bluuebunny/crossref_metadata_2025 huggingface dataset:
624 Clinical Outcomes and Endoscopist's Perception of the Use of Hemospray for Gastrointestinal Bleeding: Outcomes From a U.S. Academic Tertiary Care Medical Center
Authors: Weaver Michael , Rood Richard P. , Mullady Daniel , Early Dayna
Published: October 2019

INTRODUCTION:

Endoscopic management of gastrointestinal bleeding (GIB) has evolved with current standard treatment modalities including epinephrine injection, hemostatic clips, and thermal therapies. A growing body of evidence has demonstrated clinical efficacy of Hemospray in GIB. Recently, the FDA approved Hemospray for treatment of non-variceal GIB in the USA.

METHODS:

Consecutive patients treated with Hemospray for management of GIB between 10/2018 and 1/2019 were included in this prospective case series. IRB approval was obtained. Patient demographics, clinical parameters, outcomes, and endoscopist's perceptions on the ease of use of Hemospray were collected. Hemospray was used by an attending as monotherapy, dual therapy with other standard endoscopic techniques, or as a rescue therapy.

RESULTS:

Hemospray was used during 12 cases for GIB. Immediate hemostasis was achieved in 10/12 (83.3%) cases with an average time to hemostasis of 3 minutes and an average of 6.8 sprays used per endoscopy. The mean Blatchford score was 13.7 and the mean Rockall score was 6.3. Hemospray failed in one case of failed band ligation and in one case as rescue therapy for a Forest Class 1a duodenal ulcer. Hemospray was used as a primary modality in 3/12 cases, adjunctive therapy in 3/12 cases, and as rescue therapy in 6/12 cases. Etiologies of GIB included Forest 1a ulcers (n = 3), Forest 1b ulcers (n = 3), MW tear (n = 2), GAVE (n = 1), APC induced rectal ulcer (n = 1), post polypectomy bleed (n = 1) and esophageal variceal bleed (n = 1). No adverse events occurred. Interventional radiology was utilized in 5/12 cases. The 3 day and 7 day rebleeding rates were 0% (0/12) and 25% (3/12) respectively. All-cause mortality was 8% (1/12) at both 7 and 30 days. Hemospray was technically easier to use compared to clips (6/12), epinephrine (4/12), and thermal modalities (5/12) according to the attending endoscopists (Table 1). Difficulties reported during administration of Hemospray included a clogged catheter (n = 2) which required use of a second catheter.

CONCLUSION:

Hemospray is effective in achieving immediate hemostasis in non-variceal GIB with no adverse events in our cohort. Low 3 and 7 day rebleeding rates were below the predicted rebleeding rates. Overall, a majority of attending endoscopists reported that Hemospray was similar or easier to use than conventional methods of hemostasis. Our study is limited by our small patient cohort, but represents real US experience with this recently FDA approved GIB treatment modality.
627 Carvedilol vs. Endoscopic Variceal Ligation in Primary Prevention of First Variceal Hemorrhage Episode: A Systematic Review and Meta-Analysis
Authors: Suchartlikitwong Sakolwan , Vutthikraivit Wasawat , Mingbunjerdsuk Thammasak , Zitun Mohamed , Tikue Alay M. , Nugent Kenneth
Published: October 2019

INTRODUCTION:

Either a non-selective beta blocker or endoscopic variceal ligation (EVL) is recommended for the primary prevention of a first variceal hemorrhage episode in patients with medium or large sized varices. Carvedilol has been used for this purpose because of its additional alpha-1 antagonist effect and fewer hemodynamic complications. However, data supporting this recommendation are based on two previous randomized controlled trials. More studies have been published since these trials to investigate the benefit of carvedilol. We wanted to compare carvedilol with EVL in patients with esophageal varices to prevent the first variceal hemorrhage episode and to reduce mortality.

METHODS:

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies were randomized controlled trials that investigated the efficacy of carvedilol compared to EVL to prevent the first variceal bleeding and to reduce mortality. The first variceal bleeding episode was defined as melena and/or hematemesis with endoscopic evidence of bleeding stigmata or recent variceal hemorrhage. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled risk ratio (RR) and 95% confidence intervals.

