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.

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.

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.

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.

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.

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.

Desirable standards for hematology tests: a proposal.

Few analytic goals have been proposed for hematology tests, and these are based upon subjective clinical opinions. It is proposed that the current consensus strategies for delineating analytic goals in clinical chemistry can be validly used in the other disciplines of clinical pathology. Goals for imprecision are best based upon average intraindividual biologic variation; such goals are more stringent than those previously published. There are many cogent reasons that justify the goal for inaccuracy of no bias. In consequence, goals for imprecision should be viewed as goals for total laboratory error. Further experimental work on biologic variation is required to develop a wider range of goals for hematology and coagulation tests, if these strategies are considered worthy of adoption.

Biologic variation of common hematologic laboratory quantities in the elderly.

Analytic, within-subject, and between-subject biologic variations were estimated for leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin content (MCHC), platelets, and a three-component differential count (lymphocytes, monocytes, and granulocytes in terms of both concentration and percentage of leukocytes) in cohorts of 12 male and 12 female healthy elderly subjects. The assays were performed with an Ortho ELT-800 automated analyzer. The estimates of within-subject biologic variation were similar to published data on young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. The data were used to derive objective analytic goals; goals were surpassed except for assays of erythrocytes, hematocrit, and the derived MCV, MCH, and MCHC. The changes required for serial results to be significantly different were determined and found to be generally valid because most quantities have no heterogeneity of within-subject variation. All quantities had significant individuality; in consequence, conventional population-based reference values are of limited utility, and screening using reference limits will not detect latent or early disease in many subjects.

Evolution of a national urine quality assurance programme: the Australasian experience, 1981-1983.

A national interlaboratory quality assurance programme for quantitative urine analysis has been conducted over the past three years in Australasia under the auspices of the Royal College of Pathologists of Australasia and the Australian Association of Clinical Biochemists. Analysis of urine calcium has consistently improved over the three year period whereas urine protein analysis has consistently declined. Based on the findings in 1983, it is considered that urine sodium, potassium, creatinine, phosphate, glucose, and chloride are currently being measured satisfactorily by Australasian laboratories, while the analyses of urine proteins, urate, oxalate, 5-hydroxyindoleacetic acid and 4-hydroxy-3-methoxymandelic acid still require substantial improvement.

A clinical view of analytical goals in clinical biochemistry.

The analytical goals inferred desirable by a group of clinicians for the imprecisions of a wide range of analytes have been studied by survey. The goals required have not in general become more stringent in the past decade and are not as demanding as those promulgated by laboratory professionals. Clinical biochemistry laboratories can now attain analytical imprecisions which satisfy the general demands of clinicians except for analyses of calcium and of low levels of glucose. The lack of published data on analytical goals does not allow wide comparison of criteria for performance standards with the results of this study.

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.

Assessment of the Beckman creatinine analyzer 2.

An evaluation of the Beckman Creatinine Analyzer 2 has been carried out. Good day-to-day and within-day precision was obtained. Analyses of quality control materials, studies of linearity, and comparison of the results obtained for samples from patients with the results obtained by a continuous-flow method evidenced good accuracy. Aceto-acetate in serum caused significant positive interference. The desirable performance characteristics and practicability make this Analyzer attractive to the clinical chemist, particularly for paediatric and emergency laboratory use.

Assessment of colorimetric enzymatic determination of triglyceride, by manual and centrifugal analyzer techniques, and comparison with a CDC standardized method.

We describe the assessment of an enzymatic method, with colorimetric detection, for the determination of triglyceride. Two commercial single vial reagent sets were evaluated, by manual and centrifugal analyzer techniques, and compared to a method which had attained standardized status from the Center for Disease Control (CDC). Precision and accuracy obtained on analysis of CDC reference materials, and precision obtained on analysis of plasma samples, did not fulfill the criteria of CDC. The precision met the criteria of the College of American Pathologists based upon intra-individual variation. Good correlation between the reagent set method and a continuous-flow method with prior extraction was evident but proportional and constant biases were found. The method would be suitable for routine use particularly if a centrifugal analyzer was employed. If a manual method was used it is recommended that blanks be performed on samples. The method had acceptable linearity. Use of a constant relationship between concentration and absorbance did not lead to improved performance characteristics.

Comparison of standardization techniques for manual colorimetric analyses.

The influence of both the mode of standardization and the type of standard on the precision of four manual colorimetric methods performed under optimal conditions variance is described. The terms variable calibration mode and constant calibration mode are proposed; these describe standardization by within-run standards and standardization by a predetermined calibration relationship between concentration and absorbance that remains constant over a fixed period of time. We show that calibration relationships and mode of standardization must be established for each and every individual method on objective evidence. Where within-run standards are used, they must be carefully selected for each method. The implications for method evaluation and quality control are discussed.

Assessment of the Beckman oxygen rate analyzer for the enzymatic assay of cholesterol.

We describe an evaluation of the Beckman oxygen rate analyzer for the determination of cholesterol. The precision and accuracy obtained did not fulfill the short-term criteria of the Center for Disease Control but the precision met the criteria of the College of American Pathologist for analysis of cholesterol in screening programs. Good overall correlation between the oxygen rate method and a continuous-flow method with prior extraction was found for patient samples. The results obtained by the oxygen rate method had net positive bias up to the limit of linearity of 8.6 mmol cholesterol/liter. The instrument is not recommended for laboratory or epidemiological studies but may prove useful in screening programs.

Comparison of standardization techniques for colorimetric analyses on a centrifugal analyzer.

The influences of the mode of standardization and the type of standard on the precision of four mechanized methods performed on a centrifugal analyzer are described. Experimental results show that the mode of standardization -- variable, using a standard in each analytical batch, and constant, using a direct relationship between concentration and absorbance -- must be objectively selected. If the variable mode is chosen, the type and level of standard must be carefully chosen and absorbance of assays of the standard must be carefully monitored for good quality control. It is recommended that the optimum standardization technique and standard, where applicable, should be assessed and subsequently documented in evaluations of methods, kits and instruments.

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.