bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multisectoral approach and WHO ‘Bestbuys’ in Nigeria’s nutrition and physical activity policies
Authors: Oluwasanu Mojisola , Oladunni Opeyemi , Oladepo Oladimeji 
Published: January 2020

Abstract
Unhealthy diet and physical inactivity are modifiable risk factors for non-communicable diseases. Policies formulated in line with international guidelines are required for the implementation of population-level interventions to reduce the risks. This study describes the utilization of multisectoral approach (MSA) for the formulation of nutrition and physical activity policies and the extent to which they align with the WHO ‘Best Buy Interventions’. The research utilized a descriptive case study design and the theoretical model guiding the study was the Walt and Gilson framework for policy analysis. Data were obtained through the interview of 44 key informants using pre-tested guides and document review of 17 policies and articles obtained from government institutions or through the search of electronic databases. Data were integrated and analysed using thematic analysis. Between 2000 and 2016, Nigeria had formulated 10 nutrition-related policies and 5 guidelines with actions to promote physical activity. Only three nutrition and two physical activity policies adopted a high level of MSA. In line with the WHO best buy interventions, educational interventions for the general population are proposed to reduce sugar and salt intake and replace transfat with polyunsaturated fats but there are no legal regulatory acts to support these actions. Policy documents with actions to reduce physical inactivity do not include the WHO best buys. The country should adopt a wider range of actors to formulate and review policies, integrate all the WHO best buy interventions and develop effective legislation to regulate the salt and sugar content of processed foods.
Beyond an Anxiety Logic: A Critical Examination of Language Rights Cases before the European Court of Human Rights
Authors: Schmalz Dana 
Published: January 2020

Abstract
Language rights have traditionally been codified and discussed in the context of minority protection. The identification of language rights with questions of national minorities can, however, confound the analysis. This article explores the freedom of using a language and argues that the individual dimension of language rights must not be ignored beside the group dimension. The argument proceeds along a reading of three recent cases from the European Court of Human Rights, which concerned the use of Kurdish in Turkey. The Court’s reasoning illustrates the risk of an ‘anxiety logic’, which sees any language rights in connection with political claims of groups, thereby introducing additional conditions for the right and disregarding the significance a specific language can have for an individual, being more than a medium of conveying and receiving information. Conceptualising language use as an individual freedom is necessary also to account for situations other than national minorities, most importantly for the language rights of immigrants.
P096 DE NOVO COLITIS AFTER OCRELIZUMAB THERAPY
Authors: Akram Ali , Valasek Mark , Patel Derek 
Published: January 2020

Abstract

Introduction
Ocrelizumab is a humanized anti-CD20 monoclonal antibody approved for the treatment of adults with primary progressive or relapsing multiple sclerosis (MS). We report a case of de novo colitis in an MS patient who received a single dose of ocrelizumab.

Case report
A 62-year-old-male with primary progressive MS diagnosed in 2002, previously treated with corticosteroids, interferon beta-1a, and dimethyl fumarate, was admitted with 2 weeks of nonbloody diarrhea resulting in dehydration and weight loss. These symptoms began approximately 1 week after receiving a 300mg induction dose of ocrelizumab. Stool studies including culture, nucleic acid gastrointestinal pathogen panel and ova and parasite examination were negative. Stool fat stain was negative and fecal elastase was normal. Fecal calprotectin was markedly elevated, as were sedimentation rate (ESR) and c-reactive protein (CRP) (Table 1). CT of the abdomen and pelvis with intravenous contrast demonstrated pancolitis. Flexible sigmoidoscopy was performed and showed diffuse mucosal edema, loss of vascular pattern, granularity and multiple small ulcers to the proximal extent of the exam (Figure 1, Panel A). Biopsies confirmed moderately active colitis with mild architectural changes and mild plasmacytosis. Immunohistochemistry showed abundant CD3 cells with paucity of CD19 and CD 20 cells. The patient was treated with IV methylprednisolone with symptomatic improvement and was discharged on oral prednisone.
Two months after discharge (week 12 after ocrelizumab), diarrhea recurred during attempt to taper prednisone. Full colonoscopy at this time showed mild pancolitis with normal terminal ileum. Biopsies revealed minimally active colitis and new focal subepithelial collagen table thickening. Following multiple unsuccessful attempts to taper off of prednisone, extended release budesonide was started at week 41. This allowed for prednisone taper while maintaining symptomatic remission. Follow-up sigmoidoscopy at week 50 showed mucosal healing (Figure 1, Panel B); biopsies showed thickened subepithelial collagen layer typical of collagenous colitis.
The patient continues on budesonide at week 60; CD19 cell count remains undetectable (normal 6–23%).