RESULTS:

Four randomized controlled trials from 2009 to 2018 involving 556 patients (276 patients in the carvedilol group and 280 patients in the EVL group) were included in this meta-analysis. The mean age was 50 years. Compared to EVL, carvedilol did not significantly decrease the first variceal bleeding incidence or 1-year mortality (pooled RR 1.11 (0.56-2.19), P = 0.767, I2 = 53% and 1.22 (0.78-1.91), P = 0.38, I2 = 0%, respectively) (Figures 1 and 2). Serious adverse events that were intolerable and required specific therapy leading to discontinuation of the treatment arm was reported in 4 studies and did not show any significant difference between the carvedilol group and the EVL group (pooled RR 1.14 (0.78-1.68), P = 0.49, I2 = 6.8%) (Figure 3).

CONCLUSION:

Our study demonstrated a non-significant difference between carvedilol and EVL to prevent first variceal bleeding or decrease mortality. There was no difference in serious side effects. More randomized controlled trials with larger sample sizes and long term follow up are required to better understand the potential benefit of carvedilol. Our analysis supports the benefit of carvedilol as primary prophylaxis of variceal hemorrhage in cirrhotic patients.
628 Proton Pump Inhibitors or Histamine-2 Receptor Antagonist Co-Therapy Decrease the Risk of Upper Gastrointestinal Bleeding in Patients on Direct Oral Anticoagulation: A Systematic Review and Meta-Analysis
Authors: Suchartlikitwong Sakolwan , Vutthikraivit Wasawat , Mingbunjerdsuk Thammasak , Zitun Mohamed , Laoveeravat Passisd , Shroff Roshan , Carrasco Cinthya , Nugent Kenneth
Published: October 2019

INTRODUCTION:

Direct oral anticoagulation (DOAC) has gained more universal acceptance for use in patients with venous thrombosis or atrial fibrillation because of its safety profile and the elimination of drug monitoring. However, upper gastrointestinal bleeding (UGIB) is a major complication, especially in those with higher bleeding risk. Recent studies have reported a decreased risk of UGIB in patients using DOAC with proton pump inhibitors (PPI) or histamine-2 receptor (H2RA) but the results are controversial. We aimed to assess the effect of PPI or H2RA co-therapy with DOAC on the risk of UGIB by a systematic review and meta-analysis.

METHODS:

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies were cohort (prospective or retrospective) studies that investigated the incidence of UGIB comparing between DOAC with and without PPI or H2RA co-therapy. Upper gastrointestinal bleeding is defined as melena or hematemesis that required hospitalization. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled risk ratio (RR) and 95% confidence intervals.

RESULTS:

Six studies from 2015 to 2018 were included in this meta-analysis and reported a total of 469,593 patients using DOAC. Mean age was more than 70 years. Proton pump inhibitors co-therapy and histamine-2 receptor antagonist co-therapy significantly decreased the incidence of UGIB in DOAC users (pooled RR 0.58 (0.45-0.74), P < 0.001, I2 = 0.0% and 0.63 (0.42-0.96), P = 0.033, I2 = 0.0% respectively) (Figure1 and 2). Three studies reported PPI plus H2RA co-therapy with DOAC decreased the incidence of UGIB but it is not statistically significance (pooled RR 0.71 (0.18-2.74), P = 0.616, I2 = 88.5%) (Figure 3).

CONCLUSION:

Our study demonstrated statistically significant benefit of the combination either PPI or H2RA co-therapy with DOAC to lower the incidence of UGIB. However, the combination of PPI and H2RA did not decrease the risk of bleeding. Randomized controlled trials studies are needed to further evaluate this association.
631 Cyanocrylate for Active Gastric Variceal Bleeding: Clinical Evolution
Authors: Wah-Suárez Martin I. , Cessa-Zanatta José C. , González-González José A. , Maldonado-Garza Héctor J.
Published: October 2019

INTRODUCTION:

Gastroesophageal variceal hemorrhage is an important complication from portal hypertension. Nearly 20% of this type of bleeding is from gastric varices (GVs), which is considered more profuse and severe compared to esophaeal variceal bleeding. There are many treatment modalities for GVs active bleeding. The use of tissue adhesives like cyanoacrylate is gaining acceptance for the treatment of GVs with a safe profile. The aim of this study is to determine the effectiveness of cyanoacrylate application in active GV bleeding.

