bluuebunny/crossref_metadata_2025_split huggingface dataset:
659 Epidemiology of Major Depressive Disorder, Anxiety Disorder, and Bipolar Disorder in Crohn's Disease in the United States Between 2014 and 2019: A Population-Based National Study
Authors: Chouhan Vijit , Mansoor Emad , Saleh Mohannad Abou , Katz Jeffry , Regueiro Miguel , Cooper Gregory S. 
Published: October 2019

INTRODUCTION:
Studies have shown that patients with Crohn's disease (CD) are at an increased risk for developing various psychiatric illnesses including depression, anxiety, and bipolar disorder. However, these studies have been limited by a small sample size. We aimed to describe the epidemiology of psychiatric illness in CD through utilization of a large sample population.

METHODS:
We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record data from 26 major integrated US healthcare systems. We identified an aggregated patient cohort of eligible patients with a diagnosis of CD and depression, anxiety, and bipolar disorder between 2013 and 2018 based on the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). We also identified patients with a diagnosis of depression, anxiety, or bipolar disorder without CD. We calculated the overall prevalence of depression, anxiety, and bipolar disorder in CD amongst various patient groups. We also performed univariate analyses to identify risk factors for psychiatric illness in CD.

RESULTS:
Of the total number of patients in the database with CD, 28,640 had depression, 38,640 had anxiety, and 11,410 had bipolar disorder, with prevalences of 19%, 25%, and 8%, respectively. Depression, anxiety, and bipolar disorder in CD were more prevalent than in individuals without CD. Within CD, psychiatric illness was more prevalent in elderly (age >65 years old), females, and Caucasians. Compared to patients with psychiatric illness without CD, patients with psychiatric illness and CD were more likely to have a history of alcohol abuse, tobacco use, substance use, personality disorder, and corticosteroid use.

CONCLUSION:
This is one of the largest studies to date to describe the epidemiology of psychiatric illness in CD. Individuals with CD were more likely to suffer from depression, anxiety, and bipolar disorder compared to their non-CD counterparts. Prevalence of psychiatric illness in CD was more common in elderly, females, and Caucasians. Psychiatric illness should be actively screened for and treated accordingly in CD.
663 Onset of Response With Infliximab vs. Vedolizumab in the Treatment of Bio-Naïve Inflammatory Bowel Disease
Authors: Fourment Chris , Ritter Timothy E. , Kuten Samantha A. , Hardin Thomas C. , Van Anglen Lucinda J. 
Published: October 2019

INTRODUCTION:
Both infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel disease (IBD) in adults. Compared to IFX, VDZ is thought to have a slower onset of response. The purpose of this study was to characterize the incidence and timing of clinical remission between IFX and VDZ.

METHODS:
We performed a retrospective cohort study of bio-naïve adult patients (pts) treated with IFX or VDZ for ulcerative colitis (UC) or Crohn's disease (CD) at a large multicenter gastroenterology private practice. Pts were case-matched 1:1 based on age, gender, diagnosis, and baseline disease severity using the partial Mayo (pMayo) for UC and the modified Harvey-Bradshaw Index (mHBI) for CD. Primary endpoints were clinical remission rates at 6 months (mos), defined as pMayo less than 2 or mHBI less than 5, and time to remission represented by a Kaplan Meier curve. Pts in remission at baseline and those discontinuing therapy <6 mos were excluded from analyses.

RESULTS:
A total of 77 IFX (58 UC, 19 CD) and 77 VDZ (58 UC, 19 CD) case-matched pairs were generated. Baseline demographics were similar between IFX and VDZ groups: mean age 45 ± 16.9 vs 46 ± 16.2, male gender 60% vs 61%. Thirty-three pts were excluded from efficacy analyses: 8 in remission at baseline, 25 discontinuing therapy < 6 mos (16 IFX, 11 VDZ). Data are presented for the remaining 121 pts: IFX 60 (47 UC, 13 CD) and VDZ 61 (48 UC, 13 CD). Disease severity scores over 6 mos are depicted in Figure 1, with both IFX and VDZ demonstrating a rapid response by 2 weeks of treatment. Remission rates were similar among IFX and VDZ-treated UC patients (78.7% vs 64.6%, P = 0.13), and significantly higher for IFX-treated CD patients (84.6% vs 46.2%, P = 0.04). There was no difference in time to remission (Figure 2).

