bluuebunny/crossref_metadata_2025_split huggingface dataset:
P075 SER-287, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC, INDUCES WIDESPREAD METABOLOMIC AND HOST TRANSCRIPTIONAL CHANGES RELATED TO CLINICAL REMISSION IN PATIENTS WITH ACTIVE MILD-TO-MODERATE ULCERATIVE COLITIS
Authors: Diao Liyang , O’Brien Edward , Ford Christopher , Wortman Jennifer , Aunins John , Henn Matthew 
Published: January 2020

Abstract

Background
Firmicute bacteria and the metabolites they produce are perturbed in ulcerative colitis (UC) patients. SER-287, an oral formulation of live Firmicute spores, was found to be safe and effective in achieving clinical remission in a Phase 1b clinical trial in mild-to-moderate UC. We assessed changes in the stool metabolome and host transcriptome among remitters and non-remitters as a measure of SER-287 pharmacodynamics.

Methods
58 UC subjects (modified Mayo score 4–10) were randomly assigned to one of four 8-week induction treatment arms preceded by a 6-day antibiotic preconditioning phase as follows: a) placebo/placebo b) placebo/SER-287 weekly c) vancomycin/SER-287 weekly or d) vancomycin/SER-287 daily. Clinical remission was defined as a Total Modified Mayo Score ≤2 plus an endoscopic subscore ≤1. Stool samples were evaluated for microbiome composition (whole metagenomic sequencing), targeted and global metabolomics (liquid chromatography-mass spectrometry) and transcriptomics (RNA-Seq with mucosal biopsy) at baseline and at week 8.

Results
Vancomycin/SER-287 daily was associated with higher rates of clinical remission compared to placebo/SER-287 weekly, vancomycin/SER-287 weekly or placebo/placebo (40%, 13.3% 17.6% and 0%, respectively; p=0.024 for the comparison of daily SER-287 versus placebo/placebo). Significant changes in microbial-associated metabolites (bile acids, indole, taurine, and arachidonate) were associated with clinical outcome across all arms (p&lt;0.05, Mann-Whitney; Figure A). Similar associations with treatment were also observed (p&lt;0.05, Mann-Whitney). Host transcriptomic changes associated with clinical outcome across arms included decreased expression of genes associated with signaling of TNF, NF-kappaB and IL-17, as well as increased expression of genes associated with the metabolism of the short chain fatty acid propanoate (adjusted p-value&lt;0.05, gene set enrichment analysis, GSEA; Figure B). Similar associations with treatment were also observed (adjusted p-value&lt;0.05, GSEA).

Conclusions
In this Phase 1b study of SER-287 the highest rates of remission were associated with daily dosing of SER-287, preceded by vancomycin preconditioning. Across treatment arms, clinical remission was associated with a wide range of metabolomic and transcriptomic changes relevant to UC pathogenesis. Changes in metabolomics and transcriptomics are associated with immune cell recruitment and activation, epithelial integrity and mucosal barrier function, giving insights into the mechanism of action of this microbiome therapeutic.
P165 INFLUENCE OF THE GUT MICROBIOTA ON COLONIC HISTONE MODIFICATIONS THROUGH BUTYRATE METABOLISM UNDER HEALTHY AND INFLAMMATORY CONDITIONS
Authors: Lund Peder , Smith Sarah , Simithy Johayra , Chau Lillian , Friedman Elliot , Saiman Yedidya , Gates Leah , Leboeuf Marylene , Trefely Sophie , Lopes Mariana , Yuan Zuo-Fei , Janssen Kevin , Kim Min-Soo , Petucci Christopher , Snyder Nathaniel , Bewtra Meena , Allis C David , Wu Gary , Garcia Benjamin 
Published: January 2020

