1,720,964 research outputs found
MicroRNA23a overexpression in Crohn’s Disease targets Tumour Necrosis Factor Alpha Inhibitor Protein 3, increasing sensitivity to TNF and modifying the epithelial barrier
No full textBackground 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.</p
P58 anonymous electronic IBD patient service feedback
No full textIntroduction: collecting structured patient feedback is challenging, particularly during the pandemic with many virtual appointments. Our electronic IBD-patient feedback covers outpatient (OP), endoscopy and flare-line experiences.Methods: IBD patients provide anonymous feedback at the time-of-service contact. GATHER, a survey platform hosted by our institution, collects anonymous information via QR codes (scan QR codes for surveys), electronic links or handheld tablet. Demographics, disease characteristics and medication were noted in all 3 surveys. The OP survey collated clinic type/modality and feedback on individual health care professionals based on an adapted Royal College of Physicians questionnaire as well as preferences for future appointments. Endoscopy surveys gathered information on referral pathway, endoscopy type, treatment advice, length of wait and pre-test information. Flare line surveys allowed individual feedback on IBD nurses, assessed response time and outcomes. Patients’ attitudes regarding use of our online portal My Medical Record (MyMR) were explored. All surveys allowed sign up for MyMR. Patients could leave individual comments.Results: since September 2021, 425 patients responded. Figure 1 outlines the findings of the surveys. [P58 Figure 1 not included].Conclusion: electronic surveys are well accepted by our IBD patients and provides useful demographic data. It gives patients the option to inform the service of their preferences for future appointments and allows clinicians to get personal patient feedback for appraisals. Furthermore, it provides feedback on new services such as direct access endoscopy service and the acceptability of patient directed online healthcare (MyMR). Patient-centred feedback enables the user to help shape their future local IBD service
O69 outcome of direct access IBD physician delivered endoscopy for general practice referrals with suspected IBD
No full textIntroduction: patients with suspected IBD referred by primary care (GP) are traditionally seen in gastroenterology outpatient clinics followed by endoscopic investigations. This 2 phase model leads to delay in diagnosis and treatment, increasing pressure on gastroenterology outpatient services while still requiring endoscopic intervention. Our novel pilot project compared outcomes between direct-access IBD physician-delivered endoscopy versus the traditional clinic model for patients with suspected IBD.Method: a prospective cohort of consecutive patients referred by GP with suspected IBD were triaged either direct to IBD endoscopy (n=50) or to outpatient IBD clinic followed by IBD endoscopy (n=50) at the discretion of 10 gastroenterology consultants grading GP referrals. Data on demographics, faecal calprotectin, C-reactive protein, endoscopy outcomes, treatment, and follow up was collected. (Group A = direct to IBD endoscopy and Group B = IBD endoscopy via IBD clinic).Results: both groups were age and gender-matched. Group A had a higher mean calprotectin (1363 ug/g vs 302 ug/g) and a higher C-reactive protein (10.6 mg/l vs 4.5 mg/l). In Group A only 38% had a full colonoscopy versus 86% in Group B. Definitive diagnosis and treatment at time of IBD endoscopy took 27 days in Group A versus 212 days in Group B. Treatment with immunomodulators and biologics was similar in both groups but mesalazine and steroid use was higher in Group A due to more severe disease and higher rate of ulcerative colitis, table 1 shows the diagnostic breakdowns from both groups following endoscopy. The IBD pick up was significantly higher in Group A with 70% vs 42%. Endoscopy DNA rate was twice as high in Group B (n=6). The direct to IBD endoscopy pathway resulted in 50 less initial IBD consultant clinics (100% reduction) with a follow-up shift from IBD consultant to IBD nurse clinics. [O69 Table 1 Diagnostic breakdown not included].Conclusion: triaging patients referred with suspected IBD directly to IBD physician delivered endoscopy resulted in more than a 26-week reduction in time to diagnosis and treatment while saving 100% of initial IBD consultant clinics. IBD pick up was high at 70% in direct to IBD endoscopy group, identifying a higher-need IBD population. Triaging GP referrals with suspected IBD direct to IBD endoscopy delivers rapid assessment and treatmen
P318 electronic referral grading system that puts patients and clinicians first
No full textIntroduction: the NHS Long Term Plan estimates demand for gastroenterology outpatient appointments (OPA) will continue to increase with the Royal College of Physicians deeming up to 20% of new referrals unnecessary. Bespoke electronic referral grading provides direct access to all community and hospital electronic patient records allowing fully informed immediate decision making. This can avoid unnecessary OPAs by redirecting/rejecting and sending appropriate patients direct-to-test while getting the right patient to the right clinician through sub-speciality tagging.Methods Outcomes: proportion/number of first OPA appointments saved, time to first appointment and subspecialty focus. Pre-grading period: Sep 2018–Mar 2020. Post-grading period: Aug 2020–Feb 2022. The separate 2WW IDA pathway was excluded. Cardiology/rheumatology were used as controls. Wait in days at the 50th percentile was calculated. One-tailed Mann Whitney U test calculated statistical significance at the p<0.05 level. Number of appointments saved per year and resultant financial implications were estimated.Results: GI received 3,768 consultant-graded referrals (Sep 2018–Mar 2020) and 3,908 (Aug 2020–Feb 2022).Referral sub-specialty groupings:1) Inflammatory Bowel Disease–765(19.6%)1. Irritable Bowel Syndrome–755(19.3%)2. Upper GI Diseases–753(19.3%)3. Non–IBD Colorectal–426(10.9%)4. Non–2WW Iron Deficiency Anaemia–345(8.8%)5. Unexplained Weight Loss–165(4.2%)6. Surgical/Hepatology–159(4.1%)7. Coeliac–139(3.6%)8. Endoscopy–126(3.2%)9. Complex Functional–106(2.7%)10. Not Tagged–88(2.3%)11. Intestinal Failure–81(2.1%)Documented referral rejection rates increased from 1% to 19% (n=745/3908) in the second period. 456 (11.6%) of patients were diverted directly to endoscopy, cumulatively saving 30.7% (n=1201) first OPA appointments equivalent to 150 new patient clinics. Total savings = £101,731/year in first GI OPA alone given the current block contract structure. Time to first appointment reduced by 58% but no improvement was seen in comparator specialties: [P318 Table 1Clinic wait times compared @ the 50th percentile not included]. Conclusions: use of a consultant-led electronic grading system had dramatic effects on the quality of data collected and significantly reduced first OPA waits at the trust. The reasons for this were triage direct-to-test and proactive rejection/redirection of referrals using sub-speciality tagging to get the right patient to the right clinician
Early real-world effectiveness of ustekinumab for Crohn's disease
No full textObjective: 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.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
- …