CONCLUSION:
We observed rapid onset of response and high remission rates among bio-naïve pts treated with both IFX and VDZ. While IFX-treated CD patients experienced significantly higher remission rates, our numbers were small. Importantly, time to remission did not differ between IFX and VDZ-treated pts. These data need to be verified in a larger cohort.
664 Relapse Rate From Deep Remission After Withdrawal of Anti-TNFa in Inflammatory Bowel Disease: A Meta-Analysis
Authors: Gulati Alakh , Alipour Omeed , Shao Ling , Zhang Bing 
Published: October 2019

INTRODUCTION:
Clinical remission has traditionally been the therapeutic target in the treatment of inflammatory bowel disease (IBD). However, emerging paradigms suggest deep remission (DR), often defined as clinical remission and mucosal healing with or without additional criteria, as a goal of therapy. Literature suggests longer intervals to relapse after withdrawing anti-TNFα therapy in DR, compared to clinical remission, in patients with IBD. This meta-analysis aims to determine the rates of relapse following anti-TNFa withdrawal in patients with DR.

METHODS:
Using search terms (“inflammatory bowel diseases” OR “IBD” OR “crohn*” OR “ulcerative colitis” OR “UC” OR “colitis”) AND (“mucosal healing” OR “deep remission” OR “complete remission” OR “full remission” OR “endoscopic remission”), 7,514 studies were identified from Pubmed and EMBASE on Oct 1, 2018. Inclusion criteria were adult IBD patients achieving DR with anti-TNFα treatment, defined as clinical remission and mucosal healing, who were followed to assess for relapse, defined as clinical or endoscopic disease activity. Studies with pediatric patients, patients maintained on steroids, and non-English publications were excluded. Publications were reviewed for inclusion independently by two authors; a third served as tie-breaker. Statistics was performed with OpenMetaAnalyst.

RESULTS:
Four manuscripts and one abstract with 234 cases at 1-year and 104 cases at 2-years were included. Anti-TNFα agents used were infliximab or adalimumab in all studies. All patients were withdrawn from anti-TNFα after achieving DR, some were continued on salicylate or immunomodulators. Within one year of withdrawal, 28.3% (67/234; I2 = 54.64%, P = 0.066) of patients demonstrated relapse from DR. Within two years, 47% (49/104; I2 = 0%, P = 0.721)) relapsed. No predictors of relapse from DR were reported.

CONCLUSION:
Literature describes the 1-year and 2-year relapse rate after anti-TNFα withdrawal from patients who achieved clinical remission to be approximately 40% and 60%, respectively. We found 1-year and 2-year relapse from DR after anti-TNFα withdrawal to be 28.3% and 47%. While the rates of relapse from DR are greatly reduced compared to relapse from clinical remission, nearly half of patients still experience relapse within two years after stopping anti-TNFα. This highlights the need for patient-physician discussion on significant relapse risk prior to stopping anti-TNFα therapy despite achievement of deep remission.
666 Outcomes Following Therapeutic Drug Monitoring of Vedolizumab
Authors: Graziano Elliot J. , Gheysens Katherine , Cross Raymond K. , Campbell James , Vaughn Byron 
Published: October 2019

INTRODUCTION:
Therapeutic drug monitoring (TDM) of biologic therapies is increasingly used in the management of inflammatory bowel disease (IBD). It is established that for anti-tumor necrosis factor medications, a dose escalation will have a positive clinical response in up to 86% of those with low serum drug concentrations. However, it is unknown if trough concentration predicts response to VDZ dose escalation. The objective of this study was to evaluate the impact of TDM on clinical outcomes in patients with IBD treated with VDZ.

METHODS:
This was a retrospective study of patients with IBD treated at two institutions (University of Minnesota, University of Maryland) with VDZ who had a VDZ trough concentration post induction between November 2016 and October 2018. A positive response was defined as improvement in the factor that was the etiology of dose escalation and categorized as clinical response, biomarker (i.e., CRP) response, or endoscopic response. An a priori VDZ trough concentration of 10 ug/ml was chosen as the cut off for a low level. Data was collected including demographics, disease characteristics, management changes and outcomes. VDZ concentration was performed using a commercial test (Inform Diagnostics, Irving, TX). Student's t-test and Fisher's exact test were used for continuous and categorical variables respectively in JMP Pro 14.0.0.

