Root-cause analyses of missed opportunities for the diagnosis of colorectal cancer in patients with inflammatory bowel disease

Background: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice. Aim: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cause analyses to identify patients with missed opportunities to diagnose IBD-associated CRC. We matched patients with IBD-associated CRC to patients with CRC in the general population to identify differences in staging at diagnosis and clinical outcomes. Results: Compared with the general population, patients with IBD were at increased risk of developing CRC (odds ratio 2.7 [95% CI 1.6-3.9], P < 0.001). The mean incidence of IBD-associated CRC between 1998 and 2019 was 165.4 (IQR 130.4-199.4) per 100 000 patients and has not changed over the last 20 years. Seventy-eight patients had IBD-associated CRC. Forty-two (54%) patients were eligible for CRC surveillance: 12% (5/42) and 10% (4/42) patients were diagnosed with CRC at an appropriately timed or overdue surveillance colonoscopy, respectively. Interval cancers occurred in 14% (6/42) of patients; 64% (27/42) of patients had a missed opportunity for colonoscopic surveillance where root-cause analyses demonstrated that 10/27 (37%) patients known to secondary care had not been offered surveillance. Four (15%) patients had a delayed diagnosis of CRC due to failure to account for previous colonoscopic findings. Seventeen (63%) patients were managed by primary care including seven patients discharged from secondary care without a surveillance plan. Matched case-control analysis did not show significant differences in cancer staging or 10-year survival outcomes. Conclusion: The incidence of IBD-associated CRC has remained static. Two-thirds of patients eligible for colonoscopic surveillance had missed opportunities to diagnose CRC. Surveillance programmes without comprehensive and fully integrated recall systems across primary and secondary care are set to fail.published version, accepted version (12 month embargo), submitted versionThis article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site

Root-cause analyses of missed opportunities for the diagnosis of colorectal cancer in patients with inflammatory bowel disease

Background: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice. Aim: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cause analyses to identify patients with missed opportunities to diagnose IBD-associated CRC. We matched patients with IBD-associated CRC to patients with CRC in the general population to identify differences in staging at diagnosis and clinical outcomes. Results: Compared with the general population, patients with IBD were at increased risk of developing CRC (odds ratio 2.7 [95% CI 1.6-3.9], P < 0.001). The mean incidence of IBD-associated CRC between 1998 and 2019 was 165.4 (IQR 130.4-199.4) per 100 000 patients and has not changed over the last 20 years. Seventy-eight patients had IBD-associated CRC. Forty-two (54%) patients were eligible for CRC surveillance: 12% (5/42) and 10% (4/42) patients were diagnosed with CRC at an appropriately timed or overdue surveillance colonoscopy, respectively. Interval cancers occurred in 14% (6/42) of patients; 64% (27/42) of patients had a missed opportunity for colonoscopic surveillance where root-cause analyses demonstrated that 10/27 (37%) patients known to secondary care had not been offered surveillance. Four (15%) patients had a delayed diagnosis of CRC due to failure to account for previous colonoscopic findings. Seventeen (63%) patients were managed by primary care including seven patients discharged from secondary care without a surveillance plan. Matched case-control analysis did not show significant differences in cancer staging or 10-year survival outcomes. Conclusion: The incidence of IBD-associated CRC has remained static. Two-thirds of patients eligible for colonoscopic surveillance had missed opportunities to diagnose CRC. Surveillance programmes without comprehensive and fully integrated recall systems across primary and secondary care are set to fail.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo), submitted versio

O11 Outcomes of GP outreach programme offering colonoscopic surveillance for IBD patients managed in primary care

Introduction Colonoscopic surveillance in IBD patients can reduce the development of colorectal cancer (CRC) and the rate of CRC-associated death. We recently reported that 27% of IBD patients living in East Devon are managed exclusively in primary care of whom about 23% maybe eligible for colonoscopic surveillance. We devised an outreach programme, whereby we invited primary care physicians to enrol these patients in a colonoscopic surveillance programme.Methods In December 2017 we contacted 37 general practices, where 161 patients with UC who were eligible for surveillance had been identified. Each practice was sent a letter explaining the goals of the project, a link to the National Institute for Healthcare and Clinical Excellence (NICE) guidance for CRC surveillance in IBD patients and patient information booklets. We informed the practices of their eligible patients and asked them to refer patients for secondary care IBD consults if appropriate. We included an outcome form that captured whether the patient was referred, was deemed inappropriate for surveillance, had surveillance elsewhere, had declined surveillance, or was no longer registered at the practice.Results Sixty-five percent of practices (24/37) responded and we received responses for 57 of 161 (35%) potentially eligible patients. Thirty-five (61%) patients were referred to our IBD service; 7 (12%) patients declined surveillance; 7 (12%) patients were deemed by their GP to be unfit for surveillance and 5 (10%) were no longer registered at the identified GP practice; 2 (4%) had surveillance arranged elsewhere and 1 (2%) patient had died. Amongst the 35 patients referred to secondary care; 22 (63%) underwent surveillance colonoscopy, 12 (34%) declined surveillance after discussion or did not attend their booked appointments and one is awaiting colonoscopy. Half of patients who had a colonoscopy had active inflammation. We diagnosed one CRC He was an elderly man with a locally invasive signet ring caecal tumour, without distant metastases, who went onto to have a curative right hemicolectomy without complication.Conclusions Patients with longstanding IBD are frequently managed exclusively in primary care and maybe overlooked for colonoscopic CRC surveillance. There is a need to implement processes to facilitate identification and recall of patients eligible for surveillance across primary and secondary care.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted version, submitted versio

