Scottish Bowel Screening Programme colonoscopy quality - scope for improvement?

AIM: The delivery of the Scottish Bowel Screening Programme (SBoSP) is rooted in the provision of a high quality, effective and participant-centred service. Safe and effective colonoscopy forms an integral part of the process. Additional accreditation as part of a multi-faceted programme for participating colonoscopists, as in England, does not exist in Scotland. This study aimed to describe the quality of colonoscopy in the SBoSP and compare this to the English national screening standards. METHODS: Data were collected from the SBoSP between 2007 and 2014. End-points for analysis were caecal intubation, cancer, polyp and adenoma detection, and complications. Overall results were compared with 2012 published English national standards for screening and outcomes from 2006 to 2009. RESULTS: During the study period 53 332 participants attended for colonoscopy. The colonoscopy completion rate was 95.6% overall. The mean cancer detection rate was 7.1%, the polyp detection rate was 45.7% and the adenoma detection rate was 35.5%. The overall complication rate was 0.47%. CONCLUSION: Colonoscopy quality in the SBoSP has exceeded the standard set for screening colonoscopy in England, despite not adopting a multi-faceted programme for screening colonoscopy. However, the overall adenoma detection rate in Scotland was 9.1% lower than that in England which has implications for colonoscopy quality and may have an impact on cancer prevention rates, a key aim of the SBoSP.

Participation in bowel screening among men attending abdominal aortic aneurysm screening.

BACKGROUND: Uptake of population-based screening for colorectal cancer in Scotland is around 55 per cent. Abdominal aortic aneurysm (AAA) screening has recently been introduced for men aged 65 years and the reported uptake is 78 per cent. The aim was to determine the impact of a brief intervention on bowel screening in men who attended AAA screening, but previously failed to complete bowel screening. METHODS: Men invited for AAA screening between September 2015 and March 2016 within NHS Tayside were included. Attendees who had not responded to their latest bowel screening invitation were seen by a colorectal cancer clinical nurse specialist. Reasons for not completing the faecal occult blood test (FOBT) were recorded; brief information on colorectal cancer screening was communicated, and participants were offered a further invitation to complete a FOBT. Those who responded positively were sent a further FOBT from the Scottish Bowel Screening Centre. Subsequent return of a completed FOBT within 6 months was recorded. RESULTS: A total of 556 men were invited for AAA screening, of whom 38·1 per cent had not completed a recent FOBT. The primary reason stated for not participating was the time taken to complete the test or forgetting it (35·1 per cent). Other reasons included: lack of motivation (23·4 per cent), confusion regarding the aim of screening (16·2 per cent), disgust (19·8 per cent), fear (6·3 per cent) and other health problems (9·9 per cent). Following discussion, 81·1 per cent agreed to complete the FOBT and 49 per cent subsequently returned the test. CONCLUSION: A substantial proportion of previous bowel screening non-responders subsequently returned a completed FOBT following a brief intervention with a nurse specialist. Attendance at non-bowel screening appointments may provide a valuable opportunity to improve bowel screening uptake.

Patterns of uptake in a biennial faecal occult blood test screening programme for colorectal cancer.

AIM: The patterns of response in faecal occult blood test (FOBT) screening were studied. METHOD: A total of 251,578 people invited three times for faecal occult blood testing were categorized according to how they responded to the invitations, as follows: YNN, NYN, NNY, NYY, YNY, YYN, YYY or NNN (Y = response; N = no response). RESULTS: Overall, 163,038 (64.8%) responded at least once, and of those the biggest category was YYY (98,494, 60.4%). Of 1927 cancers diagnosed in the age group eligible for screening, there were 405 screen-detected cancers, 529 interval cancers and 993 cancers arising in people who had not been screened for over 2 years (i.e. falling outside the interval cancer category). In the YYY group, 79 screen-detected cancers would have been missed had the members of this group responded YNN and 65 had they responded YYN. In the YYN group, 104 screening cancers would have been missed if they had followed the YNN pattern. In most cases, the screen-detected cancers were diagnosed at the last invitation accepted, indicating that, after a diagnosis of cancer, further screening invitations were rarely accepted. Accordingly, the numbers of screen-detected and interval cancers were adjusted for likely pattern of response according to the proportion of the whole population falling into each pattern. With this adjustment, 40.9% of the cancers in the YYY group were screen detected compared with 29.3% in the YYN group and 20.7% in the YNN group (P < 0.001). Among those who responded once, twice and three times, the stage distribution of screen-detected cancers was similar, indicating that the prognosis of screen-detected cancer is unlikely to be poorer if not detected at the first screen. CONCLUSION: This study is the first to examine patterns of response to screening invitations and confirms the importance to individuals of continuing to accept repeated screening invitations.

