bluuebunny/crossref_metadata_2025_split huggingface dataset:
N18 Facilitating involvement of patients from ethnic minority groups in research: experiences of offering patients a choice of interviewer
Authors: MUKHERJEE S , Beresford B 
Published: January 2020

Abstract

Background
Recruitment of inflammatory bowel disease (IBD) patients from an ethnic minority background to research is known to be very low. It has been suggested that interviewer characteristics may affect the willingness of individuals to take part in research, with some researchers advocating ethnicity and gender matching. A study on UK South Asian adults’ experiences of living with IBD provided an opportunity to explore these methodological issues further.

Methods
The study comprised qualitative interviews with adult patients with IBD identifying themselves as Indian/British Indian, Pakistani/British Pakistani, and Bangladeshi/British Bangladeshi. They were recruited from five clinics across England. Rather than presupposing what participants’ preferences might be, patients were offered a choice of interviewer in terms of the following characteristics: gender, shared experience (or not) of IBD, ethnicity and language (Bengali, Gujarati, Hindi, Mirpuri, Punjabi, Urdu). These interviewers were a particular type of ‘peer researcher’; distinctive in that they are a professional researchers and assumptions have not been made about the ‘peer’ characteristic which is most pertinent to study participants.

Results
Adopting this study design required strategic planning in terms of resources and research management. Recruitment to the study was good, with over 40% of those invited (n = 41) returning a response form indicating an interest in taking part. Some had no preference over who interviewed them (8 women, 6 men). Where a preference was expressed, gender was the most important factor. Almost all favoured a female rather than a male interviewer (12 vs. 1). The next most frequently requested option was for an interviewer with personal experience of IBD (n = 11). Very few prioritised the ethnicity of the interviewer. Of those that did, two also requested to be interviewed in a South Asian language. Involvement of ‘peer interviewers’ in the development of the interview guide led to the addition of research questions that would not otherwise have been included. In some interviews, shared experience (between interviewer and interviewee) increased the richness of data elicited which, on occasion, threatened ‘even-ess’ of emphasis across the dataset.

Conclusion
The study achieved an above average recruitment rate, the sampling frame was achieved, and rich data was generated. The research team intend to adopt a similar approach in future studies where it is anticipated recruitment to the study may be challenging and the topics for discussion are sensitive.
N20 The impact of inflammatory bowel disease-related fatigue on health-related quality of life: a qualitative semi-structured interview study
Authors: Radford S , Moran G W , Czuber-Dochan W 
Published: January 2020

Abstract

Background
Fatigue is a frequently reported symptom of inflammatory bowel disease (IBD), experienced by patients with active disease and in remission. Fatigue related to chronic conditions plays a significant negative role in Health-Related Quality of Life (HRQoL), but patients’ experience of this have not been researched in IBD. We aimed to explore experience of IBD fatigue and its impact on HRQoL in adults diagnosed with IBD.

Methods
Qualitative, semi-structured in-depth interviews were conducted with adults with IBD in remission, recruited from out-patient clinics in the UK. Eligibility and medical history were confirmed at recruitment. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was employed to analyse the data using NVivo 12 software.

Results
Fourteen participants (eight female, average age 37.3 years old, range 21–64) were interviewed. All identified as ‘White British’, average length of living with IBD fatigue was 10.9 years (range 9 months–17 years). Twelve participants reported constant fatigue and two reported intermittent fatigue. There were three key themes reflecting patient experiences: (1) ‘The new normal’ established through attempts to adapt daily life and acceptance of IBD fatigue impact on daily life and HRQoL. HRQoL is negatively impacted by lack of feelings of fulfilment, not being able to continue on as before the onset of IBD fatigue and a negative perception of self in comparison to others without IBD fatigue; (2) ‘Energy as a resource’ describes participants attempts to better manage fatigue on a daily basis through planning and prioritising tasks, often prioritising employment or education over social or leisure activities; (3) ‘Keeping healthy’ encompasses participants beliefs that good nutrition, good general health and keeping active allow them to generate energy more easily allowing some situational control where they have little control over IBD symptoms, subsequently improving HRQoL. Participants reported a mix of physical activities that improved HRQoL; however, none reported a specific programme of exercise.