METHODS:

We retrospectively reviewed the clinical data of 58 patients who underwent cyanoacrylate application in the setting of active GVs bleeding from January 2016 to July 2018. The outcomes of our study were initial hemostasis, inpatient bleeding, early rebleeding and 6-week mortality. The safety of the procedures was followed as well.

RESULTS:

A total of 75 procedures of cyanoacrylate injection were performed in 58 patients over a period of 3 years (January 2016-July 2018). Thirty-seven male patients (63.7%) with a mean age of 55.9 ± 13.8 years old were included. The mean duration of follow-up was 122 ± 2 days (range 1 to 719 days). From the total of patients enrolled, 32 (55.1%) and 11 (18.9%) were Child Pugh B and C, respectively. The main symptoms in these patients were hematemesis in 29 (50.0%), melena in 7 (12.0%), or both in 19 (32.7%). In the 58 patients evaluated, the different types of GVs were registered; many patients had more than one type of GVs according to Sarin´s classification. GV prevalence in our patients was GOV2 (43.1%), IGV1 (41.3%), GOV1 (22.4%) and IGV2 (10.3%). The success of the index endoscopic hemostatic procedure was 96.5%. A second endoscopy was performed in 58.6% of patients within 24 hours to assure complete blood vessel occlusion and no residual bleeding; a second cyanoacrylate injection was needed in 12% patients (20.6%). The inpatient and early rebleeding was 18.9% and 17.2%, respectively. The overall mortality was 18.9%. Adverse events were not detected in the current study.

CONCLUSION:

Cyanoacrylate injection is an effective therapeutic and safe option in acute GVs bleeding. We suggest an aggressive approach therapy in patients with active GVs bleeding, since it portends a higher incidence of recurrence; a second-look endoscopy, the use of endoscopic ultrasound and a thorough evaluation of rebleeding should be considered.
633 The Role of CHA2DS2-VASc Score vs. Anticoagulation for Predicting Morbidity and Mortality for Ischemic Bowel Disease Secondary to Atrial Fibrillation
Authors: Dasu Neethi R. , Khalid Yaser , McMahon Donald , Randle Troy
Published: October 2019

INTRODUCTION:

Atrial fibrillation is a common disorder with potentially multiple adverse outcomes, one such being ischemic bowel disease. The aims of this study are: to evaluate the role of CHA2DS2-VASc score as a predictor of higher mortality in patients who have atrial fibrillation and ischemic bowel disease, i.e., if a higher CHA2DS2-VASc score is associated with higher mortality; to evaluate whether being on anticoagulation is associated with a lower mortality for such patients in this population.

METHODS:

This retrospective study reviewed patients admitted to three community hospitals over a 3 year period with the primary diagnoses of atrial fibrillation and ischemic bowel disease. The subject cohort was gathered with ICD 10 codes. Baseline characteristics such as age, sex, CHA2DS2-VASc Score, mean Cr, and subjects use of anticoagulation were analyzed. Hazard ratios, P-values, Confidence Intervals, and a Cox proportional hazards model for the baseline characteristics were calculated. Kaplan-Meier curves were calculated and then plotted together for subjects on anticoagulation versus those not on anticoagulation. The area under the receiver operating characteristic (ROC) curve was employed to assess the predictive power of CHA2DS2-VASc score for mortality development among ischemic bowel disease patients with atrial fibrillation.

RESULTS:

Sixty-five patients were included. The majority of the patients were older than >75 (63%), female (69%), and had established HTN (68%). The mean CHA2DS2-VASc score was 4.25 with P-value <0.009. Utilizing the cox proportional-hazards model, the hazard ratios for females, patients with diabetes mellitus, and CHA2DS2-VASc score were statistically significant with P-value < 0.05 and hazard ratios with confidence intervals that did not include 1. The area under the curve of ROC was 0.67, indicating a fair-to-poor marker with regards to the predictive power of CHA2DS2-VASc score for mortality development in this patient population. When examining mortality in patients based on whether or not patients were on anticoagulation, the hazard ratio was 0.36 (CI 0.089) with P < 0.05. The Kaplan-Meier curves demonstrate longer survival and less mortality for patients with atrial fibrillation on anticoagulation.