Low faecal haemoglobin concentration potentially rules out significant colorectal disease.

AIM: The study aimed to determine whether faecal haemoglobin (Hb) concentration can assist in deciding who with lower abdominal symptoms will benefit from endoscopy. METHOD: Faecal Hb concentrations were measured on single samples from 280 patients referred for lower gastrointestinal tract endoscopy from primary care in NHS Tayside who completed a faecal immunochemical test (FIT) for Hb and underwent subsequent endoscopy. RESULTS: Among 739 invited patients, FIT and endoscopy were completed by 280 (median age 63 (18-84) years; 59.6% women), with a median time between FIT and endoscopy of 9 days. Six (2.1%) participants had cancer, 23 (8.2%) had high-risk adenoma (HRA) (more than three adenomas or any > 1 cm), 31 (11.1%) low-risk adenoma (LRA) and 26 (9.3%) inflammatory bowel disease (IBD) as the most serious diagnosis. Those with cancer had a median faecal Hb of > 1000 ng Hb/ml buffer. Those with cancer + HRA + IBD had a median faecal Hb concentration of 75 ng Hb/ml buffer (95% CI 18-204), which was significantly higher than that of all remaining participants without significant colorectal disease (P < 0.0001). Using a cut-off faecal Hb concentration of 50 ng Hb/ml buffer, negative predictive values of 100.0%, 94.4%, 93.4% and 93.9% were found for cancer, HRA, LRA and IBD. Patients with reasons for referral other than rectal bleeding and family history did not have high faecal Hb concentrations. CONCLUSION: Faecal Hb concentration measurements have considerable potential to contribute to reducing unnecessary endoscopy for the majority of symptomatic patients.

The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study.

BACKGROUND: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. METHODS: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000-2007) before the roll out of a national programme. All residents (50-69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. RESULTS: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83-0.99) overall and 0.73 (95% CI 0.65-0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06-1.38). CONCLUSION: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.

Negative screening colonoscopy after a positive guaiac faecal occult blood test: not a contraindication to continued screening.

AIM: In guaiac faecal occult blood test (gFOBT) screening at least 50% of positive individuals will have a colonoscopy negative for colorectal neoplasia. The question of continuing screening in this group has not been addressed. METHOD: Data on participants aged 50-69 years with a positive gFOBT result and a negative colonoscopy were followed through the biennial screening pilot conducted between 2000 and 2007 in Scotland. RESULTS: In the first screening round, 1527 colonoscopies were negative for neoplasia. 1300 were re-invited in the second round, 905 accepted, and 157 had a positive gFOBT result, giving a positivity rate of 17.4%. Colonoscopy revealed 20 subjects with adenoma and six with invasive cancer. In the third screening round 1031 were invited for a third time and 730 accepted: 55 had a positive gFOBT test, giving a positivity rate of 7.5%. In this group, six colonoscopies revealed adenomas but there were no cancers diagnosed. In the third screening round, 108 individuals had had two positive gFOBT results and two subsequent negative colonoscopies. Eighty-four were invited for a third gFOBT, 66 accepted and 19 (25.6%) had a positive result none of whom had an adenoma or carcinoma. CONCLUSION: These data indicate that a negative colonoscopy following a positive gFOBT is not a contraindication for further screening, although this is likely to have a low yield of neoplastic pathology after two negative colonoscopies.

Interval cancers in a FOBT-based colorectal cancer population screening programme: implications for stage, gender and tumour site.

