A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitis.

Background: An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient's disease course.

Aims: To derive a personalised algorithm for identifying patients at high risk of corticosteroid non-response from variables available at hospital presentation using a large prospectively collected acute UC patient database and machine learning-based techniques.

Methods: We analysed data from 682 consecutive presentations of acute UC.

Switching from Dose-Intensified intravenous to SubCutaneoUS infliximab in Inflammatory Bowel Disease (DISCUS-IBD): protocol for a multicentre randomised controlled trial.

Introduction: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab.

Speech patterns in responses to questions asked by an intelligent virtual agent can help to distinguish between people with early stage neurodegenerative disorders and healthy controls.

Previous research has provided strong evidence that speech patterns can help to distinguish between people with early stage neurodegenerative disorders (ND) and healthy controls. This study examined speech patterns in responses to questions asked by an intelligent virtual agent (IVA): a talking head on a computer which asks pre-recorded questions. The study investigated whether measures of response length, speech rate and pausing in responses to questions asked by an IVA help to distinguish between healthy control participants and people diagnosed with Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD).

Safety, Effectiveness, and Treatment Persistence of Subcutaneous Vedolizumab in IBD: A Multicenter Study From the United Kingdom.

Background And Aims: Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking.

Methods: IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment.

Prevalence of NUDT15 Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Background And Aims: Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.

Methods: Six databases were searched from inception until July 2022.

Treatment adaptations and outcomes of patients experiencing inflammatory bowel disease flares during the early COVID-19 pandemic: the PREPARE-IBD multicentre cohort study.

Background: The COVID-19 pandemic offered a unique opportunity to understand inflammatory bowel disease (IBD) management during unexpected disruption. This could help to guide practice overall.

Aims: To compare prescribing behaviour for IBD flares and outcomes during the early pandemic with pre-pandemic findings METHODS: We performed an observational cohort study comprising patients who contacted IBD teams for symptomatic flares between March and June 2020 in 60 National Health Service trusts in the United Kingdom.

Ambulatory care management of 69 patients with acute severe ulcerative colitis in comparison to 695 inpatients: insights from a multicentre UK cohort study.

Introduction: Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts.

Aims: We used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.

Inflammatory Bowel Disease Clinical Activity is Associated with COVID-19 Severity Especially in Younger Patients.

Background And Aims: Age is a major prognostic factor for COVID-19 outcomes. The effect of inflammatory bowel disease [IBD] activity on COVID-19 is unclear. We examined the relationship between IBD activity and COVID-19 severity according to age.

Letter: risk of severe COVID-19 outcomes associated with inflammatory bowel disease medications-reassuring insights from the United Kingdom PREPARE-IBD multicentre cohort study.

LINKED CONTENT This article is linked to Taxonera et al paper. To view this article, visit https://doi.org/10.

Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study.

Background: There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes.

Methods: The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK.

Incidence and prevalence of inflammatory bowel disease in Devon, UK.

Background And Aims: We sought to define temporal changes in prevalence of inflammatory bowel disease (IBD) in East Devon, UK, in order to facilitate service planning over the next 5 years.

Methods: Multiple primary and secondary care databases were used to identify and verify cases. Point prevalence and incidence of IBD were reported in April 2017 and from 2008 to 2016, respectively.

Quality improvement project identifies factors associated with delay in IBD diagnosis.

Background: Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking.

Aim: To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD.

Methods: This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services.

Characterising spoken responses to an intelligent virtual agent by persons with mild cognitive impairment.

The diagnosis of Mild Cognitive Impairment (MCI) characterises patients at risk of dementia and may provide an opportunity for disease-modifying interventions. Identifying persons with MCI (PwMCI) from adults of a similar age without cognitive complaints is a significant challenge. The main aims of this study were to determine whether generic speech differences were evident between PwMCI and healthy controls (HC), whether such differences were identifiable in responses to recent or remote memory questions, and to determine which speech variables showed the clearest between-group differences.

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 to 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 exposure.

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.

Massively parallel variant characterization identifies alleles associated with thiopurine toxicity.

As a prototype of genomics-guided precision medicine, individualized thiopurine dosing based on pharmacogenetics is a highly effective way to mitigate hematopoietic toxicity of this class of drugs. Recently, deficiency was identified as a genetic cause of thiopurine toxicity, and -informed preemptive dose reduction was quickly adopted in clinical settings. To exhaustively identify pharmacogenetic variants in this gene, we developed massively parallel NUDT15 function assays to determine the variants' effect on protein abundance and thiopurine cytotoxicity.

HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease.

Background & Aims: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.

Methods: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy.

Genome-Wide Association Study of Microscopic Colitis in the UK Biobank Confirms Immune-Related Pathogenesis.

Background And Aims: The causes of microscopic colitis are currently poorly understood. Previous reports have found clinical associations with coeliac disease and genetic associations at the human leukocyte antigen [HLA] locus on the ancestral 8.1 haplotype.

Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study.

Background: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal.

Methods: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study.

Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease.

Importance: Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM).

On the intersection of phonetic detail and the organization of interaction: clinical connections.

The analysis of language use in real-world contexts poses particular methodological challenges. We codify responses to these challenges as a series of methodological imperatives. To demonstrate the relevance of these imperatives to clinical investigation, we present analyses of single episodes of interaction where one participant has a speech and/or language impairment: atypical prosody, echolalia and dysarthria.

Coordination and interpretation of vocal and visible resources: 'trail-off' conjunctions.

The empirical focus of this paper is a conversational turn-taking phenomenon in which conjunctions produced immediately after a point of possible syntactic and pragmatic completion are treated by co-participants as points of possible completion and transition relevance. The data for this study are audio-video recordings of 5 unscripted face-to-face interactions involving native speakers of US English, yielding 28 'trail-off' conjunctions. Detailed sequential analysis of talk is combined with analysis of visible features (including gaze, posture, gesture and involvement with material objects) and technical phonetic analysis.