Introduction

There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. Our aim was to develop an IBD risk prediction tool to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes.

Aims & Methods

We developed and internally validated a risk prediction tool for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).
A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) database was undertaken between 1st January 2010 and 31st December 2019 of all the patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to IBD diagnosis. Candidate predictors were chosen based on clinical and substantive knowledge. Cox proportional hazards regression with backward elimination was used for model development of IBD, UC and CD risk prediction models. The predictive performance of the models was assessed using discrimination (C-statistic). Internal validation using 1000 bootstrap sampling repetitions was used to estimate the optimism-corrected measures of predictive performance.

Results

Of 2,056,398 patients with lower GI symptoms: 11,192 patients had an IBD diagnosis (7033 UC (62.8%) and 4138 CD (37.0%)). The final IBD model included demographic factors (age, sex, ethnicity, smoking, index of multiple deprivation, body mass index, Charlson comorbidity index, loperamide use) co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal (EIM) manifestations (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), laboratory investigations (low haemoglobin (Hb), low Mean Corpuscular volume (MCV), low albumin, low ferritin, raised C-reactive protein (CRP), raised Erythrocyte Sedimentation Rate (ESR), raised calprotectin level). The UC model included all above except mouth ulcers, IBS, ophthalmic EIM. Depression and ferritin were excluded in the CD model though low vitamin B12 level was included. The risk score for each patient was the sum of individual risk factors. In the development dataset, models showed moderate discrimination. For the IBD prediction tool: C-statistic 0.71 (95% CI 0.70-0.71),UC prediction tool: C-statistic 0.70 (95% CI 0.69-0.70) and CD prediction tool: C-statistic 0.75 (95% CI 0.74-0.76). The C-statistics of the models showed that the IBD, UC and CD prediction tools reliably differentiated patients with and without IBD,UC and CD respectively.

Conclusion

A risk score of patient demographics, symptoms and investigations performs well for IBD,UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

Disclosure

No conflict of interest to declare

Introduction

Initial reports suggested a high mortality associated with peri-operative COVID-19 infection resulting in delayed surgery and a global change in surgical pathways. The impact of COVID-19 variants and vaccinations on surgical outcomes is yet to be described.

Aims & Methods

We aimed to define the risk of COVID-19 infection in the 30 days following surgery and the associated mortality. With the approval of NHS England we identified all registered adult patients in an OpenSAFELY-TPP primary care general practice within England whilst having an abdominal, obstetric, orthopaedic, thoracic or vascular procedure defined using OPCS codes between 01/02/2020 and 01/03/2022.COVID vaccinations and COVID waves were defined. Crude 30 day risks were calculated using Kaplan Meier curves. A competing risks Cox proportional survival analysis was used to adjust the cumulative risk of COVID-19 infection by the competing risk of death and subsequent non COVID-19 emergency readmissions.
Primary care records managed by the GP software provider TPP were linked to ONS death data, Hospital Episodes Statistics, and Second Generation Surveillance System Public Health England test data through OpenSAFELY. All data were linked, stored and analysed securely within the OpenSAFELY platform: https://opensafely.org/. Data include pseudonymised data such as coded diagnoses, medications and physiological parameters. No free text data are included. All code is shared openly for review and re-use under MIT open license https://github.com/opensafely/PostOpCovid. Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared.
This study was approved by the Health Research Authority [REC reference 21/EE/0278] by the East of England Research Ethics Committee.

Results

We identified 1,213,890 patients within the study period who underwent at least one surgical procedure. Following surgery 11,950 (0.9%) patients developed COVID-19 infection within 30 days. Post-operative COVID infections were greatest in wave 4 with 2.5% of patients having a post-operative infection. Adjusting for all factors post-operative COVID infection risk was 4.9 (aHR 4.88 95% CI 4.65-5.12) fold greater in the fourth wave compared to the first wave.
Within 90 days of surgery there were 820 (0.06%) deaths. A recent COVID infection increased crude morality to 1.42%, and a post-operative COVID infection increased crude mortality to 1.82%. The risk of death reduced following a first and second vaccination (aHR 0.11 95% CI 0.09-0.13). A recent COVID infection (7-42 days prior to admission) increased mortality 4 fold (aHR 3.84 95% CI 3.31-4.45) and a post-operative COVID infection increased mortality 8 fold (aHR 8.49 95% CI 7.6-9.48) compared to those without a COVID-19 infection. This increased 90 day mortality risk was highest in the second wave following a post-operative COVID infection, but then decreased to the non-covid baseline for both emergency and elective procedures in the 3^rd and 4^th waves.

Conclusion

The risk of post-operative COVID infection is low but has increased as strains have been become more transmissible. The absolute risk of death following peri-operative COVID-19 infection is greater than those who have not had infection however this risk has become attenuated during the latter waves of the pandemic.