BACKGROUND: Between 2000 and 2007, a demonstration pilot of biennial guaiac faecal occult blood test (GFOBT) screening was carried out in Scotland. METHODS: Interval cancers were defined as cancers diagnosed within 2 years (ie, a complete screening round) of a negative GFOBT. The stage and outcome of the interval cancers were compared with those arising contemporaneously in the non-screened Scottish population. In addition, the gender and site distributions of the interval cancers were compared with those in the screen-detected group and the non-screened population. RESULTS: Of the cancers diagnosed in the screened population, interval cancers comprised 31.2% in the first round, 47.7% in the second, and 58.9% in the third, although this was due to a decline in the numbers of screen-detected cancers rather than an increase in interval cancers. There were no consistent differences in the stage distribution of interval cancers and cancers from the non-screened population, and, in all three rounds, both overall and cancer-specific survival were significantly better for patients diagnosed with interval cancers (p<0.01). The percentage of cancers arising in women was significantly higher in the interval cancer group (50.2%) than in either the screen-detected group (35.3%, p<0.001) or the non-screened group (40.6%, p<0.001). In addition, the proportion of both right-sided and rectal cancers was significantly higher in the interval cancer group than in either the screen-detected (p<0.001) or non-screened (p<0.004) groups. CONCLUSIONS: Although GFOBT screening is associated with substantial interval cancer rates that increase with screening round, the absolute numbers do not. Interval cancers are associated with a better prognosis than cancers arising in a non-screened population, and GFOBT appears to preferentially detect cancers in men and the left side of the colon at the expense of cancers in women and in the right colon and rectum.

Experience with a wipe guaiac-based faecal occult blood test as an alternative test in a bowel screening programme.

The format of the traditional guaiac faecal occult blood test (gFOBT), particularly the collection technique, might cause difficulties for some. A multistage evaluation of alternative tests was performed. Firstly, four tests with different faecal collection approaches were assessed: a focus group recommended further investigation of a wipe gFOBT. Secondly, 100 faecal samples were analysed using two wipe tests and the routine gFOBT: no differences were found. Thirdly, a wipe gFOBT was introduced. Over 21 months, 400 requests were made and 311 wipe kit sets were submitted for analysis: 153 (49.2%) were negative, 21 (6.8%) positive (all 3 kits positive), 96 (30.9%) weak positive (1 or 2 positive) and 41 (13.2%) un-testable. Forty-three participants were referred for colonoscopy. Outcome data were provided on 39 participants: nine declined colonoscopy, two were judged unsuitable, two did not attend, two were already in follow-up, 13 had normal colonoscopy and two normal barium enema, two had diverticular disease, two had a metaplastic polyp, four had a low-risk adenoma and one had a high-risk adenoma. No participant had cancer. Detection of significant neoplasia was small. The use of the wipe gFOBT was ceased: it cannot be recommended as a screening test for bowel cancer.

Results from the first three rounds of the Scottish demonstration pilot of FOBT screening for colorectal cancer.

OBJECTIVES: To assess the effects of the first three rounds of a pilot colorectal screening programme based on guaiac faecal occult blood testing (gFOBT) and their implications for a national population-based programme. METHODS: A demonstration pilot programme was conducted in three Scottish NHS Boards. Residents aged between 50 and 69 years registered on the Community Health Index were included in the study. RESULTS: In the first round, the uptake was 55.0%, the positivity rate was 2.07% and the cancer detection rate was 2.1/1000 screened. In the second round, these were 53.0%, 1.90% and 1.2/1000, respectively, and in the third round, 55.3%, 1.16% and 0.7/1000, respectively. In the first round, the positive predictive value of the gFOBT was 12.0% for cancer and 36.5% for adenoma; these fell to 7.0% and 30.3% in the second round and were maintained at 7.5% and 29.1% in the third round. The percentage of screen-detected cancers diagnosed at Dukes' stage A was 49.2% in the first round, 40.1% in the second round and 36.3% in the third round. CONCLUSIONS: These results are compatible with those of previous randomised trials done in research settings, demonstrating that population-based colorectal cancer screening is feasible in Scotland and should lead to a comparable reduction in disease-specific mortality.

Automated immunochemical quantitation of haemoglobin in faeces collected on cards for screening for colorectal cancer.