Conclusion
Adults with IBD fatigue try to establish a sense of ‘new’ normality, through maintaining the same or similar, level of activities related to employment or education. However, this is often at the expense of personal, social and leisure activities. The study also indicates that perceptions of conservation of energy through planning and prioritising tasks and high levels of social support were associated with better self-reported HRQoL. Further research is required to explore physical activity-based intervention in relation to IBD fatigue, with use of validated fatigue and HRQoL measures.
DOP62 Morbidity after primary ileocecal resection for Crohn’s disease in the years of biologics: Lesson learned over 631 patients exclusively treated in a tertiary centre
Authors: Rottoli M , Tanzanu M , Vago G , Belvedere A , Parlanti D , Pezzuto P , Bosi S , Caputo F , Rizzello F , Gionchetti P , Poggioli G 
Published: January 2020

Abstract

Background
Several risk factors for morbidity after surgery for Crohn’s disease of the terminal ileum have already been identified. However, the study population is rarely homogeneous, due to high-volume centres receiving patients treated in other hospitals with diverging medical protocols and different thresholds for surgical referral. A study including only patients undergoing homogeneous perioperative treatment in a single referral centre might reduce the selection bias. The aim of this study was to identify the risk factors for minor (Clavien-Dindo ≤2) and major (Clavien-Dindo ≥3) postoperative complications in patients who received medical treatment and surgery in a single centre.

Methods
Retrospective analysis of ileocecal resections for Crohn’s disease in biological era (2004–2019). Recurrence was excluded. Risk factors for minor and major complications were identified through univariate and multivariable logistic regression analyses. Variables were selected by univariate analysis with p &lt; 0.2 criteria, then a stepwise selection with entry criteria p = 0.05 and stay criteria p = 0.1.

Results
Of 631 patients included (59.4% male, median age 37 years), 214 (34%) had previous surgery and 152 (24.1%) biologics. Laparoscopy was feasible in 35.9% of cases, 285 patients (45.1%) required surgery on other bowel sites due to multiple locations or fistulae. 281 (44.5%) patients presented with fistulizing disease.
Risk factors for 90-day minor complications (22.8%).
Risk factors for 90-day major complications (6.8%).

Conclusion
Risk of minor complications was higher in younger patients, especially after a longer medical treatment. Fistulating disease increases the risks only if the rectum and sigmoid colon are involved. Major complications seem to be related to specific patient’s comorbidities, rather than disease characteristics. Onset of hypertension and neuro-vascular disease, known adverse events of chronic steroid use, should not be underestimated in the preoperative assessment of patients. Poor nutritional status greatly increased the risk of minor and major complications; therefore, any effort should be made towards the nutritional optimisation of Crohn’s patients
N31 What factors affect quality of life and psychological well-being in patients with intestinal failure? A systematic review of quantitative studies
Authors: Roberts D , Liu Q , Czuber-Dochan W , Smith P , Norton C 
Published: January 2020

Abstract

Background
The most common cause of intestinal failure (IF) is Crohn’s disease (CD). The definition of IF is ‘the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth’. It is a result of the most severe phenotype of CD, where an individual can no longer obtain sufficient nutrients and fluids from their gut to sustain life without supplementation in the form of parenteral nutrition (PN) or intravenous fluids. Home PN (HPN) allows people to receive infusion at home and increases survival rates (65% after 6 years). Whilst HPN improves length of life, studies have demonstrated this treatment can severely negatively affect an individuals’ quality of life (QoL) and employment. The aim of this systematic review was to identify factors affecting QoL in people with IF.