CONCLUSION:

The predictive power of the CHA2DS2-VASc score was relatively low. The CHA2DS2-VASc score had a statistically significant hazard ratio, a score >4 had increased mortality. Patients on anticoagulation had less mortality than patients not on anticoagulation.
634 Transitioning From Vedolizumab IV to Vedolizumab SC in Patients With Ulcerative Colitis: Results From the VISIBLE Program
Authors: Wolf Douglas , Danese Silvio , Matthews Barbara , Jones Stephen , Chen Jingjing , Kisfalvi Krisztina , Sandborn William J.
Published: October 2019

INTRODUCTION:

Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is approved as an intravenous (IV) formulation to treat ulcerative colitis (UC). In the first completed study with a new VDZ subcutaneous (SC) formulation (VISIBLE 1, NCT02611830, a randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial assessing VDZ SC as maintenance treatment in adults with moderately to severely active UC), VDZ SC demonstrated statistically significant efficacy superior to placebo as maintenance treatment in patients with UC who had achieved a response to VDZ IV induction. The VDZ SC clinical program also includes an open-label extension (OLE, NCT02620046, ongoing). Analyses across these 2 studies allow for evaluation of efficacy when transitioning from VDZ IV to VDZ SC in patients who achieved clinical benefit with VDZ IV treatment for varying durations.

METHODS:

Efficacy of VDZ SC treatment after initial VDZ IV (300 mg) infusion was evaluated in 3 groups according to the duration of VDZ IV treatment before transitioning to VDZ SC (108 mg; Figure 1): (A) After 2 VDZ IV infusions (Week [W] 0 and 2) in patients who achieved clinical response at W6 and were randomized to VDZ SC maintenance treatment in VISIBLE 1; (B) After 3 VDZ IV infusions in patients who did not achieve clinical response at W6 who received a third VDZ IV infusion at W6 and had clinical response at W14 in VISIBLE 1 before enrolling in the OLE and transitioning to VDZ SC; (C) After 8 VDZ IV infusions (W0, W2, W6, and every 8 weeks thereafter until W52) in patients randomized to VDZ IV maintenance treatment in VISIBLE 1, completed 52 weeks of VDZ IV treatment, and transitioned to VDZ SC in the OLE.

RESULTS:

Patients who transitioned to VDZ SC after 2 infusions of VDZ IV (N = 106) had a clinical remission rate of 46.2% and a clinical response rate of 65.1% at W52. Among patients who received 3 VDZ IV infusions before transitioning to VDZ SC (N = 107), 39.2% achieved clinical remission and 48.0% achieved clinical response at W54 (14 weeks of IV; 40 weeks of SC). For patients who transitioned to VDZ SC after receiving 8 VDZ IV infusions over 52 weeks in VISIBLE 1 (N = 35), clinical remission and clinical response rates (both 76.9%) were maintained during the OLE on SC through W24 (Tables 1 and 2).

CONCLUSION:

Transitioning from initial VDZ IV treatment to VDZ SC maintenance treatment retains therapeutic benefit, independent of initial vedolizumab IV treatment duration.
638 Clinical Effectiveness of First-Line Anti-TNF Therapies and Second-Line Anti-TNF Therapy Post-Vedolizumab Discontinuation in Patients With Ulcerative Colitis or Crohn's Disease
Authors: Bressler Brian , Yarur Andres , Kopylov Uri , Bassel Marielle , Brett Neil R. , Lissoos Trevor , Lopez Claudia , Natsios Athanasios , Saha Sumit , Kifnidi Christina , Demuth Dirk , Patel Haridarshan , Mantzaris Gerassimos J.
Published: October 2019

INTRODUCTION:

Real-world data is needed to understand and compare the clinical effectiveness of second-line (2L) anti-tumour necrosis factors (anti-TNF) treatment (Tx) post first-line (1L; biologic-naive) vedolizumab (VDZ) and 1L anti-TNF use in patients (pts) with ulcerative colitis (UC) or Crohn's disease (CD).