Conclusion
To our knowledge, this is the first reported case of colitis associated with ocrelizumab therapy. Pertinent features include a) initial presentation with nonbloody diarrhea and endoscopic pancolitis with elevated ESR, CRP and fecal calprotectin, b) clinical response to prednisone and budesonide, and c) evolution into a collagenous colitis phenotype.
1 LOW RISK OF LYMPHOMA IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED USING ANTI-TUMOR NECROSIS FACTOR AGENTS
Authors: Egberg Matthew , Smitherman Andrew , Zhang Xian , Kappelman Michael 
Published: January 2020

Abstract

Background
Anti-Tumor Necrosis Factor (aTNF) agents are among the most effective medications used to treat pediatric inflammatory bowel diseases (pIBD). Despite their effectiveness, concerns regarding an association with lymphoma limit their use in everyday practice. We sought to determine the incidence rate and absolute risk of lymphoma in pIBD patients receiving aTNF treatment using a large, geographically diverse administrative insurance claims database.

Methods
We used the IQVIA Legacy PharMetrics Administrative Claims Database to identify pediatric (≤18 years) IBD patients (Crohn’s disease and ulcerative colitis) enrolled between 2007 and 2016. The IQVIA dataset contains enrollees’ clinical utilization, expenditures, and outpatient prescription information. We identified patient baseline data and medication exposure history over time to determine the incidence and absolute risk of lymphoma in our pIBD cohort.

Results
We identified 9,284 pIBD patients enrolled between 2007 and 2016, 62% with Crohn’s disease. The mean age of the cohort was 13.7 years (SD, 4.2) and comprised of 47% females. The median follow-up was 24 months (IQR, 33). Twenty-one percent of the cohort were treated with an aTNF agent during follow-up and 38% with an immune modulator (Thiopurine or Methotrexate). Nearly 8.5% were started on an aTNF agent while treated with an immune modulator, of which 90% were Thiopurines. We identified 3 cases of lymphoma occurring over 25,413 person-years of follow-up (Incidence rate, 11.8 cases/100,000 person-years). The absolute risk of lymphoma in our pIBD sample was 0.3 x 10–3. There were no cases of hepatosplenic T cell lymphoma observed. The medication exposure history for cases of lymphoma did not include treatment with an aTNF agent and/or an immune modulator.

Conclusion
Among our cohort of pIBD, the overall incidence and absolute risk of lymphoma were extremely low. Treatment with aTNF agents and/or immune modulators was not associated with an increased risk of malignancy. Our results would support prioritization of the clinical benefits of aTNF agents over the low risk for malignancy.
5 CREATION OF A CHRONIC PERIANAL CROHN’S FISTULA IN SWINE
Authors: Li Ling , Duraes Leonardo , Gearhart Susan , Zaheer Atif , Hu Haijie , Cheng Jiafei , Yao zhicheng , Donet Jean , Salem George , Mao Hai-quan , Selaru Florin , Parian Alyssa 
Published: January 2020

Abstract

Introduction
Perianal Crohn’s disease (PCD) is associated with worse outcomes including poor quality of life and higher medical costs. PCD is notoriously difficult to treat despite advancements in biologic therapies for luminal disease. In order to test innovative therapies for PCD, an animal model that closely mimics human perianal disease is warranted. Previous efforts were successful in creating perianal fistulas in swine, however, these closed after removal of the seton. A chronic model that maintains the fistula open and replicates the inflammatory component found in clinic is necessary.