Methods
A search of databases MEDLINE, PubMed, PsycINFO, Web of Science, Global Health, and Scopus was conducted in July 2019. Search terms included ‘Crohn’s disease’, ‘short bowel syndrome’, ‘intestinal failure’, ‘quality of life’, and ‘health-related quality of life’. Titles and abstracts were screened by one reviewer. Any uncertainties about inclusion of the papers were discussed with two reviewers. Full texts were screened by 3 reviewers. Quantitative studies that measured QoL as an outcome in people with IF were included.

Results
Nineteen studies including a total of 924 participants met the inclusion criteria. Six key themes of factors affecting QoL were identified: (1) Practicalities of IF and HPN, e.g. sleep disturbances from the noise of the pump; managing a high output stoma. (2) Impact of medical interventions, e.g. blood tests. (3) Social impact/physical activity/personal relationships, e.g. restricted ability to travel, socialise and eat with friends. (4) Personal and sexual impact, e.g. lack of sexual desire. (5) Impact of symptoms, e.g. fatigue. (6) Patient characteristics, e.g. age. Some studies also reported positive effects on health (such as more energy), improved symptoms and QoL with HPN, especially for those who had been very unwell previously.

Conclusion
People with IF often have poor QoL that is affected by many factors, from their symptoms to practical aspects of HPN. However, themes related to the ‘social’ and ‘personal’ impact of IF dominated in the literature. While there is considerable evidence on what affects QoL in people with IF, there appears to very little research on attempting to improve QoL in this patient group.
DOP64 Discovery of highly selective small-molecule oral inhibitors of integrin α4β7 for the treatment of inflammatory bowel diseases
Authors: WONG J , Bursavich M , Blanco N , Camblin A , Cappellucci L , Cohen R , Cui D , Krumpoch M , Zhong C , Hahn K , Lee D , Lippa B , Lin F Y , Lugovsky A , McShea M , Mostafavi S , Moy T , Sullivan A , Troast D , Wang L , Rogers B 
Published: January 2020

Abstract

Background
Integrins play a key role in facilitating immune cell trafficking throughout the body and represent an important receptor family for therapeutic intervention. In particular, the α4β7 integrin is a clinically validated target for the treatment of inflammatory bowel diseases (IBD), as exemplified by the humanised monoclonal antibody vedolizumab, which blocks the interactions between α4β7-expressing lymphocytes and its ligand MAdCAM-1. This blockade leads to the inhibition of these circulating lymphocytes from exiting the bloodstream and entering intestinal mucosal tissues resulting in a decrease in mucosal inflammation in patients. While oral inhibitors of the α4β7 integrin are advantageous over biologics, the efforts have been impeded by challenges to achieve desired selectivity and optimal DMPK properties. The aim of this study was to develop and characterise orally bioavailable small-molecule inhibitors of the α4β7 integrin and to determine their therapeutic potential.

Methods
Oral small-molecule inhibitors targeting the α4β7 integrin were discovered using Morphic Integrin Technology (MInT) platform. These small-molecule inhibitors were tested for potency and selectivity against a broad panel of integrin family members in multiple biochemical and cell-based functional assays in a ligand-competitive fashion. An acute PD assay with CFSE-labelled lymphocytes was developed to evaluate the activity of the small-molecule compounds in blocking lymphocyte trafficking to gut-associated lymphoid tissues in mice. The in vivo activity was also examined through changes in circulating α4β7+ CD4+ T memory cells in a relevant non-human primate model.

Results
Key drug candidate small molecules demonstrated over 1000-fold selectivity in vitro against a broad panel of integrin family members, including the α4β1 integrin. These compounds effectively blocked lymphocyte trafficking to mesenteric lymph nodes and Peyer’s patches in the gut in a dose-dependent manner, similar to an α4β7-specific antibody, in an acute gut-homing assay in mice. Additionally, these inhibitors also demonstrated effective occlusion of immune trafficking in a relevant non-human primate model. The lead compound has favourable DMPK properties, good oral bioavailability and is projected to have sufficient exposure in humans to effectively block α4β7-expressing immune cells in circulation.