Acknowledgements: We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and the NHS England Transformation Directorate.

Disclosure

None to declare

Introduction

Sporadic neoplasias (SNs) and ulcerative colitis-associated neoplasias (UCANs) can occur in patients with UC. Differences in the characteristics and prognoses between UCANs in patients with UC and SNs in patients without UC have been assessed in numerous previous studies. However, only a few studies have focused on the characteristics and prognoses of SNs in patients with UC. It is important to distinguish between UCANs and SNs, because they have different prognoses and therefore need different treatment strategies.

Aims & Methods

This study aimed to evaluate the clinical features and prognoses of SNs detected in patients with UC, both within and outside the affected area. A total of 141 SNs in 59 patients with UC, which were detected by surveillance colonoscopy (SCS) at Hiroshima University Hospital between January 1999 and December 2021, were included. In our hospital, we perform SCS for UC patients with left-sided or total colitis and with a disease duration of more than 7 years, if possible, in the remission stage. SNs were diagnosed based on their location, endoscopic features, and histopathological findings. The final diagnosis was made by histopathological evaluation of the excised specimens and confirmed by more than one gastrointestinal pathologist. The histopathological diagnosis of SN was made according to the pathological features described in the recent European Crohn's and Colitis Organization and the European Society of Pathology statement on histopathology. Immunohistochemical evaluation of Ki67 and p53 was performed in all cases. SNs, especially sporadic adenomas, have regular neoplastic glands with low amounts of stroma, and rarely have a mixture of benign/dysplastic crypts. Although UCANs sometimes have a surrounding flat area with overexpression of p53, SNs have no such area and have a distinct border between the neoplastic glands and non-neoplastic mucosa. SNs have Ki67 expression mainly in the superficial zone and have low levels of p53 expression.

Results

The mean age at first SN detection was 58.8 years, and the mean duration of UC was 9.9 years. Male patients represented 64.4% of the enrolled patients. The most common type of UC was the total colitis type (47.5%). With regard to their clinical course, approximately half of the patients (49.2%) presented with the relapse-remitting type. Among the 141 SNs, 129 lesions (91.5%) were diagnosed as adenomas, five (3.5%) as Tis carcinomas, two (1.5%) as T1a carcinomas (superficially submucosal invasive carcinoma: <1,000 µm), and five (3.5%) as T1b carcinomas (deeply submucosal invasive carcinoma: ≥1,000 µm). There were 86 (61.0 %) SNs in the right colon, 44 (31.2%) in the left colon, and 11 (7.8%) in the rectum. When classified as outside or within the affected area of UC, 100 (70.9%) SNs occurred outside and 41 (29.1%) within. Most SNs (135 lesions, 95.7%) underwent endoscopic resection, and only six lesions (4.3%) underwent surgical resection. Among the 59 patients included in this study, synchronous SNs occurred in 14 (23.7%), and metachronous multiple SNs occurred in 24 (40.7%) patients. The 5-year cumulative incidence of metachronous multiple SNs was higher in patients with synchronous multiple SNs (54.2%) than in those without (46.4%). The histology, size, and background mucosa of the initial SNs were not associated with the incidence of metachronous SNs in our study.

Conclusion

UC patients with synchronous multiple SNs were at higher risk of developing metachronous multiple SNs and may require close follow-up compared to patients without synchronous SNs.

Introduction

Celiac disease (CeD) is a chronic, immune-mediated, systemic disorder characterized by inflammation of the small intestine and antibody formation in response to gluten ingestion. A gluten-free diet (GFD) has major limitations but is the only current treatment for CeD.

Aims & Methods

This US prospective observational study (Virtual Celiac Symptoms Study, NCT05309330) was conducted from July 25, 2022 to March 04, 2023 and aimed to assess experience with a GFD and celiac-related symptoms in patients with CeD. Eligible participants were aged ≥12 years, had a CeD diagnosis for ≥1 year confirmed via self-reported biopsy and serology (or serology only for participants diagnosed at age <18 years), were on a GFD for ≥6 months and reported CeD-related symptoms in the past 3 months. Participants were recruited with the assistance of the Celiac Disease Foundation via digital advertisements and data were collected using an electronic patient-reported outcomes platform. Study participants were followed up for 12 weeks and CeD-related symptoms and gluten exposure were assessed daily. Quality of life and healthcare resource utilization were also assessed. This analysis focuses on the adult participants’ perception of their disease experience at study initiation.

