Impact of direct-access IBD physician delivered endoscopy on clinical outcomes: a pre-implementation and post-implementation study.

Introduction: Patients with suspected inflammatory bowel disease (IBD) referred from primary care often face diagnostic and treatment delays. This study aimed to compare a novel direct-access IBD endoscopy pathway with the traditional care model. Method: Single centre real-world study analysing primary care referrals with suspected IBD. Group A: patients triaged to direct-access IBD endoscopy. Group B: patients undergoing traditional outpatient appointments before the availability of direct-access IBD endoscopy. Demographics, fecal calprotectin (FCP), C-reactive protein (CRP), disease activity score, endoscopy findings, treatment and follow-up were collected and statistically analysed. Ranked semantic analysis of IBD symptoms contained within referral letters was performed. Results: Referral letters did not differ significantly in Groups A and B. Demographic data, FCP and CRP values were similar. Referral to treatment time (RTT) at the time of IBD endoscopy was reduced from 177 days (Group B) to 24 days (Group A) (p<0.0001). Diagnostic yield of IBD was 35.6% (Group B) versus 62.0% (Group A) (p=0.0003). 89.2% of patients underwent colonoscopy in Group B versus 46.4% in Group A. DNA rates were similar in both groups. The direct to IBD endoscopy pathway saved 100% of initial IBD consultant clinics with a 2.5-fold increase in IBD nurse-led follow-up. Conclusion: Our novel pathway resulted in an 86% reduction in RTT with associated increased diagnostic yield while saving 100% of initial IBD consultant outpatient appointments. Replication in other trusts may improve patient experience and accelerate time to diagnosis/treatment while optimising the use of healthcare resources.

Transitioning from Intravenous to Subcutaneous Vedolizumab in Patients with Inflammatory Bowel Disease [TRAVELESS].

BACKGROUND AND AIMS: Subcutaneous [SC] vedolizumab presents the opportunity for inflammatory bowel disease [IBD] patients to manage their treatment at home. There are currently no data on the process of transitioning patients established on intravenous [IV] to SC vedolizumab as part of routine clinical care. The aim of this programme is to evaluate the clinical and biochemical outcomes of switching a cohort of IBD patients established on IV vedolizumab to SC, at 12 weeks following the transition. METHODS: In all, 178 adult patients were offered the opportunity to transition to SC vedolizumab. Patients who agreed were reviewed prior to switching and at Week 12 [W12] after their first SC dose. Evaluation outcomes included disease activity scores, the IBD-Control Patient-Reported Outcome Measures [PROMs], and faecal calprotectin [FCP]. Reasons for patients declining or accepting transitioning, pharmacokinetics, adverse drug reactions, and risk factors for a poor outcome in SARS-CoV-2 infection were also assessed. RESULTS: A total of 124 patients agreed to transition, of whom 106 patients had been on IV vedolizumab for at least 4 months. There were no statistically significant differences in disease activity scores or IBD-Control PROMs between baseline and W12. A statistically significant increase in FCP was observed [31 µg/g vs. 47 µg/g; p = 0.008], although this was unlikely to be clinically relevant. The most common adverse drug reaction reported was injection site reactions [15%]. Based on this cohort of patients, an expected reduction of £572,000 per annum is likely to be achieved. CONCLUSIONS: Transitioning patients established on IV vedolizumab to SC appears to be safe and effective, with high patient satisfaction and multiple benefits for the health service.

High incidence of glucocorticoid-induced hyperglycaemia in inflammatory bowel disease: metabolic and clinical predictors identified by machine learning.

BACKGROUND: Glucocorticosteroids (GC) are long-established, widely used agents for induction of remission in inflammatory bowel disease (IBD). Hyperglycaemia is a known complication of GC treatment with implications for morbidity and mortality. Published data on prevalence and risk factors for GC-induced hyperglycaemia in the IBD population are limited. We prospectively characterise this complication in our cohort, employing machine-learning methods to identify key predictors of risk. METHODS: We conducted a prospective observational study of IBD patients receiving intravenous hydrocortisone (IVH). Electronically triggered three times daily capillary blood glucose (CBG) monitoring was recorded alongside diabetes mellitus (DM) history, IBD biomarkers, nutritional and IBD clinical activity scores. Hyperglycaemia was defined as CBG ≥11.1 mmol/L and undiagnosed DM as glycated haemoglobin ≥48 mmol/mol. Random forest (RF) regression models were used to extract predictor-patterns present within the dataset. RESULTS: 94 consecutive IBD patients treated with IVH were included. 60% (56/94) of the cohort recorded an episode of hyperglycaemia, including 57% (50/88) of those with no history of DM, of which 19% (17/88) and 5% (4/88) recorded a CBG ≥14 mmol/L and ≥20 mmol/L, respectively. The RF models identified increased C-reactive protein (CRP) followed by a longer IBD duration as leading risk predictors for significant hyperglycaemia. CONCLUSION: Hyperglycaemia is common in IBD patients treated with intravenous GC. Therefore, CBG monitoring should be included in routine clinical practice. Machine learning methods can identify key risk factors for clinical complications. Steroid-sparing treatment strategies may be considered for those IBD patients with higher admission CRP and greater disease duration, who appear to be at the greatest risk of hyperglycaemia.

