The impact of primary-care led, faecal immunochemical test-based, triage of new-onset colorectal symptoms on time to diagnosis of colorectal cancer-An observational study.

AIM: Since December 2015, a faecal immunochemical test (FIT) has been provided to primary care in NHS Tayside as an adjunct to clinical acumen in the assessment of new-onset bowel symptoms. The aim of this work was to assess the impact of this approach on time to diagnosis of colorectal cancer (CRC). METHOD: NHS Tayside Cancer audit data from January 2013 to December 2019 were reviewed to identify all CRC patients diagnosed via the primary-care referral pathway for a period before and after the introduction of FIT. Their electronic patient records were accessed and date of referral and any contemporaneous FIT and full blood count (FBC) result were recorded. Time from referral to diagnosis of CRC was calculated for each patient and compared between subgroups. RESULTS: The study cohort consisted of 959 patients: 378 and 581 from the time periods before and after the introduction of FIT, respectively. The median time to diagnosis before FIT was 30 days [interquartile range (IQR) 16-57 days] versus 25 days (IQR 14-47 days) following the introduction of FIT (p = 0.006). Following the introduction of FIT, patients who completed a FIT had a median of time to diagnosis of 23 days (IQR 14-43 days) compared with 30 days (IQR 16-62 days) for patients not completing a FIT (p = 0.019). FBC results were available for 97.5% of FIT patients to aid safety-netting of patients with a low or undetectable faecal haemoglobin concentration. CONCLUSION: The introduction of FIT-based triage of new bowel symptoms in primary care as an adjunct to clinical acumen is associated with a reduced time to CRC diagnosis.

Impact of faecal haemoglobin based triage of bowel symptoms presenting to primary care on colorectal cancer diagnosis.

AIM: Faecal immunochemical testing (FIT) for faecal haemoglobin was introduced into primary care in National Health Service Tayside in 2015 as an adjunct to clinical assessment of new bowel symptoms. We aimed to assess the impact of FIT-based triage in primary care on colorectal cancer (CRC) diagnosis. METHOD: Cancer audit data between January 2016 and December 2019 were reviewed to identify all patients diagnosed locally with CRC. The mode of presentation and stage at diagnosis were noted and patient records were interrogated to identify whether FIT and full blood count (FBC) had been performed prior to referral. Results were compared between the FIT and non-FIT groups. RESULTS: In all, 1245 patients were diagnosed with CRC of whom 581 (46.7%) presented through primary care. FIT was performed prior to referral in 440/581 (75.7%), with the proportion increasing from 62.3% in 2016 to 85.8% in 2019. At faecal haemoglobin ≥10 µg Hb/g faeces, sensitivity for CRC was 94.1%. Over the study period the annual proportion of non-emergency presentations increased significantly; presentations from primary care increased from 43.1% to 53.5% (P = 0.0096). After excluding non-FIT patients who had an overt CRC at referral, there was no difference in stage at diagnosis between FIT and non-FIT cancers. Safety-netting with FBC was widely used in our cohort with 97.3% of FIT patients having also had FBC. CONCLUSION: FIT-based triage of new bowel symptoms in primary care is associated with increased non-emergency presentation of CRC but this did not influence stage at diagnosis.

Age-adjusted D-dimer excludes pulmonary embolism and reduces unnecessary radiation exposure in older adults: retrospective study.

BACKGROUND: Patients in whom a diagnosis of pulmonary embolism (PE) is suspected and whose D-dimers are elevated frequently require CT pulmonary angiogram (CTPA) for diagnosis. Because D-dimer rises with age, an age-adjusted D-dimer threshold may prevent unnecessary radiation exposure from CTPA in older patients. OBJECTIVE: To determine the efficacy and safety of implementing an age-adjusted D-dimer threshold to exclude PE. DESIGN, SETTINGS AND PATIENTS: Retrospective comparison of conventional and age-adjusted D-dimer thresholds in 1000 consecutive patients who had both D-dimer and CTPA. MAIN OUTCOME MEASURES: Conventional and age-adjusted D-dimer thresholds for excluding PE were <250 ng/mL and 5× age for patients older than 50 years, respectively. We defined patients as unlikely to have PE using the revised Geneva score (RGS) and two different categories of clinical risk: RGS ≤5 and RGS ≤10. RESULTS: We diagnosed PE by CTPA in 244 (24.4%) patients. 3/86 patients (3.5%) whose D-dimer was below the conventional threshold of 250 ng/mL had PE (RGS 3, 9 and 14), all of which were judged to be light clot load (group 1). 3/108 patients (2.8%) whose D-dimer lay between 250 ng/mL and the age-adjusted threshold had PE (RGS 6, 8 and 9), all of which were again judged to be light clot load (group 2). 62/108 group 2 patients with RGS ≤5 were considered unlikely to have PE as were 102/108 using the RGS clinical risk category ≤10. None of the 62 patients with RGS ≤5 had PE while 3/102 patients with RGS ≤10 had PE. 236/806 patients (29.3%) whose D-dimer was above the age-adjusted threshold had PE (group 3). CONCLUSIONS: In a consecutive series of 1000 patients, an RGS ≤5 and an age-adjusted D-dimer would have led to 62 fewer CTPA at a cost of no missed PEs.

Emergency presentation of colorectal cancer in older adults: A retrospective cohort analysis.

