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Research outputs from the Gastroenterology department at the RD&E.


Recent Submissions

Now showing 1 - 5 of 159
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    Weight-Related Outcomes After Revisional Bariatric Surgery in Patients with Non-response After Sleeve Gastrectomy-a Systematic Review
    (Springer, 2023-07-01) Axer, S.; Lederhuber, H.; Stiede, F.; Szabo, E.; Näslund, I.
    Weight non-response after sleeve gastrectomy is an emerging issue. This systematic review compared revisional procedures for weight-related outcomes. We searched several databases for relevant articles and included adult patients with revisional bariatric procedures after primary sleeve gastrectomy. Twelve trials with 1046 patients were included, covering five revisional procedures. There were no randomised controlled trials, and 10 studies had a critical risk of bias. Significant variations in inclusion criteria, therapy benchmarks, follow-up schemes, and outcome measurements were observed, preventing meaningful comparison of results. Evidence-based treatment strategies for weight non-response after sleeve gastrectomy cannot be deduced from the current literature. Prospective studies with well-defined indications, standardised techniques, and strict adherence to outcome measurements are needed.
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    Whole blood DNA methylation changes are associated with anti-TNF drug concentration in patients with Crohn's disease
    (Oxford University Press, 2023-08-01) Lin, S.; Hannon, E.; Reppell, M.; Waring, J. F.; Smaoui, N.; Pivorunas, V.; Guay, H.; Chanchlani, N.; Bewshea, C.; Bai, B. Y. H.; Kennedy, N. A.; Goodhand, J. R.; Mill, J.; Ahmad, T.
    BACKGROUND AND AIMS: Anti-TNF treatment failure in patients with inflammatory bowel disease (IBD) is common and frequently related to low drug concentrations. In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14. METHODS: DNA methylation from 1,104 whole blood samples from 385 patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study were assessed using the Illumina EPIC Beadchip (v1.0) at baseline, weeks 14, 30 and 54. We compared DNA methylation profiles in anti-TNF-treated patients who experienced primary non-response at week 14 and if they were assessed at subsequent time points, were not in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 94), with patients who responded at week 14 and when assessed at subsequent time points, were in remission at week 30 or 54 (infliximab n = 99, adalimumab n = 93). RESULTS: Overall, between baseline and week 14, we observed 4,999 differentially methylated probes (DMPs) annotated to 2376 genes following anti-TNF treatment. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses.Epigenome-wide association (EWAS) analysis identified 323 DMPs annotated to 210 genes at baseline associated with higher anti-TNF drug concentrations at week 14. Of these, 125 DMPs demonstrated shared associations with other common traits (proportion of shared CpGs compared to DMPs) including body mass index (23.2%), followed by CRP (11.5%), smoking (7.4%), alcohol consumption per day (7.1%) and IBD type (6.8%). EWAS of primary non-response to anti-TNF identified 20 DMPs that were associated with both anti-TNF drug concentration and primary non-response to anti-TNF with a strong correlation of the coefficients (Spearman's rho = -0.94, p < 0.001). CONCLUSION: Baseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14 to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy.
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    Prevalence of NUDT15 genetic variants and incidence of thiopurine-induced leukopenia in Inflammatory Bowel Disease: A systematic review and meta-analysis
    (Oxford University Press, 2023-06-01) Yu, N.; Sriranganathan, D.; Walker, G. J.; Sazonovs, A.; Wilding, H.; Roberts, C.; Kennedy, N. A.; Ahmad, T.; Boyapati, R. K.; Ding, N. S.; Segal, J. P.
