The Time to Inflammatory Bowel Disease Diagnosis for Patients Presenting with Abdominal Symptoms in Primary Care and its Association with Emergency Hospital Admissions and Surgery: A Retrospective Cohort Study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes. METHODS: A retrospective cohort study using English primary care data from January 1, 2010, to December 31, 2019, linked to hospital admission data was undertaken. Patients were followed from the first IBD-related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models, respectively. RESULTS: Of 28 092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn's disease (CD). The median age was 43 (interquartile range, 30-58) years and 51.9% were female. Median time to diagnosis was 15.6 (interquartile range, 4.3-28.1) months. Factors associated with more than a year to diagnosis included female sex (adjusted risk ratio [aRR], 1.23; 95% CI, 1.21-1.26), older age (aRR, 1.05; 95% CI, 1.01-1.10; comparing >70 years of age with 18-30 years of age), obesity (aRR, 1.03; 95% CI, 1.00-1.06), smoking (aRR, 1.05; 95% CI, 1.02-1.08), CD compared with UC (aRR, 1.13; 95% CI, 1.11-1.16), and a fecal calprotectin over 500 µg/g (aRR, 0.89; 95% CI, 0.82-0.95). The highest quartile of time to diagnosis compared with the lowest was associated with IBD-related emergency admissions (incidence rate ratio, 1.06; 95% CI, 1.01-1.11). CONCLUSION: Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn's disease. More IBD-related emergency admissions were observed in patients with a prolonged time to diagnosis.

On average, patients with inflammatory bowel disease experience a 16-month diagnostic delay from symptom onset in primary care. Fecal calprotectin testing expedited diagnosis. Longer diagnostic periods were associated with an increased risk of emergency hospital admissions but not with inflammatory bowel disease­related surgery.

Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus.

BACKGROUND: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). METHODS: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. RESULTS: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. CONCLUSION: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.

Umbrella systematic review of potential quality indicators for the detection of dysplasia and cancer at upper gastrointestinal endoscopy.

Background and study aims Upper gastrointestinal (UGI) endoscopy lacks established quality indicators. We conducted an umbrella systematic review of potential quality indicators for the detection of UGI cancer and dysplasia. Methods Bibliographic databases were searched up to December 2021 for systematic reviews and primary studies. Studies reporting diagnostic accuracy, detection rates or the association of endoscopy or endoscopist-related factors with UGI cancer or dysplasia detection were included. AMSTAR2 and JBI checklists were used to assess systematic review and primary study quality. Clinical heterogeneity precluded meta-analysis and findings are summarized narratively. Results Eight systematic reviews and nine primary studies were included. Image enhancement, especially narrow band imaging, had high diagnostic accuracy for dysplasia and early gastric cancer (pooled sensitivity 0.87 (95% CI 0.84-0.89) and specificity 0.97 (0.97-0.98)). Higher detection rates with longer endoscopy examination times were reported in three studies, but no difference was observed in one study. Endoscopist biopsy rate was associated with increased gastric cancer detection (odds ratio 2.5; 95% confidence interval [CI] 2.1-2.9). Early esophageal cancer (0.17% vs 0.14%, P =0.04) and gastric cancer (0.16% vs 0.12%, P =0.02) detection rates were higher with propofol sedation compared to no sedation. Endoscopies performed by trained endoscopists on dedicated Barrett's surveillance lists had higher detection rates (8% vs 3%, P <0.001). The neoplasia detection rate during diagnostic endoscopies for Barrett's esophagus was 7% (95% CI 4%-10%). Conclusions Image enhancement use, longer examination times, biopsy rate and propofol sedation are potential quality indicators for UGI endoscopy. Neoplasia detection rate and dedicated endoscopy lists are additional potential quality indicators for Barrett's esophagus.

A root cause analysis system to establish the most plausible explanation for post-endoscopy upper gastrointestinal cancer.

BACKGROUND : Missing upper gastrointestinal cancer (UGIC) at endoscopy may prevent curative treatment. We have developed a root cause analysis system for potentially missed UGICs at endoscopy (post-endoscopy UGIC [PEUGIC]) to establish the most plausible explanations. METHODS : The electronic records of patients with UGIC at two National Health Service providers were examined. PEUGICs were defined as UGICs diagnosed 6-36 months after an endoscopy that did not diagnose cancer. An algorithm based on the World Endoscopy Organization post-colonoscopy colorectal cancer algorithm was developed to categorize and identify potentially avoidable PEUGICs. RESULTS : Of 1327 UGICs studied, 89 (6.7 %) were PEUGICs (patient median [IQR] age at endoscopy 73.5 (63.5-81.0); 60.7 % men). Of the PEUGICs, 40 % were diagnosed in patients with Barrett's esophagus. PEUGICs were categorized as: A - lesion detected, adequate assessment and decision-making, but PEUGIC occurred (16.9 %); B - lesion detected, inadequate assessment or decision-making (34.8 %); C - possible missed lesion, endoscopy and decision-making adequate (8.9 %); D - possible missed lesion, endoscopy or decision-making inadequate (33.7 %); E - deviated from management pathway but appropriate (5.6 %); F - deviated inappropriately from management pathway (3.4 %). The majority of PEUGICs (71 %) were potentially avoidable and in 45 % the cancer outcome could have been different if it had been diagnosed on the initial endoscopy. There was a negative correlation between endoscopists' mean annual number of endoscopies and the technically attributable PEUGIC rate (correlation coefficient -0.57; P = 0.004). CONCLUSION : Missed opportunities to avoid PEUGIC were identified in 71 % of cases. Root cause analysis can standardize future investigation of PEUGIC and guide quality improvement efforts.

The association between inflammatory bowel disease and mental ill health: a retrospective cohort study using data from UK primary care.

BACKGROUND: Patients with active inflammatory bowel disease (IBD) and mental illnesses experience worse IBD outcomes. AIM: To describe the incidence of mental illnesses, including deliberate self-harm, in IBD patients. METHODS: A population-based retrospective cohort study using IQVIA medical research data of a primary care database covering the whole UK, between January 1995 and January 2021. IBD patients of all ages were matched 4:1 by demographics and primary care practice to unexposed controls. Following exclusion of patients with mental ill health at study entry, adjusted hazard ratios (HR) of developing depression, anxiety, deliberate self-harm, severe mental illness and insomnia were calculated using a Cox proportional hazards model. RESULTS: We included 48,799 incident IBD patients: 28,352 with ulcerative colitis and 20,447 with Crohn's disease. Incidence rate ratios of mental illness were higher in IBD patients than controls (all p < 0.001): deliberate self-harm 1.31 (95% CI 1.16-1.47), anxiety 1.17 (1.11-1.24), depression 1.36 (1.31-1.42) and insomnia 1.62 (1.54-1.69). Patients with Crohn's disease were more likely to develop deliberate self-harm HR 1.51 (95% CI 1.28-1.78), anxiety 1.38 (1.16-1.65), depression 1.36 (1.26-1.47) and insomnia 1.74 (1.62-1.86). Patients with IBD are at increased risk of deliberate self-harm (HR 1.20 [1.07-1.35]). The incidence rate ratios of mental illnesses were particularly high during the first year following IBD diagnosis: anxiety 1.28 (1.13-1.46), depression 1.62 (1.48-1.77) and insomnia 1.99 (1.78-2.21). CONCLUSION: Deliberate self-harm, depression, anxiety and insomnia were more frequent among patients with IBD. IBD is independently associated with an increased risk of deliberate self-harm.