BACKGROUND: Simple card collection systems are becoming available for faecal immunochemical tests (FITs) as well as guaiac faecal occult blood tests (gFOBTs). FITs are now obtainable that allow quantitation of haemoglobin, so that the analytical detection limit can be set to give a positivity rate that is manageable in terms of the available colonoscopy. A combination of a card collection device and an automated FIT analytical system could be advantageous. METHODS: The quantitation of haemoglobin in samples collected on cards with a new analytical system and the relationship between faecal haemoglobin concentration and pathology were investigated in a cohort of gFOBT-positive individuals. RESULTS: All groups had large ranges of haemoglobin concentration and there was overlap between the groups. Median haemoglobin concentrations in participants with normal findings on colonoscopy (167), diverticular disease (43), hyperplastic polyps (41), low risk adenoma (63), higher risk adenoma (35) and cancer (27) were 13.5, 15.6, 16.8, 15.2, 65.6 and 168.9 ng/ml haemoglobin, respectively. Those with diverticular disease, hyperplastic polyps and low risk adenoma were not significantly different from the normal group (p>0.2), but those with higher risk adenoma had significantly higher concentrations (p<0.001), as did those with cancer (p<0.001). Receiver operating characteristic analysis demonstrates that the cut-off concentration can be set to give appropriate clinical characteristics; optimum sensitivity and specificity are achieved at 26.7 ng/ml. CONCLUSIONS: The haemoglobin in faeces on simple FIT card collection devices can be immunoturbidimetrically analysed quantitatively, and the concentration relates to the presence or absence of significant neoplastic disease.

Green-coloured results on guaiac-based faecal occult blood testing should be considered positive.

BACKGROUND: In guaiac-based faecal occult blood tests (FOBT), blue colours are considered positive. Blue-green colours should also be considered positive. Distinct green colours are said to be due to bile and it is stated that these should be interpreted as negative. The purpose of this study was to determine the clinical outcomes in individuals in whom the FOBT had difficult-to-interpret green colours that did not wash out on addition of developer. METHODS: During the examination of 134 844 FOBT received in the Scottish laboratory in the first screening round of the UK Colorectal Cancer Screening Pilot, samples with green colour that did not wash out during development were identified. The clinical outcomes were determined from the comprehensive data set collected for each participant. RESULTS: A small number (77) of FOBT were recorded as green-coloured on development. These were reported as positive and the usual investigation algorithm followed. Significant pathology was present in 31 of the 77 participants (40.3%). Negative outcomes encompassed 39 of the 77 participants (50.6%). The outcome could not be determined accurately for seven of the 77 participants (9.1%). Importantly, 17 of the participants (22.1%) had polyps. CONCLUSIONS: Any green colour that does not wash out to the periphery of the guaiac tape on development of FOBT should be reported as a positive result, and manufacturers should clarify their instructions on interpretation.

The case of the floating gel.

In patients with chronic renal failure, blood samples for laboratory analysis are often taken via dialysis catheters. This report describes a case of gross spurious hypernatraemia in a blood sample collected from a patient undergoing haemodialysis. After centrifugation of the blood sample in question, the separator gel formed the topmost layer, with the serum in the middle and the clot at the bottom. Subsequent analysis of the serum showed severe hypernatraemia (serum sodium, 744 mmol/litre). It was established that the blood sample had been taken from the patient's dialysis catheter into which 3 ml of Citra-Lock (46.7% trisodium citrate) had been instilled previously as a "catheter locking" solution. The hypernatraemia seen in this case was recognised immediately as an artefact, but it was found that even minimal contamination of blood samples with Citra-Lock may significantly affect sodium concentrations. This contamination may be missed, with potentially adverse consequences for patient management.

Angiotensin converting enzyme activity in infancy is related to birth weight.

AIMS: (a) To measure infant angiotensin converting enzyme (ACE) activity in healthy term infants at birth and during the first three months of life. (b) To determine the relation between serum ACE activity and infant feeding practice during this period. (c) To investigate the relation between serum ACE activity and birth weight and other potential contributing factors including acid-base status at birth, gestation, and maternal ACE genotype. METHODS: Prospective study of term infants, with clinical and feeding data collected from parents and medical records, and serum ACE measured in the infant at birth and 1 and 3 months of age, and in the mother at the time of birth and one to three months after birth. RESULTS: At birth and 1 and 3 months of age, infant serum ACE activity was twice that of maternal ACE activity. Infant ACE activity at birth and 1 and 3 months did not significantly differ between breast and formula fed infants. There was a highly significant negative correlation between infant ACE activity at 3 months and birth weight (r = -0.52; p < 0.001). This persisted after the conversion of birth weights to z scores (r = -0.34; p = 0.03). ACE activity at 3 months was also related to placental weight (r = -0.30; p = 0.02) and maternal age (r = -0.30; p = 0.05). The strong correlation between serum ACE activity and birth weight z score persisted after adjustment for maternal age and placental weight (r = -0.34; p = 0.03). CONCLUSION: As ACE is increasingly identified as a risk factor for cardiovascular disease, serum ACE activity in infancy may contribute to the link between low birth weight and later cardiovascular events.