Abstract
Inflammatory bowel disease (IBD) is often associated with a disruption in the composition and activity of the gut microbiota, referred to as dysbiosis. Since the microbiota has the potential to interact with host epithelial cells through small molecules generated from microbial metabolism, knowledge of how inflammation alters the microbial metabolome and how epithelial cells react is important for a better understanding of how IBD develops and persists. Butyrate, a short chain fatty acid produced through fermentation of dietary polysaccharides, has long been known to inhibit histone deacetylases (HDACs), which represent one of the many types of enzymes responsible for the epigenetic control of gene expression through the post-translational modification of histone proteins. We and others have observed that colonic epithelial cells from germ-free mice have reduced levels of acetylation on histone H4, which appears to be distributed throughout the genome based on sequencing analysis. The decreased levels of H4 acetylation may stem from a lack of butyrate, and therefore uninhibited HDAC activity, in germ-free mice. However, since colonic epithelial cells utilize short chain fatty acids as an energy source, an alternative explanation is that the germ-free condition results in less oxidation of butyrate to acetyl-CoA, which is the donor substrate for histone acetylation reactions. Isotope tracing experiments, in which cultured cells were incubated with labeled butyrate, demonstrated that the acetyl groups of histones contained carbon derived from butyrate. We have also performed isotope tracing experiments in mice using labeled inulin, a plant polysaccharide that presumably undergoes fermentation into short chain fatty acids. In this more physiologically relevant model, we detected isotope incorporation into the acetylated histones of colonic epithelial cells at rates of 5–20%, which appears dependent on the microbiota since labeling is sensitive to antibiotic treatment. To identify the metabolic pathways that link inulin to histone acetylation, we are investigating which metabolites become isotopically labeled using untargeted metabolomics. We will apply the same approach to the DSS-induced model of colitis to investigate how inflammation modulates the gut metabolome as well as the metabolic connections between the microbiota and the host. Our studies may uncover metabolic pathways that become dysregulated during inflammation, which may contribute to the pathogenesis of diseases such as IBD.
P012 HOSPITAL RE-ADMISSION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE – WHAT ARE THE RISK FACTORS?
Authors: Patel Rajan , Fromson Renate , Routledge Emma , Johnson Emma , Jameie-Oskooei Sina , Blad William , Moledina Saadiq , Wong Voishim 
Published: January 2020

Abstract

Introduction
Early re-admission after hospitalisation for an inflammatory bowel disease (IBD) flare is a negative quality indicator and causes unnecessary healthcare expense. Scoring systems to predict IBD readmissions have been shown to be ineffective. We aimed to describe the IBD re-admission rate at our hospital and investigate the risk factors.

Methods
Retrospective study of patients admitted to a London-based district general hospital under the gastroenterology team with a flare of inflammatory bowel disease between 2015 and 2018. Characteristic including but not limited to demographics, disease type, length of stay during index admission, biochemistry and biologic use were recorded. Hospital software (Sunquest Integrated Clinical Environment, Medway) was used to identify patients re-admitted at 30 and 90 days after discharge. Multivariate logistic regression was performed.

Results
138 patients were admitted with an IBD flare during the study period (74 (53.6%) Crohn’s disease (CD), 56 (40.6%) ulcerative colitis (UC), 8 (5.8%) IBD-U). Median age 33.5 (IQR 26 – 52), 71 (51.4%) female. Median length of stay was 4.5 days (IQR 1.8 – 8). 36 (26%) patients were taking a biologic.
Re-admissions occurred within 30 days in 19 patients (13.7%) and within 90 days in 30 patients (21.7%).
Multivariate logistic regression showed that a raised CRP on discharge was associated with re-admission. For every increased unit of CRP by one there was an increased risk of readmission by 1.1 times (p=0.05). Patients aged 22–39 were significantly less likely to be readmitted (OR: 0.38, p=0.015). Male patients were significantly more likely to be readmitted (OR: 2.52, p=0.05).

