FIT for the future: a case for risk-based colorectal cancer screening using the faecal immunochemical test.

Worldwide, the guaiac faecal occult blood test (gFOBT) is being replaced with the more accurate faecal immunochemical test (FIT) for colorectal cancer (CRC) screening. From January 2016, the National Screening Committee in the UK has recommended a change from the gFOBT to the FIT following a successful Bowel Cancer Screening Programme pilot study with over 40 000 participants. Although the test has shown improved uptake and the ability to detect significantly more colorectal cancers and advanced adenomas, the higher uptake and test positivity will challenge the capacity of colonoscopy services. One of the main advantages of the FIT is that it provides a quantitative haemoglobin concentration which has been shown to relate to the risk of CRC. Risk scoring systems which combine the FIT concentration with risk factor assessment have been shown to improve the sensitivity of the test. This individualized approach to screening could enable those at greatest risk to be referred for colonoscopy, optimizing resource use and ultimately patient outcomes.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Faecal occult blood testing.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on faecal occult blood testing includes 21 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.

Socioeconomic variation in uptake of colonoscopy following a positive faecal occult blood test result: a retrospective analysis of the NHS Bowel Cancer Screening Programme.

BACKGROUND: Bowel cancer is a serious health burden and its early diagnosis improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals with a positive test result. Socioeconomic inequalities have been demonstrated for FOBt uptake, but it is not known whether they persist at the next stage of the screening pathway. The aim of this study was to assess the association between colonoscopy uptake and area socioeconomic deprivation, controlling for individual age and sex, and area ethnic diversity, population density, poor self-assessed health, and region. METHODS: Logistic regression analysis of colonoscopy uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged between 60 and 69 years. RESULTS: Overall colonoscopy uptake was 88.4%. Statistically significant variation in uptake is found between quintiles of area deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9-89.1%), quintiles of poor self-assessed health (87.5-89.5%), non-white ethnicity (84.6-90.6%) and population density (87.9-89.3%), and geographical regions (86.4-90%). CONCLUSION: Colonoscopy uptake is high. The variation in uptake by socioeconomic deprivation is small, as is variation by subgroups of age and sex, poor self-assessed health, ethnic diversity, population density, and region.

The impact of media coverage of the Flexible Sigmoidoscopy Trial on English colorectal screening uptake.

OBJECTIVE: To assess the impact of media coverage of the UK Flexible Sigmoidoscopy Trial on colorectal screening uptake in England. SETTING: In April 2010, publication of the UK Flexible Sigmoidoscopy (FS) Trial results generated considerable media interest in both FS and colorectal cancer (CRC) generally. METHODS: We used routinely collected data from the south of England (excluding London) to analyse return of faecal occult blood test (FOBt) kits within 28 days of the invitation (early uptake) among 60-69 year olds, before (T1, n = 31,229), around the time of (T2, n = 39,571), and one month after (T3, n = 33,430) the FS publicity. RESULTS: FOBt uptake over the whole period was 58.2%, with 38.4% of the kits returned within 28 days (early uptake). Across the three time periods, early uptake was 35.8% at T1, 39.4% at T2, and 39.7% at T3. Multivariate regression controlling for age, gender and socioeconomic status confirmed that uptake was higher if people received the FOBt kit around the time of the media coverage (T2: odds ratio [OR] = 1.17, 95% CI = 1.13-1.20), or one month after (T3: OR = 1.18, 95% CI = 1.15-1.22) than before (T1). Sub-group analyses demonstrated that the impact was stronger among previous non-responders than among first-time invitees or previous responders (P < 0.001). CONCLUSION: Media coverage of the FS Trial appeared to have a small but positive impact on FOBt screening uptake, especially among people who had previously abstained from screening.

Primary care endorsement letter and a patient leaflet to improve participation in colorectal cancer screening: results of a factorial randomised trial.