METHODS:

This was a real-world, multi-country, multi-centre retrospective study in UC and CD pts (≥18 years old) treated with 1L anti-TNF or 2L anti-TNF after discontinuation of 1L VDZ for any reason (received May 2014-March 2018). Pts were from sites in Canada, Greece and the United States. Anti-TNF therapies included adalimumab, infliximab, golimumab and certolizumab pegol. The index date was defined as date of 1L Tx initiation. Clinical effectiveness data were collected from 1L or 2L Tx initiation to earliest of death, chart abstraction date. Cumulative rates of Tx persistence, clinical response and clinical remission were estimated using the Kaplan-Meier method for UC and CD (separately and combined) over 6 months. Clinical response and remission were assessed using pre-defined hierarchical algorithms of standard disease measures reported in the medical records. P-values were generated using the log-rank test.

RESULTS:

This analysis included 579 anti-TNF patients (1L: 497 [UC: 224; CD: 273]; 2L: 82 [UC: 58; CD: 24]) from 36 sites. Proportions of patients in each cohort were: adalimumab (1L: 41.4%; 2L: 19.5%), infliximab (1L: 52.7%; 2L: 79.3%), golimumab (1L: 4.8%; 2L: 1.2%) and certolizumab pegol (1L: 0.8%; 2L: 0.0%). Mean (SD) age at index date: 1L, 39.6 (15.2); 2L, 49.4 (18.6) years, male: 1L, 49.9%; 2L, 61.0%, median (range: min-max) disease duration: 1L, 2.0 (<0.1–49.0); 2L, 3.7 (0.1–54.0) years. At 6 months, cumulative rates of Tx persistence (1L: 83.9%; 2L: 83.6%), clinical response (1L: 49.5%; 2L: 65.6%) and clinical remission (1L: 29.5%; 2L: 31.4%), were similar between 1L and 2L patients (Table 1). Results were similar when data were stratified by UC and CD (Table 1), albeit sample sizes were small.

CONCLUSION:

Cumulative rates of Tx persistence, clinical response and clinical remission were comparable between 1L anti-TNF patients and those who switched to a 2L anti-TNF following the discontinuation of 1L VDZ. Results suggest that 1L VDZ may not impact the effectiveness of subsequent anti-TNF Tx in real-world clinical practice. As 2L sample size was limited, these hypothesis-generating data warrant further study.
639 A Multimodal Intervention Reduces Intravenous Opioid Exposure Among Hospitalized Patients With Inflammatory Bowel Disease
Authors: Dalal Rahul S. , Palchaudhuri Sonali , Snider Christopher , Gitelman Yevgeniy , Brahmbhatt Mihir , Mull Nikhil , Mehta Shivan , Klock Christopher , Lewis James , Lichtenstein Gary R.
Published: October 2019

INTRODUCTION:

Opioids (OPIs) are associated with increased mortality and infections in patients with IBD (AJG 2012;107(9):1409–22). Prior interventions targeting reductions in intravenous (IV) OPI exposure for all patients admitted to a general medical unit have decreased total OPI use without compromising pain control (JAMA IM 2018;178(6):759-63). We therefore performed a prospective evaluation of a multimodal intervention to reduce IV OPI exposure among IBD patients hospitalized at our institution.

METHODS:

This prospective study was conducted on a general medical unit at a large urban academic medical center from 1/1/19 to 5/31/19. Interventions to decrease IV OPI use were implemented in stages (Figure 1): 1. protocol for IV acetaminophen for IBD patients lacking enteral access 2. EHR “smartphrase” with analgesia guidance for use in gastroenterology consult notes 3. online IBD pain management pathway 4. automated text message alerts with analgesia guidance sent to providers. IV and total (IV+PO+TD) OPI exposures were measured in IV morphine mg equivalents (IVMME)/patient-day and compared to pre-intervention (1/1/18-12/31/18) data abstracted retrospectively from the EHR. IV acetaminophen and ketorolac use, length of stay (LOS), 30-day readmission rates (RRs), and pain scores (1-10 scale) were also assessed.

