6 results on '"N O'Moráin"'
Search Results
2. P620 Can ustekinumab trough and antidrug antibody levels post induction predict treatment failure?
- Author
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M Mccrossan, N O’Moráin, L Kumar, C Rowan, J Sheridan, G Cullen, G Doherty, and H Mulcahy
- Subjects
Gastroenterology ,General Medicine - Abstract
Background Ustekinumab (UST), a monoclonal antibody that blocks interleukins IL-12 and IL-23, is increasingly used in the treatment of Crohn’s disease and Ulcerative Colitis. While therapeutic drug monitoring (TDM) is used with increasing frequency in other biologic agents, there is a paucity of data regarding the clinical utility of TDM for UST. This pilot study aimed to determine whether loss of response (LOR) and treatment failure (TF) can be predicted by post UST-induction serum trough concentrations and antibody levels. Methods A pilot retrospective observational study of patients who received subcutaneous (SC) induction of UST, following LOR to anti-TNF, for treatment of Crohn’s disease in 2016 was performed. We previously demonstrated comparable drug trough levels following SC rather than intravenous UST induction. Patients with available 74 month follow up data were included. Frozen serum samples used for this measurement were retrospectively tested for antibody levels using ELISA. Our IBD database and admissions data were analysed from 2016-2022. We recorded treatment duration, interval shortening, and treatment failure. Treatment failure was defined as switch to another biologic agent and/or surgery. Data were analysed using SPSS software [IBM], with Wilcoxon Rank Sum Test used for hypothesis testing. Results In this pilot study, a total of 10 patients (female=1, mean age 38.5 y) met the inclusion criteria. During the 74 month follow-up period, 3 patients failed treatment (mean age 30 y) while 7 remained on UST (mean age 42 y). All patients required interval shortening (4 weekly dosing). There was no difference in Crohn’s phenotype or smoking status between groups. All TF patients were switched to alternative biologic agents, with 1 patient requiring surgery. The patients who failed treatment were noted to have higher antibody levels (median 6.57 Au/ml vs 5.87 AU/ml, p=0.03) [Fig 1]. Two of these patients were noted to have lower trough levels than those who continued on UST, with one having a higher trough level (median 2.9mcg/ml vs 5.8mcg/ml, p=0.52) [Fig 2]. Conclusion Shortening of dose interval with UST therapy in Crohn’s disease is frequently required. This pilot study suggests an association between treatment failure and higher antidrug antibody levels 8 weeks post induction of UST. There was no significant difference in drug trough levels between groups. The patient with the highest trough level in the cohort failed treatment – This raises the possibility of multiple mechanisms of failure; however, it is impossible to draw conclusions given the sample size. Further studies are required to assess whether measurement of post induction antibody and drug trough levels has clinical utility in guiding treatment decisions.
- Published
- 2023
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3. Implementation of BSG/ACPGBI/PHE polypectomy surveillance guidelines safely reduces the burden of surveillance in a screening cohort: a virtual model study.
- Author
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Stack R, Doherty J, O'Moráin N, Nolan B, Sheridan J, Cullen G, Mulcahy H, Buckley M, Horgan G, Hamed M, McDermott E, and Doherty G
- Subjects
- Humans, Prospective Studies, Retrospective Studies, England, Colonoscopy, Gastroenterology
- Abstract
Objective: To evaluate the impact of British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE) 2019 polypectomy surveillance guidelines within a national faecal immunochemical test-based bowel cancer screening (BS) cohort on surveillance activity and detection of pathology by retrospective virtual application., Design: A retrospective review of BS colonoscopies performed in 2015-2016 with 5 years prospective follow-up in single institution. Index colonoscopies were selected. Incomplete colonoscopies were excluded. Histology of all resected polyps was reviewed. Surveillance intervals were calculated according to BSG/ACPGBI/PHE 2019 guidelines and compared with pre-existing 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis' (EUQA 2013). Total number of colonoscopies deferred by virtual implementation of BSG/ACPGBI/PHE 2019 guidelines were calculated. Pathology identified on procedures that would have been deferred was reviewed., Results: Total number of index BS colonoscopies performed in 2015-2016 inclusive was 890. 115 were excluded (22 no caecal intubation, 51 inadequate bowel preparation, 56 incomplete polyp clearance). N=509 colonoscopies were scheduled within a 5-year interval following index colonoscopy surveillance rounds based on EUQA guidelines. Overall, volume of surveillance was significantly reduced with retrospective application of BSG/ACPGBI/PHE 2019 guidelines (n=221, p<0.0001). No cancers were detected within the 'potentially deferred' procedures who attended for follow-up (n=330) with high-risk findings found in<10% (n=30) of colonoscopies within the BSG/ACPGBI/PHE cohort., Conclusion: BSG/ACPGBI/PHE 2019 guidelines safely reduce the burden of colonoscopy demand with acceptable pathology findings on deferred colonoscopies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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4. Rates and outcomes of testing for lynch syndrome in a national colorectal cancer screening programme.
- Author
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Cudmore J, Kumar L, O'Moráin N, Cullen G, Horgan G, Aird J, Sheahan K, Winter DC, Kennelly R, and Leyden J
- Subjects
- Humans, Early Detection of Cancer, Genetic Testing, DNA Mismatch Repair genetics, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms diagnosis, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Neoplastic Syndromes, Hereditary genetics
- Abstract
Background: Lynch Syndrome (LS), the most common cause of hereditary colorectal cancer (CRC), is characterised by pathogenic variants in mismatch repair (MMR) genes. Universal testing of all CRCs for LS can increase detection. Rates and outcomes of testing in Ireland's national CRC screening programme have not been examined previously., Methods: CRCs diagnosed at two screening sites between 2015 and 2020 were identified. Patient records were used to determine if CRCs had been tested for MMR deficiency and if detected, what downstream testing to rule out LS or genetic testing to confirm LS was undertaken., Results: Over five years, 206 CRCs were diagnosed. Testing for LS was carried out for 100% of CRCs at site A and 69% of CRCs at site B. Of CRCs tested for LS, 14 (8%) were MMR deficient. After downstream testing for BRAF mutation or hypermethylation of MLH1, three CRCs were identified as potentially LS-related. Of these two individuals declined genetic testing and one was lost to follow-up., Conclusions: By 2020 both sites had implemented universal testing of all CRCs for LS. A small number of individuals were identified as being eligible for genetic testing for LS, however those offered declined testing and one individual was lost to follow up. This highlights the importance of universal testing and the need for referral pathways to ensure all appropriate individuals are referred onwards to genetic services., Competing Interests: Declarations of interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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5. Faecal calprotectin as a potential biomarker of disease severity in SARS-CoV-2 infection.
- Author
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O'Moráin N, Stack R, Doherty J, Tosetto M, Garcia Leon A, Mallon P, and Doherty G
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- Biomarkers, Feces, Humans, SARS-CoV-2, Severity of Illness Index, COVID-19, Leukocyte L1 Antigen Complex
- Abstract
Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare.
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- 2022
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6. Mucosal Healing in Crohn's Disease: Bull's Eye or Bust? "The Pro Position".
- Author
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O'Moráin N, Doherty J, Stack R, and Doherty GA
- Abstract
Background: Crohn's disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications., Summary: Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge., Key Messages: Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)
- Published
- 2021
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