RESULTS:
48 trough concentrations were obtained in 43 patients. 51.2% had Crohn's disease while 48.8% had ulcerative colitis/indeterminate colitis. Following TDM, 62.5% (30/48) of patients underwent a dose change: 23 dose escalations, 5 stoppages and 2 dose de-escalations. 65% (13/20) of dose escalations (3 had inadequate follow-up) had a positive response to dose adjustment: 8 symptomatic response, 1 biologic response and 4 endoscopic response. Among those with a low VDZ trough <10 ug/ml, 75% (9/12) improved following dose escalations versus 50% (4/8) of those with VDZ trough ≥10 ug/ml (P = 0.356). The mean CRP prior to dose escalation was 7.0 mg/L (SD = 10.2) compared to 6.4 mg/L post dose escalation (SD = 12.3) (P = 0.863).

CONCLUSION:
TDM in VDZ results in frequent clinical management changes. While there was a greater percentage of patients that demonstrated clinical improvement following dose escalation with low drug levels, the difference was not statistically significant. Larger cohorts are needed to evaluate the impact of TDM with VDZ as our study was underpowered to identify small to moderate differences based on the pre-determined low VDZ level.
669 Increased Prevalence of Sinusitis Among Patients With Inflammatory Bowel Disease
Authors: Rai Victoria , Rubin David T. 
Published: October 2019

INTRODUCTION:
Sinusitis is characterized by inflammation of sinus tissue by infectious or noninfectious agents. The pathophysiology of sinusitis involves a combination of an inflammatory response by the nasal mucosa and, in some cases, excess bacteria growth. Though it is thought that similar dysfunction of the epithelial barrier in the gut with inflammatory bowel disease (IBD) occurs in the nasal passage with sinusitis, there has not yet been an established association between the two, and there are limited data describing the relationship between IBD and acute or chronic maxillofacial sinus inflammation or infection.

METHODS:
This is a retrospective study at our tertiary IBD center. We used our institution's anonymized electronic medical record data warehouse to identify patients with diagnostic codes for both sinusitis (J32) and IBD (K50.90 and K51.90), and recorded directionality of diagnoses and medication exposures. Patients with a confirmed diagnosis of IBD between January 2000 and May 2019 and age ≥18 years were included. Demographic and disease related information were collected. Categorical variables were analyzed using Fisher's exact test and continuous variables were analyzed using Wilcoxon rank sum test.

RESULTS:
The data warehouse includes 2.4 million patients in the time period defined, of which 14379 have IBD. There were 13446 non-IBD patients with a diagnostic code for sinusitis (0.56%), and 387 IBD patients with a code for sinusitis (2.69%; OR 4.8, 95% CI 4.3-5.3). We did not identify directionality in sinusitis diagnosis in IBD. Univariate analysis is reported in Table 1. Among the IBD patients, multivariate analysis adjusting for age of IBD diagnosis, sex, and race identified female gender (OR 1.47, 95% CI 1.19-1.83), black/African-American race (OR 3.75, 95% CI 1.55-12.34), history of bowel obstruction (OR 1.68, 95% CI 1.28-2.18), and past or current use of steroids (OR 2.51, 95% CI 1.99-3.19) as risk factors for having sinusitis in IBD. No significant differences were observed in average age at IBD diagnosis, smoking status, other immune medications or IBD type (Crohn's disease or ulcerative colitis).

CONCLUSION:
In our tertiary center, IBD patients had nearly 5-fold greater odds of sinusitis than non-IBD patients. Female gender, black/African-American race, bowel obstruction, and steroid use was associated with a diagnosis of sinusitis associated with IBD. Additional evaluation of these risk factors and potential screening and prevention strategies are warranted.
670 Development of a Novel Web-Based Yoga, Breathing, and Meditation Site for Patients With Inflammatory Bowel Disease
Authors: Rai Victoria , Lanson Biana G. , Rubin David T. 
Published: October 2019

INTRODUCTION:
Multiple studies have demonstrated that patients practicing yoga-based interventions/techniques have decreased anxiety and depression, increased self-efficacy and improved quality of life. This has included prior work with inflammatory bowel disease (IBD) patients. We developed novel videos and an educational website about yoga and breathing techniques which allows patients to perform these exercises on their own.

METHODS:
We worked with a certified yoga instructor and professional film crew to develop an online set of yoga, breathing and meditation exercises for those with digestive illnesses (IBDyoga.com) (Figure 1). The exercises are embedded in a non-profit foundation website and also available YouTube since Sept 2017. The website was promoted directly to patients in clinic, through group educational seminars and via social media. The site also features a voluntary survey regarding yoga and IBD. We report the outcome of these efforts.