RESULTS:

Our study included 332 IBD patient encounters with similar baseline characteristics in pre-intervention (n = 241) and intervention (n = 91) periods (Table 1A). Between study periods, we observed a significant reduction in the proportion of patients receiving IV OPIs (43.6% vs. 30.1%, P = 0.03) and non-significant reductions in mean IV and total OPI exposures/patient-day (Table 1B). The proportion with highest OPI exposure (>39.0 IVMME/d, top quartile of non-zero total OPI exposure in 2018) was significantly reduced (13.7% vs. 5.5%, P = 0.04). Run charts were performed to correlate the timing of interventions to changes in OPI exposure (Fig 2). We observed appropriately increased IV acetaminophen use (0.8% vs. 14.3%, P < 0.01), similar mean pain scores (3.9 vs. 3.8, P = 0.74), non-significantly reduced IV ketorolac use (8.7% vs. 3.3%, P = 0.09), and significantly reduced mean LOS (7.2 vs. 5.2 d, P = 0.04) and 30-day RRs (21.6% vs. 11.0%, P = 0.03).

CONCLUSION:

A multimodal intervention successfully reduced IV OPI exposure for hospitalized IBD patients. This was associated with reduced LOS and 30-day RRs. Additional research is needed to determine long-term benefits of reduced OPI exposure in this population.
642 Effects of Ustekinumab Maintenance Therapy on Endoscopic Improvement and Histologic Improvement in the UNIFI Phase 3 Study in Ulcerative Colitis
Authors: Li Katherine , Friedman Joshua R. , Marano Colleen , Zhang Hongyan , Yang Feifei , Sandborn William J. , Sands Bruce E. , Feagan Brian G. , Peyrin-Biroulet Laurent , De Hertogh Gert
Published: October 2019

INTRODUCTION:

Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC), but its effects on mucosal healing (endoscopic improvement + histologic improvement) during maintenance treatment are unknown.

METHODS:

We evaluated the effects of maintenance UST on histologic and endoscopic activity in the UNIFI Phase 3 study of UST in moderate-to-severe UC (n = 961). Pts in response 8 weeks after receiving intravenous UST were randomized to receive maintenance treatment with subcutaneous (SC) placebo or UST 90 mg every 8 (q8w) or 12 weeks (q12w). Two colonic biopsies were collected from the distal colon at screening and Weeks 0 and 44 of maintenance. Endoscopic improvement (EI) was defined as a Mayo endoscopy subscore <1; histologic improvement (HI) comprised the following Geboes score-based criteria: absence of erosions or ulcerations, absence of crypt destruction, and <5% of crypts with neutrophil infiltration. To encompass both macro- and microscopic scales, histo-endoscopic mucosal healing (MH) was defined as achieving both EI and HI.

RESULTS:

At maintenance Week 44, EI was achieved in 28.6%, 43.6%, and 51.1% of pts treated with placebo, UST q12w (P = 0.002 vs placebo), and UST q8w (P < 0.001), respectively. HI was achieved at Week 44 in 32.9%, 54.0%, and 59.3% of pts treated with placebo, UST q12w, and UST q8w, respectively (P < 0.001 for both q12w and q8w). MH was achieved at Week 44 in 24.1%, 38.8%, and 45.9% of pts treated with placebo, UST q12w (P = 0.002), and UST q8w (P 0.001), respectively. HI at Week 44 (irrespective of maintenance treatment) was significantly associated with EI and MH (P < 0.001) and with both lower absolute levels and larger post-treatment changes in total Mayo score, partial Mayo score, and Mayo symptom sub-scores for stool frequency and rectal bleeding at Week 44. Both EI and HI following 8 weeks of UST treatment were associated with clinical remission and steroid-free clinical remission at Week 44 (P < 0.05), as well as remission through Week 44 (i.e., at both Week 8 and Week 44). For example, 26% of pts with induction HI were in clinical remission through Week 44, versus 4% of pts without induction HI. Induction MH was similarly associated with positive outcomes at maintenance Week 44.