Life in lockdown: experiences of patients with IBD during COVID-19.

OBJECTIVE: COVID-19 has disrupted the normal way of life in the UK, but for some patients with inflammatory bowel disease (IBD), the impact of this unprecedented global emergency was far greater. We aimed to assess the experience of patients with IBD during the COVID-19 lockdown. DESIGN: We designed a survey focused on the impact of COVID-19 on IBD healthcare, social and psychological well-being and quality of life. To capture those most likely to be affected we targeted survey invitations at our British Society of Gastroenterology (BSG) defined high and moderate-risk IBD population. Access to the survey was also available via our trust's social media pages. RESULTS: 685 responses were received. 76% of respondents categorised themselves in BSG defined moderate or high-risk groups, requiring stringent social distancing or shielding. 87% did not change their IBD medication, with most reported changes initiated by the IBD team. 39% were worried about their IBD care, but most services were largely uninterrupted. 90% received 'at-risk' notification often from multiple sources, but 17% not until May. The majority reported a negative impact of COVID-19 on their quality of life and significantly increased perceived stress. Patients expressed a strong wish of having future care delivered remotely. CONCLUSION: COVID-19 has had a significant negative impact on psychological well-being of patients with IBD. Local IBD services must have a robust data set of vulnerable patients and be designated future responsibility for prompt communication of advice to avoid delayed and sometimes conflicting information. Remote patient management systems should be further developed and embedded in clinical practice.

Early real-world effectiveness of ustekinumab for Crohn's disease.

OBJECTIVE: To understand the effectiveness of ustekinumab in treating Crohn's disease (CD) in a UK real-world setting. DESIGN: Retrospective cohort study using prospectively maintained clinical records. SETTING: Single UK inflammatory bowel disease centre. PATIENTS: Adult patients with an established diagnosis of CD prescribed ustekinumab outside of clinical trials at University Hospital Southampton (UHS). INTERVENTIONS: Ustekinumab, a monoclonal antibody to the shared p40 subunit of interleukin (IL) 12 and IL-23 as part of routine clinical care. MAIN OUTCOME MEASURES: Effectiveness as measured by an improvement in physician's global assessment, drug persistence and improvement in biomarkers (C-reactive protein (CRP), albumin and calprotectin). RESULTS: 84 patients were included, 72 had a postinduction review and 49 had 1-year data. At postinduction clinical review, clinical response occurred in 53% of patients and clinical remission occurred in 8%. For patients on ustekinumab at 1 year, clinical response occurred in 71% and remission in 14%. Adverse events included four patients with infections requiring admission, one drug-related rash, five CD surgeries and two CD exacerbations. CONCLUSIONS: Ustekinumab was well tolerated in a complex UK CD population and demonstrated benefit to patients in terms of clinical response and improvement of biomarkers and with some patients attaining clinical remission. No unexpected safety signals were seen.

MicroRNA23a Overexpression in Crohn's Disease Targets Tumour Necrosis Factor Alpha Inhibitor Protein 3, Increasing Sensitivity to TNF and Modifying the Epithelial Barrier.