Conclusion
The 30 day and 90 day re-admission rate for our IBD population is just over 10% and 20%, respectively. CRP at discharge is significantly associated with both 30 and 90 day re-admission. After adjusting for confounders; CRP, age older than 40 and male gender were associated with re-admission to hospital. We advise caution in discharging IBD patients with raised inflammatory markers. Close follow up within a few days of discharge would be appropriate in this high risk sub-group.
P003 INFLAMMATORY BOWEL DISEASE PATIENTS’ PERSPECTIVES OF CLINICAL TRIALS
Authors: Rubin David , Peyrin-Biroulet Laurent , Reinisch Walter , Tole Swati , Sullivan Laura , Park K T , Regueiro Miguel 
Published: January 2020

Abstract

Background
Despite recent progress in treatment for inflammatory bowel diseases (IBD), there is a need for therapies with long-term efficacy and improved safety. Clinical trials in IBD face challenges with patient recruitment because of study designs, competitive or overlapping trials, and a limited number of eligible patients. We sought to better understand patients’ motivations, awareness of, and experience with IBD clinical trials.

Methods
We conducted an international survey of adult patients with IBD consisting of 2 components. The quantitative component, a 15-minute online survey, was completed by all patients. A qualitative component, a 30-minute telephone interview, was completed by a subset of patients from the United States (US). All percentages indicate results from the online survey.

Results
226 patients (mean age, 41.9 y) completed the online survey. Survey respondents included patients with ulcerative colitis (52%) and Crohn’s disease (48%) from the US (n=100, 21 of whom underwent a phone interview), Brazil (n=26), Canada (n=25), France (n=25), Germany (n=25), and Spain (n=25). Ninety-six percent of respondents reported at least a basic understanding of clinical trials, and 34 (15%) were current or past clinical trial participants.
Patients reported learning about trials through 1 or more sources (could select as many as applied): health care providers (42%), pharmaceutical manufacturer websites (31%), social media (30%), online support groups (28%), and foundations (18%-23%). In the survey, patients rated conversations with health care providers most helpful, but patients who were interviewed revealed that most physicians often do not initiate conversations about clinical trials, and patients typically do not ask.
Primary motivators for trial participation (rated from “does not encourage me at all” to “encourages me very much”) included altruistic goals of advancing medicine (67%), potentially mitigating risks of uncontrolled IBD such as colon cancer (59%), and access to treatment options that could improve quality of life (59%) or would otherwise be unaffordable (52%). Major barriers to participation (rated from “does not discourage me at all” to “discourages me very much”) included invasive screening and monitoring (35%), concern over receiving placebo (35%), or suboptimal treatment (33%), and concerns about posttrial access to study medication (27%). The majority (68%) reported that being in a clinical trial means being a “guinea pig” for an experimental treatment.

Conclusion
Opportunities to improve patients’ clinical trial experience in IBD include better communication with health care providers and improved patient education about clinical trial design and ethics. Ultimately, a better understanding of the patient perspective will be important for more informed patients and potentially higher recruitment and enrollment.
P021 READABILITY AND QUALITY OF ONLINE RESOURCES ON NUTRITION AS IT RELATES TO IBD
Authors: Khan Ali , Baumgartner Scott , Rao Vinay , Borum Marie 
Published: January 2020

Abstract

Background
Nutrition plays an essential role in inflammatory bowel disease (IBD). Optimizing nutritional status can help prevent malnutrition, osteoporosis, and may be an effective primary therapy for many patients. Patients with IBD are increasingly turning to the Internet for information. This study evaluated the readability and quality of online resources discussing nutrition for IBD.

Methods
Google search engine was used to query “nutrition and inflammatory bowel disease” to access the first 100 websites. Websites that were non-accessible, duplicates, videos without transcripts or evaluated animal models were excluded. Websites were categorized as informational or academic/professional. Readability was determined using the validated Flesch-Kincaid Grade Level Calculation. The quality of the information was determined using the validated DISCERN score. Websites were reviewed for inclusion of a discussion of shared decision making between patients and physicians. Statistical analysis was performed using a two-tailed Fisher’s Exact Test and a two-sample T-test with a significance value set at p &lt;0.05.

Results
89 of 100 websites met the inclusion criteria. 50 (56.2%) websites were informational and 39 (43.8%) were academic. The average Flesch-Kincaid Grade level was 13.2, with no significant difference between informational and academic websites (13.1 and 13.4 grade levels, respectively; p=0.760). The average DISCERN score was “good” without significant difference between informational and academic websites (45.75 and 45.74, respectively; p=0.994).
Academic websites had significantly more “excellent” DISCERN scores than informational websites (76% and 24%, respectively; p = 0.0054). There were no significant difference in “good” or “poor” DISCERN scores between academic and informational websites (p=0.527 and p=0.095, respectively) (Figure 1). Shared decision making between patient and physician was discussed among 33.7% of all sources, significantly more often among informational than academic sources (60% and 0%, respectively; p=0.0001).