    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. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants, were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early (≤8 weeks) and late (>8 weeks) leukopenia, and relative risk of developing leukopenia. RESULTS: 20 studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C>T C/T diplotype was 13% (95% CI: 10-18%), *3/*3 c.415C>T T/T diplotype was 2% (95% CI: 1-2%), *1/*5 c.52G>A G/A diplotype was 2% (95% CI: 1-3%) and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% (95% CI: 4-12%). The pooled prevalence of *1/*3 was high in Japanese (20%, 95% CI: 16-24%) and Chinese patients (18%, 95% CI: 12-27%). The incidence of early leukopenia was 20% (95% CI: 16-26%) in *1/*3 patients, 99% (95% CI: 7-100%) in *3/*3 patients and 49% (95% CI: 29-69%) in *1/*6 patients. The incidence of late leukopenia was 36% (95% CI: 26-49%) in *1/*3 patients. CONCLUSIONS: NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations to guide thiopurine dosing and prevent myelotoxicity.
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    A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose
    (Springer, 2023-06-01) Kennedy, N. A.; Achebe, M. M.; Biggar, P.; Pöhlmann, J.; Pollock, R. F.
    BACKGROUND: Intravenous iron is the preferred treatment for patients with iron deficiency anemia in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions (HSRs) and, rarely, anaphylactic or anaphylactoid reactions. AIM: The objective of the present study was to systematically review the literature to identify and analyze data on the incidence of HSRs after administration of ferric derisomaltose (FDI) or ferric carboxymaltose (FCM). METHOD: A prospectively-registered systematic literature review was conducted to identify prospective randomized controlled trials comparing FDI and FCM with other intravenous iron formulations or oral iron. Searches were conducted in PubMed (including MEDLINE), EMBASE, and the Cochrane Library in November 2020. The relative incidence of serious or severe HSRs occurring on the day or day after dosing of intravenous iron, recorded under the standardized Medical Dictionary for Regulatory Activities query for anaphylactic reaction. RESULTS: Data were obtained from seven randomized controlled trials of FCM (N = 2683) and ten of FDI (N = 3474) enrolling 10,467 patients in total. The number of patients experiencing any serious or severe HSR event was 29/2683 (1.08%) with FCM versus 5/3474 with FDI (0.14%). Bayesian inference of proportions showed the event rates to be significantly lower with FDI relative to FCM. CONCLUSION: HSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM. Further large-scale, head-to-head trials of the iron formulations would be required to confirm this finding.
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    Establishing key performance indicators for inflammatory bowel disease in the UK
    (BMJ, 2023-05-25) Quraishi, M. N.; Dobson, E.; Ainley, R.; Din, S.; Wakeman, R.; Cummings, F.; Sebastian, S.; Bloom, S.; Limdi, J. K.; Dhar, A.; Speight, R. A.; Bodger, K.; Kennedy, N. A.; Lamb, C. A.; Arnott, I. D.; Selinger, C. P.
    BACKGROUND AND AIMS: Healthcare quality improvement (QI) is the systematic process to continuously improve the quality of care and outcomes for patients. The landmark Inflammatory Bowel Disease (IBD) UK National Audits provided a means to measure the variation in care, highlighting the need to define the standards of excellence in IBD care. Through a consensus approach, we aimed to establish key performance indicators (KPIs), providing reliable benchmarks for IBD care delivery in UK. METHODS: KPIs that measure critical aspects of a patient journey within an IBD service were identified though stakeholder meetings. A two-stage Delphi consensus was then conducted. The first involved a multidisciplinary team of IBD clinicians and patients to refine definitions and methodology. The second stage assessed feasibility and utility of the proposed QI process by surveying gastroenterology services across UK. RESULTS: First, the four proposed KPIs were refined and included time from primary care referral to diagnosis in secondary care, time to treatment recommendation following a diagnosis, appropriate use of steroids and advanced therapies prescreening and assessment. Second, the Delphi consensus reported >85% agreement on the feasibility of local adoption of the QI process and >75% agreement on the utility of benchmarking of the KPIs. CONCLUSIONS: Through a structured approach, we propose quantifiable KPIs for benchmarking to improve and reduce the individual variation in IBD care across the UK.