Results

The baseline questionnaires were completed by 338 adult participants. The median age was 37 years (range 18–71), 88% were female and 99% were White. CeD-related symptoms were reported by 58% of participants in the past week. When questioned about occurrence of CeD symptoms, 23% reported “Chronic/ongoing CeD symptoms even when I don't think I've been exposed to gluten”, 37% reported “CeD symptoms only while I am exposed to gluten or within a few days after exposure to gluten” and 36% reported “Chronic/ongoing CeD symptoms, but they are worse when I get exposed to gluten”. The most commonly reported symptoms were bloating (83%), tiredness (81%), abdominal pain (77%) and diarrhea (71%). All participants were following a GFD; 21% reported “never eating gluten accidentally or on purpose” and 71% reported “rarely eating gluten accidentally”. In total, 84% of participants reported that they were likely/extremely likely to experience CeD symptoms after gluten exposure. Symptom intensity was described as moderate or severe by 71% of participants, and 11% reported hospitalization or emergency department care due to CeD in the past year.

Conclusion

Despite high levels of reported adherence to a GFD, many patients still report CeD-related symptoms, especially in response to perceived gluten exposure. Symptoms were often reported as severe and over 10% reported a CeD-related hospitalization or emergency department visit in the past year. This ongoing study highlights the requirement for further understanding of persistent/recurrent symptoms and an unmet need for additional treatments for patients with CeD on a GFD.

Disclosure

LMM and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. JRM, SSe and SSu are employees of Analysis Group, Inc., which received research support from Takeda Development Center Americas, Inc. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda Development Center Americas, Inc. EL and DA serve as consultants for Takeda Pharmaceuticals.
Funding statement: This study was sponsored by Takeda Development Center Americas, Inc. Medical writing support was provided by Christina Nikolakopoulou, PhD, of Oxford PharmaGenesis, Oxford, UK and was funded by Takeda Pharmaceuticals.

Introduction

Making an Inflammatory Bowel Disease (IBD) diagnosis can be challenging as symptoms may mimic more common conditions such as irritable bowel syndrome or haemorrhoids. This can lead to delays in IBD diagnosis, which can be associated with the need for more complex treatment or surgery.

Aims & Methods

This study aims to quantify the time to diagnosis for IBD and examine associations with patient characteristics and faecal calprotectin (FC) and its impact on surgery and emergency hospital admissions.
A retrospective cohort study was conducted using Clinical Practice Research Datalink (CPRD AURUM) from 1st Jan 2007 to 31st Dec 2019. Adult patients were followed from when they first presented with symptoms, signs, test results or alternative diagnosis potentially related to IBD in primary care in the 3 year period prior to IBD diagnosis. The association between patient level factors and FC with the time to IBD diagnosis were examined using logistic regression analysis. We examined changes in time to IBD diagnosis over the 10 year study period. The association of time to IBD diagnosis with IBD related surgeries and emergency admissions was also examined.

Results

Of 28,092 IBD patients: 60.0% ulcerative colitis (UC) and 40.0% Crohn’s disease (CD). Median age 43(IQR 30-58) years; 51.9% female. Median time to diagnosis 15.6 (IQR 4.3- 28.1) months; UC 13.8 (3.2-27.1) months and CD 17.8 (6.5-29.2) months.
Factors associated with over 12 months to IBD diagnosis: female ((OR 1.64(95%CI 1.56-1.72)); Black (1.45(1.20-1.76)) or Asian ethnicity (1.55(1.40-1.72); older age compared to 18-30 years (>70 1.14(1.03-1.27)); obesity (1.09(1.01-1.17)); smoking (1.13(1.06-1.20)); lower socioeconomic status (1.15 (1.06-1.25)); anxiety (1.15(1.07-1.24)); depression (1.19(1.11-1.28)); non-steroidal anti-inflammatory drugs (NSAIDs) (1.45(1.33-1.59)); loperamide (1.56 (1.31-1.86)) and increasing comorbidity Charlson score >2 (1.46(1.32-1.61)).
Only 11.3% of IBD patients had FC testing. Time to diagnosis from FC date was median 4.0 (IQR 1.8- 8.8) months. Higher FC levels were associated with decreasing time to IBD diagnosis: 500-1000 (0.76 (0.66-0.89)),>1000 (0.61(0.51-0.72)).
No improvement in time to IBD diagnosis was observed over the last 10 years: 2010-2011 (14.4 (3.6 -27.6) months) compared to 2018-2019 median (15.6 (4.8-28.8) months).
Patients with time to diagnosis in highest quartile were at lower risk of surgery within a year of diagnosis (HR 0.91(0.81-1.03) but had more IBD related emergency admissions after diagnosis (IRR 1.06 (1.01-1.11).

Conclusion

Longer times to diagnoses were associated with females, minority ethnicities, increasing age, increasing comorbidity, deprivation, obesity, anxiety, depression, NSAIDs and loperamide use. Faecal calprotectin testing reduced time to diagnoses. Higher number of IBD related emergency admissions were observed in patients with a prolonged time to diagnosis.

Disclosure

No conflict of interest to declare

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.