Methods
Under general anesthesia, 4 female pigs underwent creation of surgical perianal fistulas using basic surgical technique with scalpel and hemostat. Size 24 French silicone foley catheter setons were placed to maintain patency of the fistula tract. Each pig had 3 fistulas created – 1 rectovaginal and 2 perianal. The setons were left in place for 4 weeks. After removal of the setons, Trinitrobenzenesulfonic acid (TNBS) was administered into the fistula tract twice a week to create local inflammation. After 2 weeks of TNBS, an MRI was obtained to assess the fistula tracts and the pigs were sacrificed to review histopathology.

Results
MRI showed successful creation of chronic fistula tracts, and maintenance of these tracts 2 weeks after removal of setons. We noted a transsphincteric fistula with supralevator component as well as an associated abscess 3.3 x 1.0 cm containing fluid and gas (Fig 1). Gross specimen revealed patent fistula tracts. Histopathology found significant chronic active inflammation on standard H&E staining (Fig 2).

Conclusions
A chronic perianal fistula model in pigs was successfully created using large bore rubber setons and TNBS stimulation that strongly resembles that seen in humans. Further studies are needed to standardize the conditions required to have a reproducible model with well-defined levels of inflammation, fistula patency, and other parameters.
P151 DISRUPTION OF ENDOGENOUS ITACONATE PRODUCTION EXACERBATES EXPERIMENTAL COLITIS
Authors: Frieler Ryan , Vigil Thomas , Mortensen Richard , Shah Yatrik 
Published: January 2020

Abstract

Background
Inflammation is a hallmark of inflammatory bowel disease and alterations in tricarboxylic acid cycle (TCA) metabolism have been identified as major regulators of immune cell phenotype during inflammation and hypoxia. The TCA cycle metabolite, itaconate, is produced by the enzyme aconitate decarboxylase 1 (Acod1) and is highly upregulated during classical macrophage activation and during experimental colitis. Itaconate and cell permeable derivatives have robust anti-inflammatory effects on macrophages, therefore we hypothesized that Acod1-produced itaconate has a protective, anti-inflammatory effect during experimental colitis.

Methods and Results
Wild type (WT) control and Acod1-/- mice were administered 3% Dextran Sulfate Sodium (DSS) in water for 7 days to induce experimental colitis. After DSS was discontinued, Acod1-/- mice had significantly reduced body weight recovery with increased macroscopic disease severity, and upon dissection had decreased colon length and more severe inflammation. To determine if myeloid cells are the critical Acod1/itaconate-producing cell types, we generated myeloid-specific Acod1 deficient mice, however no differences in weight loss, colon length or inflammatory gene expression were detected compared to WT controls. To test whether supplementation with exogenous itaconate could ameliorate colitis, WT mice were treated with the cell-permeable form of itaconate, dimethyl itaconate (DMI). Administration of DMI significantly improved recovery after 7 days of DSS treatment and significantly reduced inflammatory gene expression in the colon.

Conclusion
Our data suggest that Acod1-produced itaconate has an important role in the regulation of inflammation during experimental colitis. Although myeloid cells have been thought to be major producers of Acod1 and itaconate, our data indicate that other cell types are involved. These results highlight the importance of this immunometabolic pathway and suggest that preservation or enhancement of this pathway with natural metabolites or metabolite derivatives could have beneficial effects during colitis.
6 NOVEL BRD4 INHIBITORS BLOCK THE PATHOLOGICAL ACTIVATION OF BRD4-NFκB SIGNALING AND SUPPRESS COLONIC INFLAMMATION IN IBD MOUSE MODELS
Authors: Liu Zhiqing , Uribe Gabriela , Li Yi , Pingyuan Wang , Chen Haiying , Brasier Allan , Pinchuk Irina , Zhou Jia , Tian Bing 
Published: January 2020