RESULTS:
From Sept 2017 to June 2019, the Yoga Active Practice, Yoga Restorative Practice, and Breathing Exercises videos posted to YouTube received 4957, 1298, and 614 views respectively with mean view duration 9:25 min, 5:26 min, and 1:37 min, respectively. IBDyoga.com received 1900 unique pageviews with 692 returning users and a mean time on page of 2 min. 26 visitors completed our survey, 30% of whom were in self-described clinical remission from IBD and 70% with active IBD symptoms. 27% reported that they were new to yoga/meditation, 27% reported that they tried yoga/meditation techniques in the past, and 46% were experienced in these techniques. 81% of new to yoga/breathing/meditation reported as IBD symptomatic. 59% of total responders reported more energy, 77% reported better mood, and 67% reported less anxiety, while in symptomatic responders, 71% reported more energy and better mood, and 69% reported less anxiety. There were not significant differences between symptomatic and non-symptomatic visitors to IBDyoga.com with IBD.

CONCLUSION:
These novel yoga, meditation and breathing videos and resources for patients with chronic illness have attracted over 8900 views in the past 20 months. At IBDyoga.com, most of the users reported active IBD symptoms, and of those who completed the exercises, most reported having more energy, better mood and less anxiety. Additional work to promote this resource and study its potential benefits is ongoing.
674 Faster Sedation Times for Inflammatory Bowel Disease (IBD) Patients Undergoing Elective Endoscopic Procedures Can Be Safely Achieved With a Higher Propofol Induction Dosage Compared to Non-IBD Patients
Authors: Zhang Daniel S. , Stana Roman , Abraham Bincy 
Published: October 2019

INTRODUCTION:
Patients with inflammatory bowel disease (IBD) frequently undergo endoscopic procedures for diagnosis and management of disease activity. We have shown in a prior study that our IBD patient population have higher sedation requirements, which is consistent with other studies.1–3 However, there is limited data on induction dosing requirements comparing the IBD patient population to the non-IBD population. Here we conducted a retrospective study comparing the induction propofol dose and sedation time required for IBD patients compared to non IBD patients.

METHODS:
Patients 18 years or older undergoing elective outpatient endoscopy with an American Society of Anesthesiologists (ASA) score of 2 or less using total intravenous anesthesia (TIVA) from one designated anesthesiologist was included in the study. Adverse events were recorded. Age, body mass index (BMI), relevant comorbidities, medications, and endoscopic disease activity scores were recorded. The primary outcome was induction dose, which was defined as the amount of propofol per kilogram required to adequately and safely anesthetize a patient for the procedure as determined by the anesthesiologist. The secondary endpoint was the time to sedation. We used one anesthesiologist to reduce any variations in delivering anesthesia. The sample size needed for the primary outcome with 80% power and an alpha 0.05 was 88 total patients based on a mean difference of 0.5 mg/kg propofol induction dose.

RESULTS:
A total of 152 patients undergoing elective outpatient endoscopies met inclusion criteria, with 108 patients in the IBD arm and 44 patients in the non-IBD arm. Baseline characteristics were similar except for lower BMI 25.7 in the IBD group vs 29.1 kg/m2 in non-IBD group (Table 1). Baseline characteristics of the IBD group are shown in Table 2. Propofol induction dose was greater in the IBD group 3.42 ± 0.39 mg/kg compared to the non-IBD group 1.79 ± 0.17 seconds (P < 0.05) (Table 3). Sedation time was lower in the IBD group 38.9 ± 2.1 seconds when compared to the non-IBD group 88.5 ± 8.8 seconds (P < 0.05). No adverse events were reported in either group.

CONCLUSION:
Induction propofol dosage was significantly greater and sedation times were significantly faster in the IBD group compared to the non IBD group. Further studies are needed to understand the mechanism of propofol in contributing to anesthesia in the setting of inflammatory diseases compared to the general population.
682 Investigating the Pathogenesis of Ulcerative Colitis Through Meta-Analysis of Gene Expression Omnibus Data
Authors: Khorfan Kamal , Aljabban Jihad , Gurakar Merve , Khan Hajra , Aljabban Nabeal , Mukhtar Mohamad , Hadley Dexter 
Published: October 2019

INTRODUCTION:
Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the colon and rectum, alongside extra-colonic manifestations. The etiology is unclear but is thought to include such factors as genetic predisposition, immune regulation, microbiome, and environmental triggers. Though strides have been made in treatment, the failure of anti-IL13 drugs demonstrates our limited knowledge of UC pathology. Here we use meta-analysis to dissect UC pathogenesis.

METHODS:
We employed our STARGEO platform to search Gene Expression Omnibus and performed meta-analysis on 465 colon samples from active UC patients, using 326 healthy colon samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis.

