Multi-model attribution of upper-ocean temperature changes using an isothermal approach

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An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme

© 2014 Massat et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Identification of Mendelian inconsistencies between SNP and pedigree information of sibs

Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype information are not in agreement. Methods Straightforward tests to detect Mendelian inconsistencies exist that count the number of opposing homozygous marker (e.g. SNP) genotypes between parent and offspring (PAR-OFF). Here, we develop two tests to identify Mendelian inconsistencies between sibs. The first test counts SNP with opposing homozygous genotypes between sib pairs (SIBCOUNT). The second test compares pedigree and SNP-based relationships (SIBREL). All tests iteratively remove animals based on decreasing numbers of inconsistent parents and offspring or sibs. The PAR-OFF test, followed by either SIB test, was applied to a dataset comprising 2,078 genotyped cows and 211 genotyped sires. Theoretical expectations for distributions of test statistics of all three tests were calculated and compared to empirically derived values. Type I and II error rates were calculated after applying the tests to the edited data, while Mendelian inconsistencies were introduced by permuting pedigree against genotype data for various proportions of animals. Results Both SIB tests identified animal pairs for which pedigree and genomic relationships could be considered as inconsistent by visual inspection of a scatter plot of pairwise pedigree and SNP-based relationships. After removal of 235 animals with the PAR-OFF test, SIBCOUNT (SIBREL) identified 18 (22) additional inconsistent animals. Seventeen animals were identified by both methods. The numbers of incorrectly deleted animals (Type I error), were equally low for both methods, while the numbers of incorrectly non-deleted animals (Type II error), were considerably higher for SIBREL compared to SIBCOUNT. Conclusions Tests to remove Mendelian inconsistencies between sibs should be preceded by a test for parent-offspring inconsistencies. This parent-offspring test should not only consider parent-offspring pairs based on pedigree data, but also those based on SNP information. Both SIB tests could identify pairs of sibs with Mendelian inconsistencies. Based on type I and II error rates, counting opposing homozygotes between sibs (SIBCOUNT) appears slightly more precise than comparing genomic and pedigree relationships (SIBREL) to detect Mendelian inconsistencies between sib

Colorectal cancer screening using the faecal occult blood test (FOBt): a survey of GP attitudes and practices in the UK

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the third most common cancer in the UK. Five-year survival rates are less than 50%, largely because of late diagnosis. Screening using faecal occult blood tests (FOBt) can detect bowel cancer at an earlier stage than symptomatic presentation, and has the potential to significantly decrease colorectal cancer mortality. However, uptake of screening is currently low, despite the introduction of the NHS Bowel Cancer Screening Programme (NHSBCSP), and it has been suggested that GP recommendations of screening can improve patient compliance. GP recommendation of CRC screening is argued to be affected by attitudes towards it, along with perceptions of its efficacy.</p> <p>Methods</p> <p>This paper presents the findings of a cross-sectional postal survey of GPs in the UK which aimed to investigate GPs' attitudes in relation to colorectal cancer screening and the use of FOBt in routine practice. An 'attitude' score was calculated, and binary logistic regression used to evaluate the association of socio-demographic and general practice attributes with attitudes towards CRC screening and FOBt.</p> <p>Results</p> <p>Of 3,191 GPs surveyed, 960 returned usable responses (response rate 30.7%). Positive attitudes were associated with personal experience of CRC screening and Asian or Asian British ethnicity. GPs from practices located in more deprived locations were also more likely to have positive attitudes towards FOBt and its recommendation to patients.</p> <p>Conclusions</p> <p>The success of population-based screening for CRC will largely be determined by GP attitudes and support, particularly with regard to FOBt. Previous research has implied that South Asian GPs are more likely to have negative attitudes towards FOBt screening, however, our research suggests that this is not a group requiring targeted interventions to increase their support for the NHSBCSP. Of the available CRC screening tests, GPs perceived FOBt to be the most appropriate for population-based screening.</p

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845

Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis.

Background: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. Methods: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. Findings: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. Interpretation: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. Funding: NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation

Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis

Background: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. Methods: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. Findings: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. Interpretation: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. Funding: NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation

Role of the general practitioner during the active breast cancer treatment phase: an analysis of health care use

PURPOSE: Little is known about the actual involvement of the general practitioner (GP) during the active breast cancer treatment phase. Therefore, this study explored (disease-specific) primary health care use among women undergoing active treatment for breast cancer compared with women without breast cancer. METHODS: A total of 185 women with a first diagnosis of early-stage breast cancer between 1998 and 2007 were identified in the primary care database of the Registration Network Groningen and matched with a reference population of 548 women without breast cancer on birth year and GP. RESULTS: Since diagnosis, patients with breast cancer had twice as many face-to-face contacts compared with women from the reference population (median 6.0 vs 3.0/year, Mann-Whitney (M-W) test p < 0.001). The median number of drug prescriptions and referrals was also significantly higher among patients than among the reference population (11.0 vs 7.0/year, M-W test p < 0.001 and 1.0 vs 0.0/year, M-W test p < 0.001). More patients than women from the reference population had face-to-face contacts or were prescribed drugs for reasons related to breast cancer and its treatment, including gastrointestinal problems, psychological reasons and endocrine therapy. CONCLUSIONS: During the active breast cancer treatment phase, GPs are involved in the management of treatment-related side effects and psychological symptoms, as well as in the administration of endocrine therapy. Based on the findings of this study, interventions across the primary/secondary interface can be planned to improve quality of life and other outcomes in patients undergoing breast cancer treatment

Follow-up care for men with prostate cancer and the role of primary care: a systematic review of international guidelines

The optimal role for primary care in providing follow-up for men with prostate cancer is uncertain. A systematic review of international guidelines was undertaken to help identify key elements of existing models of follow-up care to establish a theoretical basis for evaluating future complex interventions. Many guidelines provide insufficient information to judge the reliability of the recommendations. Although the PSA test remains the cornerstone of follow-up, the diversity of recommendations on the provision of follow-up care reflects the current lack of research evidence on which to base firm conclusions. The review highlights the importance of transparent guideline development procedures and the need for robust primary research to inform future evidence-based models of follow-up care for men with prostate cancer