Conclusion
Potent, selective, oral small-molecule inhibitors of α4β7 integrin have been discovered that demonstrate on-target, mechanistic efficacy in two animal models relevant to human IBD. It has the potential to be an effective and safe therapeutic in monotherapy as well as serving as a backbone for combination with other IBD drugs.
DOP66 A CEACAM5 small peptide restores the suppressive activity of CD8 + T cells in patients with Crohn’s disease
Authors: Roda G , Dunkin D , Correale C , Vetrano S , Merlino F , Marinelli L , Novellino E , Mayer L , Yeretssian G , Danese S 
Published: January 2020

Abstract

Background
Intestinal epithelial cells (IECs) play a pivotal role in controlling immune responses by activation of suppressive CD8+ T regulatory cells (Treg). In Crohn’s disease (CD) this response is impaired due to a defect in CEACAM5 expression on IECs. We previously identified a small region in CEACAM5 able to restore the impaired suppressive activity of CD8+ Treg cells in CD. Here, we tested the functionality of this small peptide in CD patients and evaluated its conformational structure to understand its interaction with T cells.

Methods
Suppression assays were done to assess the ability of peripheral blood (PB) CD8+ T cells isolated from healthy individuals and CD patients and stimulated with the small CEACAM5 peptide to suppress proliferation of activated CD4+ T cells. To understand the role of the Asparagine (N)71 residue present in the CEACAM5 small peptide, which has previously been shown to be pivotal for CD8+ T cell binding to CEACAM5, we tested a library of overlapping peptides in the same region as the small CEACAM5 peptide. Cytokine assays were performed to characterise CEACAM5 peptide-activated CD8+ T cells.

Results
CEACAM5 small peptide activated PB CD8+ T cells from CD patients significantly suppressed CD4+ T-cell proliferation. A new small peptide from the overlapping peptide library containing N71 induced the strongest suppression of proliferation. Peripheral CD8+ T cells produced increased interleukin (IL)-10 upon stimulation with the CEACAM5 peptide.

Conclusion
Our study offers a new approach for modulating the inflammatory state in CD by enhancing the suppressive function of CD8+ T cells using a CEACAM5 small peptide.
DOP67 CKD-506, a selective histone deacetylase (HDAC) 6 inhibitor, ameliorates colitis through regulation of NF-kB and AP-1 signalling pathway
Authors: Shin J , Ha N , Bae D , Lee Y J , Choi Y I , Ryu K H , Youn G S , Park J 
Published: January 2020

Abstract

Background
HDAC6 is a stress-inducible gene and highly expressed in pathological conditions as well as inflammatory bowel disease. Immuno-modulatory functions of HDAC6 inhibitors are well established and proposed therapeutic effects for autoimmune diseases through regulation of Treg cell function and inflammation. Moreover, HDAC6 inhibitors regulate inflammatory cytokines and chemokines, neutrophil activities, and epithelial regeneration in colitis models. CKD-506, a potent and selective oral HDAC6 inhibitor, is generally safe and well-tolerated in human, and is now investigating the efficacy in patients with rheumatoid arthritis. Herein, for future investigation with IBD, we identified molecular action mechanisms of CKD-506 involved in anti-colitis effects.

Methods
Mouse peritoneal macrophages or Raw264.7 cells were transfected with HDAC6 overexpression plasmid or empty vector as control. Cells were cultured in the presence or absence of 0.03~3 μM CKD-506, and the expression and production of inflammatory mediators were determined by RT–PCR and ELISA respectively. For reporter assays, Raw264.7 cells were transfected with pNF-kB-luc or pAP-1-luc plasmid and luciferase activity in cell lysates was determined by a luminometer. Signalling molecules in HDAC6 overexpressed cells were checked by immunoblot analysis. For the efficacy test of CKD-506, we used DSS-, TNBS-, Piroxicam (IL-10−/−)-, and adaptive T-cell transfer (RAG1−/−)-mediated colitis animal models. Colitis animals were treated with 1 to 100 mg/kg of CKD-506 and analysed disease activities and inflammatory mediators.

