cancers were in keeping with our findings. [ABSTRACT FROM AUTHOR]

We present the preliminary toxicity data from the MRC COIN trial, a phase III randomised controlled trial of first-line therapy in advanced colorectal cancer, with particular reference to the addition of cetuximab to an oxaliplatin-fluoropyrimidine combination. A total of 804 patients were randomised between March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5-fluorouracil (5FU) or capecitabine) was decided by the treating physician and patient before randomisation. Toxicity data were collected from all patients. Two hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333 oxaliplatin+capecitabine (Xelox, 41%), 102 received OxMdG+cetuximab (OxMdG+C, 13%) and 166 Xelox+cetuximab (21%). Percent grade 3/4 toxicities included diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox, OxMdG+C and Xelox+C, respectively. Sixty-day all-cause mortality was 6, 5, 5 and 7%. Statistically significant differences were evident for patients receiving Xelox+cetuximab vs Xelox alone: diarrhoea relative risk (RR) 1.69 (1.17, 2.43, P=0.005) and nausea/vomiting RR 2.01 (1.16, 3.47, P=0.012). The excess toxicity observed in the oxaliplatin-, capecitabine-, cetuximab-treated patients led the trial management group to conclude that a capecitabine dose adjustment was required to maintain safety levels when using this regimen. [ABSTRACT FROM AUTHOR]

A comparative study was performed to evaluate the performance of the UK Met Office’s Global Seasonal (GloSea) prediction General Circulation Model (GCM) for the forecast of maximum surface air temperature (Tmax) over the Indian region using the model generated hindcast of 15-members ensemble for 16 years (1987–2002). Each hindcast starts from 1st January and extends for a period of six months in each year. The model hindcast Tmax is compared with Tmax obtained from verification analysis during the hot weather season on monthly and seasonal scales from March to June. The monthly and seasonal model hindcast climatology of Tmax from 240 members during March to June and the corresponding observed climatology show highly significant (above 99.9% level) correlation coefficients (CC) although the hindcast Tmax is over-estimated (warm bias) over most parts of the Indian region. At the station level over New Delhi, although the forecast error (forecast-observed) at the monthly scale gradually increases from March to June, the forecast error at the seasonal scale during March to May (MAM) is found to be just 1.67 °C. The GloSea model also simulates well Tmax anomalies on monthly and seasonal scales during March to June with the lower Root Mean Square Error (RMSE) of bias corrected forecast (less than 1.2 °C), which is much less than the corresponding RMSE of climatology (reference) forecast. The anomaly CCs (ACCs) over the station in New Delhi are also highly significant (above 95% level) on monthly to seasonal time scales from March to June, except for April. The skill of the GloSea model for the seasonal forecast of Tmax as measured from the ACC map and the bias corrected RMSE map is reasonably good during MAM and April to June (AMJ) with higher ACC (significant at 95% level) and lower RMSE (less than 1.5 °C) found over many parts of the Indian regions. [ABSTRACT FROM AUTHOR]

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m(-2) to 60 mg m(-2) to 70 mg m(-2) to identify the maximum tolerated dose (60 mg m(-2)). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m(-2) per day) for 5 weeks. Irinotecan (60 mg m(-2)) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity. [ABSTRACT FROM AUTHOR]