CONCLUSION:

Among pts with moderately-to-severely active UC, those receiving SC UST maintenance had higher rates of EI, HI, and MH than those receiving placebo. Both EI and HI are associated with subsequent clinical remission and steroid-free clinical remission.
644 Incidence of Venous Thromboembolic Events in Patients With Ulcerative Colitis Treated With Tofacitinib in the Ulcerative Colitis Clinical Development Program
Authors: Sandborn William J. , Panés Julian , Sands Bruce E. , Reinisch Walter , Su Chinyu , Lawendy Nervin , Koram Nana , Fan Haiyun , Jones Thomas V. , Modesto Irene , Quirk Daniel , Danese Silvio
Published: October 2019

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). A safety signal for pulmonary embolism (PE) was seen in the tofacitinib 10 mg twice daily (BID) arm of an FDA post-marketing requirement study in rheumatoid arthritis designed to evaluate the long-term risk of major cardiovascular events and malignancy. Patients (pts) eligible for this ongoing, open-label, safety-endpoint-driven study had to be ≥50 yrs of age, have ≥1 cardiovascular risk factor and be on a stable dose of methotrexate. UC is a known risk factor for deep vein thrombosis (DVT) and PE.
1,2
We report the incidence of DVT and PE in the tofacitinib UC clinical program, as of Sep 2018.

METHODS:

DVT and PE events were evaluated from 4 randomized placebo-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], 1 maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612).
3–5
Three cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study), and Overall (pts receiving tofacitinib 5 or 10 mg BID in P2, P3, or OLE studies). Incidence rates (unique pts with events per 100 pt-yrs [PY] of exposure) were evaluated. For Overall Cohort analysis, pts were categorized based on the average daily dose of tofacitinib: predominant dose (PD) tofacitinib 5 mg or 10 mg BID.

RESULTS:

1157 pts were evaluated for DVT and PE, with 2404 PY of tofacitinib exposure and up to 6.1 yrs of treatment. In the Induction and Maintenance Cohorts, 2 pts had DVT and 2 had PE; all had received placebo in the study (Table 1). In the Overall Cohort, DVT occurred in 1 pt and PE in 4 pts during the OLE study; all pts had received PD of tofacitinib 10 mg BID. All pts with PE and DVT had risk factors for venous thrombosis (Table 1).

CONCLUSION:

In this post hoc analysis of pts with UC during tofacitinib exposure, 4 pts had PE and 1 pt had DVT, all of which occurred during the OLE study, in pts treated with PD of tofacitinib 10 mg BID (83% of Overall Cohort pts received a PD of tofacitinib 10 mg BID) with risk factors for venous thrombotic events. This analysis is limited by small sample size and limited drug exposure, and further study is needed.
647 Risk of New or Recurrent Cancer in Patients With Inflammatory Bowel Disease and Previous Cancer Exposed to Vedolizumab or Ustekinumab
Authors: Pang Alice , Hudesman David P. , Chang Shannon , Axelrad Jordan E.
Published: October 2019

INTRODUCTION:

Previous studies have demonstrated that exposure to anti-TNFα and/or immunomodulators for inflammatory bowel disease (IBD) following a diagnosis of cancer was not associated with an increased risk of new or recurrent cancer. There is little data regarding the use of newer biologics, vedolizumab and ustekinumab, after a diagnosis of cancer. We aimed to investigate whether patients with IBD and a history of cancer who were subsequently exposed to vedolizumab or ustekinumab have an increased risk of developing new or recurrent cancer.

METHODS:

We reviewed the medical records of 5062 patients with IBD and cancer from an academic medical center between January 2013 and November 2018 to identify IBD patients who received vedolizumab or ustekinumab following a diagnosis of cancer. We collected demographic, IBD and cancer-related data. Our primary outcome was the development of new or recurrent cancer. Results were compared to historical data regarding the risk of new or recurrent cancer in patients exposed to anti-TNFα, an immunomodulator or no therapy for IBD following a diagnosis of cancer.

RESULTS:

We identified IBD patients who received vedolizumab (n = 59) or ustekinumab (n = 18) monotherapy following a diagnosis of cancer (Table 1). The median age at cancer diagnosis was 51 years (IQR 43-65) for vedolizumab and 57 years (IQR 55-66) for ustekinumab. During a median follow-up of 68 months (IQR 21-132) for vedolizumab and 48 months (IQR 12-96) for ustekinumab, 3 (5%) and 3 (17%) patients developed subsequent cancer, respectively. Compared to historical data, there were differences in subsequent cancer risk between exposure groups (Figure 1; log-rank 0.001). However, when adjusted for stage of prior cancer, compared to no therapy, there was no difference in risk of new or recurrent cancer between patients exposed to vedolizumab (HR 0.01, 0.01-7.58), ustekinumab (HR 0.85, 0.11-6.50), anti-TNFα (HR 0.60, 0.34-1.07) or immunomodulators (HR 1.01, 0.58-1.75) following a diagnosis of cancer.