Abstract
Ulcerative Colitis (UC) and Crohn’s Disease (CD) are two major types of inflammatory bowel disease (IBD), with recurrent symptoms and significant morbidity. Long-term persistence of chronic inflammation in IBD is among the major factors contributing to neoplastic transformation and development of colitis-associated colorectal cancer. There is a lack of efficient medications for IBD, due to either limited efficacy or side effects. Antibodies against TNFα are effective therapies; however, they are expensive, and up to 40% of patients are non-responders. Thus, improved therapy with higher efficacy, enhanced safety and better patient affordability is urgently needed.
The master regulator of innate immune response NFκB plays a critical role in the initiation and chronicity of IBD mucosal inflammation. We demonstrated that bromodomain-containing protein 4 (BRD4), an epigenetic reader, is required for stabilization of NFκB binding on the promoters of inflammatory genes, activation of RNA polymerase II, and histone H3 Lys122 acetylation (H3K122ac) to permit high levels of inflammatory gene expressions by sentinel epithelial cells and stromal fibroblasts. Our data using human IBD patient samples suggest that BRD4 activation is critical to the initiation of colonic inflammation.
We have successfully identified highly potent and specific BRD4 inhibitors, demonstrating that inhibition of BRD4 suppresses expression of inflammatory cytokines TNFα, IL-6, IL-17A, and IL-8. Administration of our lead inhibitors (ZL0454 & ZL0420) significantly reduces initiation of the mucosal inflammation in both dextran sulfate sodium (DSS)-induced and Cbir1 T cell transfer colitis models in vivo, but with low toxicity and much safer than the generic NFκB/IKK inhibitor BMS345541. The levels of NFkB and BRD4 activation were also compared using immunofluorescence staining of NFkB/RelA translocation, phospho-Ser276 RelA formation, and induction of the BRD4 marker H3K122Ac. The BRD4 inhibitors reduced DSS-induced NFkB-BRD4 activation in colon tissue, demonstrating the target specificity in vivo.
Our data suggest that BRD4 activation is critical to the initiation of the colonic inflammation during IBD. BRD4 inhibition disrupts its interactions with acetylated histone lysine residues, thereby blocking the pathological activation of the BRD4-NFκB signaling and suppressing colonic inflammation. Therefore, inhibition of the BRD4 activation is an attractive target for the development of novel IBD therapy and in prevention of CAC. Using our novel BRD4 inhibitors, we will further seek to evaluate the effect of long-term BRD4 inhibition on UC-induced neoplastic transformation and development of CAC.
Funding support: Crohn’s & Colitis Foundation Entrepreneurial Investing (EI) Initiative award and a research fellowship award from the Crohn’s & Colitis Foundation of America.
P070 TRENDS AND CHARACTERISTICS OF CLINICAL TRIALS PARTICIPATION IN THE IBD PARTNERS COHORT
Authors: Johnson Cole , Barnes Edward , Zhang Xian , Long Millie 
Published: January 2020

Abstract

Background and Aims
There are currently several recruitment challenges in randomized controlled trials (RCT) for inflammatory bowel disease (IBD) which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors which could influence future recruitment strategies.

Methods
We performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an interventional randomized controlled trial (RCT) of a medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated an in RCT during each calendar year from 2011–2018 and Clinicaltrials.gov was accessed to determine the number of active RCTs for IBD therapies per year during that same period.

Results
A total of 14,747 patients with IBD were included in the analysis and 1,116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation (Table 1) included following at an academic institution (OR=1.8; 95%CI: 1.51–2.04) and age 36–75 (OR=1.6; 95%CI: 1.43–1.87). Patients with Crohn’s disease (CD) were more likely to participate than those with ulcerative colitis (UC) (OR=1.5; 95%CI: 1.35–1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR=2.6; 95%CI: 2.19–2.99), IBD-related surgery (OR=2.5; 95%CI: 2.24–2.87), biologic exposure (OR=3.2; 95%CI: 2.76–3.65), and “Poor” or worse quality of life (OR=1.7; 95%CI: 1.45–1.93). Steroid-free remission was associated with lower likelihood of RCT participation (OR=0.6; 95%CI: 0.53–0.70). While the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort (Figure 1).

Conclusions
RCT participation rates declined within this cohort between 2011–2018. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean sCDAI and SCCAI scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-TNF exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.
P060 THE TREND OF DIAGNOSTIC COMPETENCY OF CROHN’S DISEASE IN THAI POPULATION FOR THE PAST TWO DECADES
Authors: Chaisidhivej Natapat , Aniwan Satimai , Pausawasdi Nonthalee , Limsrivilai Julajak 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) is an uncommon disease in Thai population, leading to delay in diagnosis due to lacking of familiarity, which may increase disease complications. One of the most problematic issues is to differentiate CD from intestinal tuberculosis (ITB), and many scoring systems have been introduced since 2006. However, competency of diagnosis of CD in the latter period is still unknown in Thailand. Our aim is to compare this competency in the period of 2000–2006, 2007–2012, and 2013–2018.