RESULTS:
Our analysis identified granulocyte adhesion and diapedesis, TREM1 signaling, and communication between innate and adaptive immune cells as top canonical pathways. TNF, IFNγ, and IL1 were top upstream regulators with predicted activation. We noted upregulation of the DUOX/DUOXA2 enzyme system, responsible for generating reactive oxygen species. We also found upregulation of calprotectin S100A8, which defines UC severity, and downregulation of the E3 ubiquitin ligase RNF5 responsible for controlling S100A8 expression. Impaired epithelial integrity was suggested by upregulation of matrix metalloproteinases MMP1 and MMP3 and down regulation of claudin 8. Furthermore, downregulation of aquaporin 8 and guanylin suggests loss of absorption. Upregulation of the amino acid transporter SLC6A14 and aldolase B may represent a compensation for loss of absorptive function. We also found metabolic dysfunction through downregulation of phosphoenolpyruvate carboxykinase 1, and UDP-glucuronosyltransferases UGT1A7/A5/A3. Lastly, we found downregulation of several miRNAs including mir-188, 192, 200a/b, 215, and 320.

CONCLUSION:
UC pathogenesis represents a multifactorial disease process that remains elusive. Here we suggest several mechanisms that may underpin UC development and susceptibility. In a recent study, inverse expression of RNF5 and S100A8 was found to coincide with UC severity and our results give credence to this correlation. Our results also demonstrate the parts that DUOX/DUOXA2 system and loss of epithelial and metabolic integrity have in UC. Lastly, miRNAs have an emerging role in UC and mimic therapy of the downregulated miRNAs we identified may prove efficacious. These results provide novel insights into UC pathophysiology and potential therapeutic avenues.
683 Audit of Introducing Fecal Bile Acid Diagnostic Test in Evaluation of Diarrhea in Patients With Inflammatory Bowel Disease in a Tertiary Care Center
Authors: Chedid Victor , Vijayvargiya Priya , Donato Leslie , Calderon Gerardo , Raffals Laura E. , Camilleri Michael 
Published: October 2019

INTRODUCTION:
Patients with inflammatory bowel disease (IBD), whether Crohn's disease (CD) or ulcerative colitis (UC), have known alterations in the enterohepatic circulation of bile acids (BA) that may contribute to chronic diarrhea, but the fecal BA patterns are not well defined. We aimed to audit all patients with IBD who had fecal BA measurements as part of evaluation of chronic diarrhea at a tertiary care center.

METHODS:
Methods: 65 patients with IBD (18 with UC and 47 with CD) were evaluated at a single center and underwent measurements of fecal total and individual BAs based on a 48-hour collection performed at the end of a 4-day, 100-gram fat diet. The electronic medical records were interrogated to obtain type of IBD, disease activity, location of disease, prior surgery, IBD related therapies, presenting symptoms, and response to treatment with BA sequestrants. Bile acid diarrhea (BAD) diagnosis was based on >10% primary BAs, >4% primary BAs + >1,000 µmol/48 h, or total fecal BAs >2,337 µmol/48 h. IBD disease activity was based on radiologic, endoscopic and histologic parameters. Data are reported as mean ± standard error of the mean (SEM).

RESULTS:

Table 1 summarizes the patterns of BAD in our cohort with IBD. Figure 1 demonstrates the mean ± SEM of total fecal BAs and % primary BAs in each group of IBD patients. Among patients with UC, 10 had poorly controlled disease and 8 had well controlled disease, and both cohorts had elevated primary BAs (mean 28.9% ± 12.5%; 34.6% ± 21%, respectively). All patients with an ileal pouch anal anastomosis (IPAA) had elevated total fecal BAs (BADt) compared to those with an intact colon. In patients with CD, those with ileal resections had elevated BADt and % primary BAs (6263 µmol/48 h ± 1012 µmol/48 h; 79% ± 5.9%, respectively). Patients with an intact ileum, had elevated % primary BAs regardless of disease activity: controlled CD 34.7% ± 9.3%; poorly controlled CD 57.8% ± 9.5%; 15 out of 47 patients with CD were started on BA sequestrants with a positive response in 10/15.

CONCLUSION:
Discussion: BAs may play a role in the pathophysiology of chronic diarrhea in patients with IBD, regardless of inflammatory disease activity. Future studies are required to assess the impact of fecal bile acid testing and treatment with BA sequestrants on inflammation and chronic diarrhea in patients with IBD.