Results
In vivo, CKD-506 strongly inhibited disease activities in DSS-, TNBS-, Piroxicam-, and adaptive T-cell transfer-mediated colitis. In the chemical-induced colitis model, the expression of cell adhesion molecules and chemokines such as IP-10 and also infiltration of immune cells to colon tissues were reduced in CKD-506 treated mice. In vitro, HDAC6 overexpression strongly induced ROS and NADPH oxidase activity in Raw264.7 cells and CKD-506 significantly and dose-dependently inhibited HDAC6-mediated ROS and NADPH activity. Moreover, CKD-506 inhibited the production of pro-inflammatory cytokines and chemokines which are up-regulated in HDAC6 overexpressed mouse peritoneal macrophages or Raw264.7 cells. In promoter assay, HDAC6 overexpression highly induced NF-kB and AP-1 activity and CKD-506 strongly and dose-dependently inhibited both signalling pathways.

Conclusion
These data provide insight that CKD-506, a selective HDAC6 inhibitor, has anti-inflammatory and anti-colitis effects through regulation of NF-kB and AP-1 signalling pathway. Therefore, CKD-506 may provide beneficial effects in patients with Crohn’s disease and ulcerative colitis.
DOP77 Ustekinumab is associated with better effectiveness outcomes when compared with vedolizumab in Crohn’s disease patients with prior anti-TNF failure: comparative effectiveness study from the ICC Registry
Authors: Biemans drs V , van der Woude J , Dijkstra G , van der Meulen- de Jong A , Löwenberg M , de Boer N , Oldenburg B , Srivastava N , Jansen J , Bodelier A , West R , de Vries A , Haans J , de Jong D , Hoentjen F , Pierik M 
Published: January 2020

Abstract

Background
Both vedolizumab and ustekinumab can be considered for the treatment of Crohn’s disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or planned in the near future. The aim of this study was to compare vedolizumab and ustekinumab in CD patients using a quasi-experimental study design in a prospective registry specifically developed for comparative studies.

Methods
CD patients who failed anti-TNF treatment and started vedolizumab or ustekinumab in standard care as second-line biological and naïve to the latter two therapies, were identified in the observational prospective ICC Registry. Corticosteroid-free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C-reactive protein ≤5 mg/l and faecal calprotectin ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression (correcting for current smoker, disease duration, complicated disease (stricturing or penetrating behaviour), prior CD-related surgery, number of prior anti-TNF treatments, HBI at baseline and biochemical disease at baseline) and propensity score matching (variables include the same variables as logistic regression analysis with addition of disease location and behaviour, corticosteroid and immunosuppressant use at baseline).

Results
In total, 128 vedolizumab- and 85 ustekinumab-treated patients fulfilled the inclusion criteria. By using propensity score matching, 69 vedolizumab-treated patients were matched with 69 ustekinumab-treated patients. After adjusting for confounders, ustekinumab-treated patients were more likely to achieve corticosteroid-free clinical remission (OR: 2.56, 95% CI: 1.35–4.87, p = 0.004), biochemical remission (OR: 2.22, 95% CI: 1.04–4.74, p = 0.040), and combined corticosteroid-free clinical and biochemical remission (OR: 2.58, 95% CI: 1.15–5.78, p = 0.022), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63–2.54, p = 0.517; adverse events: OR: 1.33, 95% CI: 0.62–2.81, p = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32–1.39, p = 0.282) were comparable between the two groups. The propensity score matched cohort showed comparable results.

Conclusion
In this prospective, comparative analysis ustekinumab was associated with higher effectiveness outcomes of ustekinumab when compared with vedolizumab. Safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti-TNF treatment.