Methods
Retrospective study collecting all patients, whom diagnosed with CD in two tertiary referral centers in Bangkok, was performed. We focused the competency of diagnosis of each period by using the following variables; duration of presenting symptoms, number of colonoscopy before diagnosis, receiving anti-TB medication before diagnosis, and having first surgery before and at diagnosis. Comparison in each parameter was done by statistical analysis.

Results
A total of 190 CD patients were identified. Characteristics of patients were shown in Table 1. The patients were classified into 3 groups by using time period of diagnosis, which included 27, 62, and 101 patients in the 2000–2006, 2007–2012, and 2013–2018 period groups, respectively. Mean age was 38.6, 46, and 47.7 respectively. Nearly 50% were male, and 80% had inflammatory phenotypes in all groups. The median duration of presenting symptoms was 15.8, 10.1, and 11.7 months in the 2000–2006, 2007–2012, and 2013–2018 period groups, respectively (p=0.67). The percentage of patients receiving anti-TB medication before diagnosis was 19.2%, 9.8%, and 10.2%, in each group respectively (p=0.31). The number of colonoscopy for 1, 2, and &gt;2 times before diagnosis were 56.5%, 30.4%, and 13.1%; 55.7%, 24.6%, and 19.7%; and 41.7%, 38.5%, and 19.8% in each group, respectively (p=0.32). The percentage of patients undergoing first surgery before or at diagnosis were 33.3%, 21.0%, and 26.8%, respectively (p=0.80).

Conclusion
Competency in diagnosis of CD in Thailand has not changed in the past 2 decades. It is necessary to find effective methods helping physicians differentiate CD from other conditions to avoid the diagnosis delay, which may improve treatment outcomes.
P114 PERIANAL EXAMINATION AT TIME OF COLONOSCOPY - A MISSED OPPORTUNITY FOR IBD ASSESSMENT
Authors: Patel Rajan , Jameie-Oskooei Sina , Fromson Renate , Routledge Emma , Johnson Emma , Blad William , Wong Voishim 
Published: January 2020

Abstract

Introduction
The subtype of inflammatory bowel disease (IBD) is often not known at index colonoscopy and examining for perianal disease (PAD) can assist in establishing the diagnosis. PAD is common in Crohn’s disease (CD) but can also be seen in patients with ulcerative colitis (UC) in the form of fissures, abscesses and fistulae. Absence of perianal symptoms does not exclude PAD. Performing a routine perianal examination in a busy outpatient setting is not ideal and the endoscopy suite may be more appropriate. We hypothesise that perianal examinations are being omitted during IBD assessment colonoscopy.

Methods
Unisoft GI Reporting Tool was used to identify the last 70 consecutive CD and UC assessment colonoscopies performed over a 12 month period (August 2018 and July 2019) at a London-based district general hospital. Data was collected on demographics, known PAD, previous imaging and performance of perianal examination at colonoscopy.

Results
140 patients undergoing colonoscopy for IBD assessment were included in this study (70 CD, 70 UC).Median age 42 (IQR 32 – 55), Female 66 (47.1%).
15 (10.7%) had known perianal disease. Pelvic MRI had previously been performed in 20(14.3%). Perianal examination was performed in only 3 (2%) patients at the time of their last clinic consultation.
Although digital rectal examination (DRE) was performed in 132 (93.6%) of patients at the time of colonoscopy, only 9 (6.4%) had a perianal examination documented.

Conclusion
About 10% of patients in our cohort undergoing IBD assessment colonoscopy were known to have PAD but perianal examination was performed in only 2% of patients during clinic consultation and 6% during colonoscopy. Perianal examination at time of endoscopic assessment is an ideal setting to perform an intimate examination as you have an exposed, sedated and chaperoned patient. The omission of perianal examination at colonoscopy is a missed opportunity and improvement in this key element of disease assessment is required.