Discussion
Patients often self-manage their symptoms using easily accessible online resources. While our study demonstrated near identical DISCERN scores between academic and informational websites, the average Flesch-Kincaid Grade Level exceeded the NIH recommended 6th grade reading level. Informational websites, however, were more likely to encourage shared decision making between physician and patient. It may be important for academic online resources to specifically emphasize communication that encourages shared decision making between IBD patients and physicians. As the use of online resources continues to increase, further efforts should focus on developing informational resources written at a grade level which is applicable to the general public.
P022 SHIFTING COST-DRIVERS OF HEALTH CARE EXPENDITURES IN INFLAMMATORY BOWEL DISEASE
Authors: Click Benjamin , Lopez Rocio , Arrigain Susana , Schold Jesse , Regueiro Miguel , Rizk Maged 
Published: January 2020

Abstract

Background
Inflammatory bowel diseases (IBD) are costly, chronic illnesses. Key cost-drivers of IBD healthcare expenditures include pharmaceuticals and unplanned care, but evolving treatment approaches have shifted these factors. We aimed to assess changes in cost of care, determine shifts in IBD cost-drivers, and examine differences by socioeconomic and insurance status over time.

Methods
The Medical Expenditure Panel Survey (MEPS), a nationally representative database that collects data on healthcare utilization and expenditures from a nationally representative sample since 1998 was utilized. Adult subjects with IBD were identified by ICD-9 codes. In order to determine changes in per-patient costs or cost-drivers unique to IBD, a control population of rheumatoid arthritis (RA) subjects was generated and matched in 1:1 case to control. Total annual healthcare expenditures were obtained and categorized as outpatient, inpatient, emergency, or pharmacy related. Temporal cohorts from 1998 to 2015 were created to assess change over time. Per-patient expenditures were compared by disease state and temporal cohort using weighted generalized linear models.

Results
Total of 641 IBD subjects were identified and matched to 641 RA individuals. From 1998 to 2015, median total annual healthcare expenditures nearly doubled (adjusted estimate 2.20; 95% CI 1.6–3.0) and were 36% higher in IBD compared to RA. In IBD, pharmacy expenses increased 7% to become the largest cost driver (44% total expenditures). Concurrently, inpatient spending in IBD decreased by 40%. There were no significant differences in the rate of change of cost-drivers in IBD compared to RA.

Conclusions
Per-patient healthcare costs for chronic inflammatory conditions have nearly doubled over the last 20 years. Increases in pharmaceutical spending in IBD may be accompanied by reduction in inpatient care. Additional studies are need to explore patient, disease, system, and industry level cost mitigation strategies.
P030 WHAT ABOUT DEPRESSION? INCREASED DISCUSSION BY GASTROENTEROLOGISTS MAY BE NEEDED.
Authors: Negreira Katherine , Gibilisco Jessica , Rao Vinay , Dave Jenny , Borum Marie 
Published: January 2020

Abstract

Introduction
Studies have reported an increased prevalence of depression in patients with inflammatory bowel disease (IBD). Depression rates have been reported as high as 21.2% in IBD patients compared to 13.4% in healthy controls (1). Addressing depression and improvement in psychological health has been associated with decrease in IBD-related morbidity, reduction in health-care utilization and improvement in quality of life (2). This study evaluated the rate at which gastroenterology providers discussed or documented depression and /or anxiety in IBD patients.

Methods
A 5-year chart review of all IBD patients seen in a university GI clinic was conducted. A confidential database using Microsoft Excel included patient age, gender, race, disease type, depression or anxiety (in GI notes or remainder of electronic medical record) was created. Statistical analysis using Fisher’s Exact Test was performed with significance set at p&lt;0.05. The study was approved by the institutional IRB.