BACKGROUND AND AIMS: Mucosal healing is important in Crohn's disease therapies. Epithelial homeostasis becomes dysregulated in Crohn's, with increased permeability, inflammation, and diarrhoea. MicroRNAs are small non-coding RNAs that regulate gene expression and show changes in inflammatory bowel disease. Tumour necrosis factor alpha [TNFα] inhibitor protein 3 is raised in Crohn's and regulates TNFα-mediated activation of NFκB. We investigated TNFα regulation by microRNA in Crohn's disease [CD], and studied effects on epithelial permeability and inflammation. METHODS: Colonic epithelium from CD and healthy donor biopsies was isolated using laser capture microdissection, and microRNA was quantified. Tumour necrosis factor alpha inhibitor protein 3 was characterised immunohistochemically on serial sections. Expression effect of microRNA was confirmed with luciferase reporter assays. Functional barrier permeability studies and innate cytokine release were investigated with cell and explant culture studies. RESULTS: MicroRNA23a levels significantly increased in colonic Crohn's epithelium compared with healthy epithelium. Luciferase reporter assays in transfected epithelial cells confirmed that microRNA23a repressed expression via the 3' untranslated region of tumour necrosis factor alpha inhibitor protein 3 mRNA, coinciding with increased NFκB-mediated transcription. Immunohistochemical staining of TNFAIP3 protein in colonic biopsies was reduced or absent in adjacent Crohn's sections, correlating inversely with microRNA23a levels and encompassing some intercohort variation. Overexpression of microRNA23a increased epithelial barrier permeability in a colonic epithelial model and increased inflammatory cytokine release in cultured explant biopsies, mimicking Crohn's disease characteristics. CONCLUSIONS: MicroRNA23a overexpression in colonic Crohn's epithelium represses tumour necrosis factor alpha inhibitor protein 3, enhancing sensitivity to TNFα, with increased intestinal permeability and cytokine release.

Biological therapy for the treatment of prepouch ileitis: a retrospective observational study from three centers.

AIM: Prepouch ileitis (PPI) is inflammation of the ileum proximal to an ileoanal pouch, usually associated with pouchitis. The treatment of PPI as a specific entity has been poorly studied, but it is generally treated concurrently with pouchitis. This to our knowledge is the largest study to explore the efficacy of biologics for the specific treatment of PPI. METHODS: This was a retrospective observational study reporting outcomes following biological treatment in patients with PPI across three centers. Data were collected between January 2004 and February 2018 from two centers in the UK and one center in Italy. Outcomes included the continued presence of PPI following biologic therapy, pouch failure defined by the need for an ileostomy, and remission of PPI defined by the absence of any prepouch inflammation on endoscopic assessment within a year of biologic therapy. RESULTS: There were 29 patients in our cohort. On last endoscopic follow-up, 20/29 still had endoscopic evidence of PPI, seven had achieved endoscopic remission and avoided an ileostomy, and two had no endoscopic follow-up. In our cohort 11 patients had an ileostomy after a median time from starting a biologic of 25 months (range 14-91). CONCLUSION: Biologics fail to induce endoscopic remission of PPI in the majority of patients. Just under one-third patients with PPI coexistent with pouchitis can achieve endoscopic remission with biologics. In a large proportion of patients with PPI, surgery may be required despite biologic use.

Sniffing out causes of gastrointestinal disorders: a review of volatile metabolomic biomarkers.

Distinct changes can be observed in the odor of human excretions during health and disease. Identifying underlying volatile metabolites responsible for these odorous changes can be correlated with the pathological process within the body. Advances in the technology have enabled us to interpret the volatile signature of these changes in the odor. This has opened a promising area to lay the foundations of a rapid, noninvasive and point of care diagnostic tool. This review explores the diagnostic potential of volatile organic metabolites as novel biomarkers and extends the discussion on the clinical applications of these biomarkers in gastrointestinal disorders.

MicroRNAs in inflammatory bowel diseases: paradoxes and possibilities.

MicroRNAs (miRNAs) are single-stranded RNA molecules, which influence the translation of messenger RNA and hence protein synthesis. The altered expression of miRNAs in disease states in cancer and autoimmune diseases including inflammatory bowel disease is providing new insights into disease pathogenesis. This understanding is leading to consideration of the utility of miRNAs in diagnostics, prognostics, and therapeutics in inflammatory bowel disease. A literature search was conducted using the MEDLINE/PubMed databases using search terms inflammatory bowel disease, miRNA, treatment, and biomarkers.

A case of cerebral amyloid angiopathy.

UNLABELLED: BACKGROUND; Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid deposition in the walls of leptomeningal and cerebral cortical blood vessels. Clinically, CAA results in recurrent lobar haemorrhage that frequently presents with cognitive impairment or recurrent cerebral ischaemic events. CAA is widely believed to b eunder-diagnosed. CASE REPORT: An 84 year old patient presented with a history of recurrent unexplained collapses on a background of cognitive impairment. CT imaging of the brain demonstrated several lobar haemorrhages. In the absence of other causes of cerebral haemorrhage, the patient fulfilled the Boston diagnosis criteria for probable CAA. CONCLUSIONS: CAA should be considered in patients with multiple lobar haemorrhages, especially in the presence of cognitive impairment, and in the absence of other causes of cerebral haemorrhage such as trauma, space occupying lesion or a coagulopathy. The diagnosis of CAA is an important one because of the likely implication it has on future management targeted to reducing the future risk of further bleeding.