Influence of index of individuality on false positives in repeated sampling from healthy individuals.

The index of individuality is defined as the ratio of the within-subject biological variation to the between-subject variation, i.e., the variation between the biological set-points. It has been disputed whether the index of individuality has influence on the usefulness of conventional population-based reference intervals. In this investigation we found that, as long as only a single sample is taken, for a certain change in an individual's set-point, the index of individuality has no influence on the usefulness of reference intervals. When two or more samples are taken into account, however, the outcome of the measurement is highly dependent on the index of individuality. For a low index, repeat measurement has only limited effect on the fraction of false-positive results, as the next result will be close to the first, but, when the index is high, the fraction of false-positive results will be reduced considerably through repeating the test. Moreover, the distribution of biological set-points for which the fraction of false-positive results originate is described and the influence of analytical imprecision is discussed. The calculations are performed for values of the index of individuality from 0 to 2.0 for the traditional 95% reference interval based on x +/- 2*s(total) (s(total) = total biological variation), and also for a decision limit (cut-off point) x +/- 3*s(total). The numbers are, of course, different, but the effects of the index of individuality are the same, independent of the chosen cut-off point. This concept is related to the clinical classification (diagnosis, prognosis, screening) and the difference from different principles of monitoring is discussed. Further, five examples are evaluated and aspects of index of individuality in relation to false-positive results are discussed.

Optimal analytical performance for point of care testing.

Quality specifications for the reliability of performance characteristics of laboratory testing, particularly precision and bias, are necessary prerequisites for creation and control of analytical quality. Many strategies have been promulgated for setting these specifications. Recently, the available approaches have been fixed into a hierarchical framework that has now been accepted by experts in the field to be the best current approach to a global strategy for setting quality specifications in laboratory medicine. They should be incorporated into quality planning strategies everywhere irrespective of the settings in which laboratory medicine is practised, including the point of care testing (POCT). Models higher in the hierarchy are preferred to lower approaches but lower approaches are better than none and should be used as the minimum standard.

A model for setting analytical quality specifications and design of control for measurements on the ordinal scale.

A model for characterization of measurements on the ordinal scale is presented. It is based on transformation of the calculated fractions (fractiles) of positives from measurements on samples with known concentrations to a probit-natural log (probit-ln) scale. Such measurements could be made by other methods on ratio or difference scales but, for convenience (for example for speed or low cost), are measured on the ordinal scale by "simple" methods. The model is examined, and verified, using three examples from published data (haemoglobin, glucose, and leukocytes) and an external quality assessment survey on measurements of streptococcus. We show that it is possible to obtain reliable analytical quality specifications and to establish design of control systems for measurements on the ordinal scale. It is concluded that the presented probit-ln model for the ordinal scale is a tool which can improve and facilitate (i) characterizing methods with measurements on the ordinal scale, (ii) defining analytical quality specifications, (iii) designing external assessment as well as internal control schemes, (iv) validation of methods with measurements on the ordinal scale according to the analytical quality specifications, and further, (v) reduction of the number of samples required for method validation and the number of replicate measurements needed.

The index of individuality is often a misinterpreted quantity characteristic.

The concept of the "index of individuality" was introduced by Eugene Harris in 1974. The index of individuality, calculated as (CV(A)2 + CV(I)2)(1/2)/CV(G), where CV(A), CV(I), and CV(G) are analytical, within-subject, and between-subject coefficients of variation respectively, has been used by many to investigate the utility of conventional population-based reference values. For a high index of individuality, > 1.4, it has been said that reference intervals will be more useful than for a low index, < 0.6. The validity of these concepts is investigated here and a number of our findings are at odds with the generally held opinion. The index of individuality has no impact on the fraction of individuals classified using population-based reference values, as long as the change in concentration from the usual state is of the same absolute magnitude and one sample is assayed to detect disease. However, when a measurement falling outside a reference limit is repeated in order to verify the finding, the index of individuality has considerable influence. For quantities with very low indices, the repeat test result, will be close to the first and give no new information, whereas for quantities with high indices, a repeat test will decrease the number of true positives and false positives.