Factors associated with depression in people with inflammatory bowel disease: The relationship between active disease and biases in neurocognitive processing

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Background Depression is common among people with inflammatory bowel disease (IBD), though the causes remain unclear. We conducted a cross-sectional study to investigate the role of emotional processing biases in contributing to depression among people with IBD. Materials and methods One hundred and twenty outpatients with IBD were recruited and: i) completed questionnaires to record: age, sex, social support, socioeconomic status, anxiety and depression (n=104) , ii) underwent assessments of biases in emotional recognition (n=112), emotional memory and reinforcement learning iii) had recorded from clinical records: type of IBD, duration of IBD, IBD activity and iv) provided blood for high-sensitivity C-reactive protein levels (n=99). Key Results Sixty-eight participants had Crohn’s disease and 49 had ulcerative colitis. Of these, 35 had active disease and 26 had depression. Those with depression were more likely to be female, lack social support, have active disease, be taking corticosteroids but not TNF-alpha inhibitors and exhibit less positive emotional recognition bias. On multivariable regression analysis, depression was associated independently with lack of social support (unstandardized regression coefficient (B)=-1.40, p=0.02) and increased disease activity (B=1.29, p=0.03). Causal steps analysis was consistent with less positive emotional recognition bias partially mediating the effects of disease activity on depression. Conclusions and inferences This is the first study to demonstrate links between disease activity and less positive biases in emotional recognition that could explain higher rates of depression among people with active IBD. Future prospective studies are required to confirm the effects of emotional processing biases in depression and allow stronger causal inferences to be drawn.University of Exete

Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report

Background: Juvenile hemochromatosis is the most severe form of iron overloading phenotype. Although rare, it should be suspected in patients who present with hypogonadotropic hypogonadism, diabetes mellitus, or cardiomyopathy without a clear cause. Case presentation: A young Serbian male presenting with end-stage heart failure was referred for extracorporeal membrane oxygenation. An endomyocardial biopsy revealed cytoplasmic iron deposits in myocytes. His condition was stabilized with biventricular assist devices and he was listed for heart transplantation. Iron chelation therapy was commenced and resulted in rapid removal of iron burden. Serial outpatient echocardiograms demonstrated myocardial recovery such that a successful biventricular assist device explant occurred 131 days after initial implant. Targeted gene sequencing revealed a loss-of-function mutation within the HJV gene, which is consistent with juvenile hemochromatosis. Conclusions: This rare case of a patient with juvenile hemochromatosis associated with a HJV mutation provides histologic evidence documenting the reversal of associated end-stage heart failure, requiring emergent mechanical circulatory support, with iron chelation therapy

Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study

Objective: To determine the diagnostic accuracy of calprotectin to diagnose inflammatory bowel disease (IBD) in children in whom general practitioners (GPs) suspected IBD. Design: Prospective observational cohort study of a new calprotectin-based primary care referral pathway. Setting: 48 GP practices and gastroenterology secondary care services at the Royal Devon and Exeter NHS Foundation Trust in the South-West of England, UK. Patients: 195 children aged between 4 and 18 years referred on the pathway between January 2014 and August 2017 for investigation of gastrointestinal symptoms were included. Interventions: Primary-care-driven faecal calprotectin testing. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. Main outcome measures: Diagnostic accuracy of calprotectin testing to detect IBD. Results: 7% (13/195) tested patients were diagnosed with IBD. Using our prespecified cut-off of 100 µg/g, calprotectin had a diagnostic accuracy of 91% (95% CI 86% to 95%) with a sensitivity for distinguishing IBD from non-IBD of 100% (95% CI 75% to 100%), a specificity of 91% (95% CI 85% to 94%), a positive predictive value of 43% (95% CI 25% to 63%) and a negative predictive value of 100% (95% CI 98% to 100%). Calprotectin testing had no effect on the time to diagnosis, but a negative test contributed to saved referrals and was associated with fewer diagnostic tests in secondary care. Conclusions: Calprotectin testing of children with suspected IBD in primary care accurately distinguishes IBD from a functional gut disorder, reduces secondary care referrals and associated diagnostic healthcare utilisation.This article is available to RD&E staff via NHS OpenAthens. Click on the Publisher URL, and log in with NHS OpenAthens if prompted.published version, accepted version, submitted versio

Clinical features and genetic risk of demyelination following anti-TNF treatment

Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and test whether affected patients were genetically predisposed to multiple sclerosis (MS). Methods: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF. We compared genetic risk scores (GRS), calculated using carriage of 43 susceptibility loci for MS, in 48 cases to 1219 patients exposed to anti-TNF who did not develop demyelination. Results: Overall, 39 (74%) cases were female. The median age (range) of patients at time of demyelination was 41.5 years (20.7 - 63.2). The median duration of anti-TNF treatment was 21.3 months (0.5 - 99.4) and 19 (36%) patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord or both. Complete recovery was reported in 12 (23%) patients after a median time of 6.8 months (0.1 - 28.7). After 33.0 months of follow-up partial recovery was observed in 29 (55%) patients, relapsing and remitting episodes in 9 (17%), progressive symptoms in 3 (6%): 2 (4%) patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 x 10-4, SD 0.0039) and controls (mean -1.1×10-3, SD 0.0042) (p=0.23). Conclusions: Patients who experienced demyelination events following anti-TNF were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.published version, accepted version (12 month embargo), submitted versio