INTRODUCTION: Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (<70 years) adults in our population. MATERIALS AND METHODS: The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (<70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses. RESULTS: In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20-98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p < 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p < 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p < 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p < 0.001). Whilst older adults had poorer median OS than those aged <70 years (12.0 vs 34.4 months, p < 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.7, stage IV HR 16.7, 95% CI 9.7-28.8, incomplete HR 8.2, 95% CI 4.6-14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7-4.0) were associated with poorer survival, whereas age and sex were not. DISCUSSION: Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.

Intelligent Liver Function Testing (iLFT): An Intelligent Laboratory Approach to Identifying Chronic Liver Disease.

The intelligent Liver Function Testing (iLFT) pathway is a novel, algorithm-based system which provides automated laboratory investigations and clinical feedback on abnormal liver function test (LFT) results from primary care. iLFT was introduced to NHS Tayside, Scotland, in August 2018 in response to vast numbers of abnormal LFTs, many of which were not appropriately investigated, coupled with rising mortality from chronic liver disease. Here, we outline the development and implementation of the iLFT pathway, considering the implications for the diagnostic laboratories, primary care services and specialist hepatology clinics. Additionally, we describe the utility, outcomes and evolution of iLFT, which was used over 11,000 times in its first three years alone. Finally, we will consider the future of iLFT and propose areas where similar 'intelligent' approaches could be used to add value to laboratory investigations.

Enhanced liver fibrosis (ELF) score predicts hepatic decompensation and mortality.

Background & Aims: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway. Methods: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited. Case note review was undertaken to compare ELF with endpoints of cirrhosis, hepatic decompensation, and mortality (liver-related and all-cause death). Results: In total, 1,327 individuals were included with a median follow-up of 859 days and median ELF score of 10.2. Overall sensitivity for cirrhosis at the 9.8 threshold was 94% (100% for metabolic-associated steatotic liver disease, 89% for alcohol-related liver disease). Determination of the ELF score as a second-line test reduced the referral rate by 34%. ELF scores predicted hepatic outcomes; each unit change was associated with increased decompensation (adjusted Hazard Ratio [aHR] 2.215, 95% CI: 1.934-2.537) and liver-related mortality (aHR 2.024, 95% CI: 1.674-2.446). ELF outperformed FIB-4 for risk of liver-related mortality, particularly in the short-term (area under the curve [AUC] 94.3% vs. 82.8% at six months). Where FIB-4 was indeterminate, ELF had higher AUC for all outcomes within at least 2 years. ELF ≥13 was associated with particularly high rates of decompensation (26% within 90 days) and all-cause mortality (38% at 1 year). Conclusions: The addition of ELF reduced the number of individuals referred for fibrosis assessment following iLFT pathway testing and provided useful prognostic information. Individuals with ELF scores ≥13 were considered at high-risk of negative outcomes warranting urgent clinical assessment. Impact and implications: Primary care pathways for suspected liver disease are increasingly common and often lead to increased specialist hepatology referrals for fibrosis assessment. This study, using clinical follow-up for liver-related outcomes, provides further evidence supporting ELF testing to safely reduce referrals in a two-step approach when combined with other simple fibrosis markers. Additionally, ELF scores predict liver-related morbidity and mortality, with ELF scores ≥13 indicating particularly high-risk patients. This study may help inform the implementation of diagnostic pathways for early detection of liver disease and highlights the need for urgent review of individuals with very high ELF scores.

Thrombocytosis and abnormal liver enzymes: A trigger for investigation of underlying malignancy.

BACKGROUND: Thrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer. METHODS AND FINDINGS: Between August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7-11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0-3.7%) of controls. Patients <40 years or with pre-existing causes of thrombocytosis were then excluded. Subsequent analysis revealed a 10.8% (6.6-16.3%) incidence of cancer in thrombocytosis patients (n = 176) compared to 2.5% (1.2-4.6%, p = 0.00014) in patients with normal platelet count (PLT) (n = 398). When thrombocytosis is combined with elevated alkaline phosphatase (ALP), there is a positive predictive value (PPV) of 20% for cancer. These rules were subsequently applied to a validation cohort of 71,652 patients, of whom 458 had thrombocytosis and elevated ALP. There was a 30.6% cancer incidence, confirming the strong predictive value of the combined test of PLT and ALP. CONCLUSIONS: These findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated.

Intelligent Liver Function Testing: Working Smarter to Improve Patient Outcomes in Liver Disease.

Chronic liver disease (CLD) is a significant health problem affecting millions of people worldwide. In Scotland, CLD is a major cause of premature mortality. Liver function tests (LFTs) are a panel of frequently requested blood tests which may indicate liver disease. However, LFTs commonly contain at least one abnormal result, and abnormalities are rarely investigated to the extent recommended by national guidelines. The intelligent Liver Function Testing (iLFT) pathway is a novel, automated system designed to improve early diagnosis of liver disease. Initial abnormal LFT results trigger a cascade of reflexive testing to help identify the cause of any liver dysfunction. Algorithms combine these results with demographic and clinical data (such as patient age, body mass index, and alcohol intake) and fibrosis estimates to produce an electronic diagnosis and management plan. The pilot trial demonstrated that iLFT increased diagnosis of liver disease whilst remaining cost-effective. As such, iLFT has been fully operational across our region (NHS Tayside, Scotland) since August 2018. In the first year, iLFT generated over 2000 diagnoses from 1824 patient samples with an abnormality in the initial LFTs. The majority of these patients could be safely managed in primary care. iLFT allows maximal value to be obtained from liver blood tests across biochemistry, virology, immunology, and hematology with only minor changes to working practices. 'Intelligent', algorithm-led testing pathways break down the barrier between clinical and laboratory medicine and offer solutions to many of the challenges experienced in modern healthcare systems.