Results
381 records of IBD patients were reviewed. There were 209 females and 172 males (mean age 44 years; range 20–82). 96 had Crohn’s disease, 279 had Ulcerative Colitis, and 6 had indeterminate colitis. Self-reported race/ethnicity included 195 White, 97 African American (AA), 11 Asian, 1 Hawaiian, 34 other and 43 did not document an ethnicity. 66 (17.32%) patients had depression and/or anxiety, 298 (78.22%) did not have depression and/or anxiety and 17 (4.46%) patients did not have documentation of mental health discussion during appointments. In patients with depression and/or anxiety, 46.97% had it documented by a gastroenterology provider. There was no statistically significant difference of depression and / or anxiety based upon gender (p=1.000), ethnicity (White vs AA p=1.000; White vs Asian p=0.2129; Asian vs AA p=0.208) or disease type (p=0.091).

Conclusion
Depression is reported to occur more frequently in patients with IBD compared to the general population. However, this study revealed that university gastroenterology providers did not consistently document the presence of or a discussion about depression and/or anxiety. While this study is limited based upon size and single institution design, it suggests that increased attention to psychological health is needed in IBD patients to optimize health and clinical outcomes.

References
P038 ASSESSING THE ASSOCIATION BETWEEN ACTIVE IBD AND DEPRESSION/ANXIETY USING ADAPTIVE TESTING TECHNOLOGY
Authors: Karpin Jordan , Rodriguez Tina , Traboulsi Cindy , Rai Victoria , Rubin David 
Published: January 2020

Abstract

Introduction
Both depression and anxiety are comorbidities of inflammatory bowel disease (IBD). Though previous studies have proposed a relationship between depression, anxiety and IBD, causality and directionality are unknown. We used a novel computerized adaptive testing technology to screen IBD patients for depression and anxiety and compared the screening results to disease activity.

Methods
Consecutive patients at our tertiary IBD clinic were asked to complete the validated CAT-MH™ survey (Adaptive Testing Technologies, Chicago, IL); we then reviewed disease and patient characteristics. Clinical remission status was determined by the senior author, blinded to the CAT-MH results. Simple statistics were performed.

Results
100 patients (57 women, 81 Caucasian, 63 Crohn’s disease) participated in the study, 58 of whom had no previous history of psychiatric disorders. We identified 42 patients with depression (40 mild, 2 moderate). Of those with mild depression, 25/40 (62.5%) were previously undiagnosed; of those with moderate depression, 1/2 (50%) were previously undiagnosed. 27 subjects tested positive for anxiety (21 mild, 6 moderate). 11/21 (52.38%) of mild anxiety cases and 3/6 (50%) of moderate anxiety cases were previously undiagnosed. 1 of the 100 patients was positive for suicidal ideation in the past month. Sex, race, type of IBD, smoking status, IBD-related surgical history, and number of discontinued medications were not statistically significant factors in depression or anxiety by proportion of patients or severity score. Clinically active disease status was found to be positively associated with depression severity score (p=0.002, 95% CI 4.3–19.5) and anxiety severity score (p=0.019, 95% CI 1.4–16.0) (Table 1). Of the 30 patients who had clinically active disease, 18 (60%) were positive for depression and 12 (40%) were positive for anxiety. Of the 70 patients in clinical remission, 24 (34%) were positive for depression and 15 (21%) were positive for anxiety (Figure 1). Patients with active disease have a significantly greater relative risk for having depression (RR 1.8, 95% CI 1.1–2.7) and an almost significantly greater relative risk of having anxiety (RR 1.9, 95% CI 0.99–3.5).

Conclusions
Using a novel screening tool for depression and anxiety in IBD patients, we identified a positive correlation between clinically active disease status and the presence of depression and anxiety. Our results show that regardless of past surgical and therapeutic IBD history, patients in clinical remission are less likely to have these mental health conditions than those with active disease. Gastroenterologists should consider patients with clinically active disease at higher risk for psychological co-morbidities, and include such screening in their routine care. Further research will explore directionality between disease activity and psychological outcomes.