BACKGROUND: The trial aimed to investigate whether a general practitioner's (GP) letter encouraging participation and a more explicit leaflet explaining how to complete faecal occult blood test (FOBT) included with the England Bowel Cancer Screening Programme invitation materials would improve uptake. METHODS: A randomised controlled 2 × 2 factorial trial was conducted in the south of England. Overall, 1288 patients registered with 20 GPs invited for screening in October 2009 participated in the trial. Participants were randomised to either a GP's endorsement letter and/or an enhanced information leaflet with their FOBT kit. The primary outcome was verified with return of the test kit within 20 weeks. RESULTS: Both the GP's endorsement letter and the enhanced procedural leaflet, each increased participation by ∼6% - the GP's letter by 5.8% (95% CI: 4.1-7.8%) and the leaflet by 6.0% (95% CI: 4.3-8.1%). On the basis of the intention-to-treat analysis, the random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP's letter and 1.12 (P=0.029) for the leaflet. In the absence of an interaction, an additive effect for receiving both the GP's letter and leaflet (11.8%, 95% CI: 8.5-16%) was confirmed. The per-protocol analysis indicated that the insertion of an electronic GP's signature on the endorsement letter was associated with increased participation (P=0.039). CONCLUSION: Including both an endorsement letter from each patient's GP and a more explicit procedural leaflet could increase participation in the English Bowel Cancer Screening Programme by ∼10%, a relative improvement of 20% on current performance.

Evaluation of a paired creatine kinase test for the diagnosis of acute myocardial infarction in patients with a non-diagnostic electrocardiogram.

OBJECTIVE: The rate of rise of total plasma creatine kinase (CK) activity in the first 12 hours from presentation can be used to diagnose acute myocardial infarction. The aim of this study was to evaluate the performance of an abbreviated form of this test in the diagnosis of acute myocardial infarction in patients in whom the initial electrocardiogram was inconclusive. METHODS: Using a protocol that requires only two CK measurements (separated by four hours) to estimate the rate of rise, the performance of the test was investigated using data accrued from 345 consecutive admissions with suspected acute myocardial infarction. RESULTS: A CK increment (delta CK) of > 20% in the first four hours from presentation had a diagnostic sensitivity of 84.4% (95% confidence interval 75.5 to 93.3), specificity of 85.8% (80.1 to 91.5), positive predictive accuracy of 73.0% (62.9 to 83.1), and negative predictive accuracy of 92.4% (87.9 to 96.9). Using more stringent diagnostic criteria (delta CK > 20% and 4 h CK value > 160 U/litre) resulted in an increase in specificity and positive predictive accuracy to 96.5% and 91.1% respectively, and a small reduction in sensitivity and negative predictive accuracy to 79.7% and 91.3%, respectively, 94% of all infarcts were correctly identified using the ECG as the initial investigation and paired CK measurement as an additional test when this was inconclusive. In the 44 patients who received thrombolysis on the basis of an early biochemical diagnosis of acute myocardial infarction, the median time delay (75th centile) to thrombolysis was 10.75 (SD 15.0) hours. CONCLUSIONS: When the presenting ECG is non-diagnostic, sequential sampling of cardiac enzymes is a feasible alternative in the early diagnosis of patients with suspected myocardial infarction, even in the emergency setting. Further studies are required to define the optimal biochemical assay and timed sampling protocol.

Diagnostic significance of octadeca-9,11-dienoic acid in cervical neoplasia.

The percentage molar ratio (%MR) of the 9,11 and 9,12 isomers of octadecadienoic acid was determined in cervical exfoliated cells from 148 subjects, of whom 27 had cytologically proven intraepithelial neoplasia and in cervical biopsy specimens from 43 subjects, of whom 24 had histologically diagnosed cervical intraepithelial neoplasia. The %MR in both cervical biopsy specimens and exfoliated cells did not significantly differ in subjects with or without cervical intraepithelial neoplasia. The measurement of the %MR of 9,11:9,12 octadecadienoic acid has no role in the detection of cervical intraepithelial neoplasia.

Effects of the drug Disulphine Blue on routine biochemical investigations.

Major interference by Disulphine Blue in the colorimetric determination of amylase, albumin, protein, iron and total iron-binding capacity is described. The drug, an intense blue dye, was administered intravenously to a patient before surgery to allow demarcation of devitalised bone. Successive sampling showed the drug to have a half-life of 30 hours, to remain visible for 150 hours in both urine and blood, and to cause significant interference with the five analytes for up to 21/2 days. The 640 nm absorbance peak of Disulphine Blue was shown to be pH-dependent, and therefore the reaction conditions of individual methods may influence the degree of interference.

Free-radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis.

Free-radical oxidation (peroxidation) products were measured in (a) 65 synovial effusions and (b) 30 sera from normal subjects and 58 sera from patients with rheumatoid arthritis (RA). Free-radical oxidation products were detectable in 90% of synovial fluids, their concentration being higher in "inflammatory" than in "degenerative" joint disease. Free-radical oxidation products in serum were significantly elevated in patients with RA compared to normal controls; the levels declined after treatment with a variety of antiinflammatory agents.