CONCLUSION:

In this single-center study, exposure to vedolizumab or ustekinumab in patients with IBD and a history of cancer conferred a low risk of new or recurrent cancer. Exposure to vedolizumab or ustekinumab monotherapy was not associated with an increased risk of subsequent cancer compared to historical data of exposure to anti-TNF, immunomodulators or no immunosuppression following a diagnosis of cancer. Larger studies are needed to confirm these findings.
648 Outpatients With Inflammatory Bowel Disease Are More Likely to Have Viral and Multiple Enteric Infections Identified on Multiplex PCR Pathogen Panel Testing
Authors: Hong Soonwook , Main Michael , Hine Ashley M. , Hudesman David P. , Chang Shannon , Axelrad Jordan E.
Published: October 2019

INTRODUCTION:

Gut microbial dysbiosis and impaired mucosal immunity play a major role in the pathogenesis of inflammatory bowel disease (IBD). Previous research has shown that IBD patients experience greater disease burden from gastrointestinal infections. The increasing availability of gastrointestinal multiplex polymerase chain reaction stool panels (GI PCR) has allowed for the rapid and accurate identification of viral, bacterial, and parasitic pathogens not readily diagnosable with conventional stool testing. We aimed to characterize the burden and risk factors for gastrointestinal infections on outpatients with and without inflammatory bowel disease presenting with symptoms of acute gastroenteritis.

METHODS:

We performed a cross-sectional review of outpatients presenting with gastroenteritis to an academic medical center from September 2015 to March 2019 who received a FilmArray GI PCR. Baseline demographics, presence of IBD and disease characteristics, risk factors including travel history, sexual activity, HIV status, and symptoms on initial presentation were recorded. The primary outcome was the detection of an enteric pathogen. Secondary outcomes include the class of pathogen detected, i.e., viral, bacterial, parasitic. T-test and Chi-square analysis were used to compare outcomes between groups.

RESULTS:

We reviewed 815 outpatients who received GI PCR testing, of whom 94 (12%) were diagnosed with IBD. Patients with IBD were more likely to present to the initial visit with bloody diarrhea (46% vs. 8%, P < 0.001), hematochezia (15% vs. 6%, P = 0.001), and fever (23% vs. 9%, P < 0.001; Table 1). Of outpatients with IBD, 33 (35%) had a gastrointestinal pathogen detected compared to 216 (30%, P = 0.190) of non-IBD outpatients. Patients with IBD were more likely to have viral (28% vs. 18%, P = 0.044) or multiple pathogens (11% vs. 6%, P = 0.028) and less likely to have bacterial (61% vs. 73%, P = 0.920) and parasitic infections (0 vs. 6%, P = 0.382) on GI PCR (Table 2). There were no statistically significant differences in gender, race, travel history, sexual activity, HIV status, or rate of pathogen detection between patients with and without IBD.

CONCLUSION:

Enteric infections were common in outpatients with and without IBD. IBD patients presented with more viral and multiple pathogens on GI PCR testing compared to non-IBD controls. Further studies are needed to investigate the impact of these different enteric pathogens on clinical management and disease burden.
651 Bridges to Excellence (BTE) Quality Indicators in Inflammatory Bowel Disease (IBD) in Gastroenterology Fellows' Clinic at the University of Oklahoma Health Sciences Center: A Quality Improvement Project
Authors: Salem George , Ali Ijlal , Grossen Alyssa , Bitar Hussein , Kastens Donald J.
Published: October 2019

INTRODUCTION:

The American Gastroenterology Association (AGA) Bridges to Excellence (BTE) Inflammatory Bowel Disease (IBD) Care Recognition program encourages clinicians to develop a superior quality of care in the management of IBD. The compliance to AGA quality metrics has been historically low in general gastroenterology (GI) clinics. We evaluated adherence to BTE measures in the care of IBD patients seen at a tertiary care hospital gastroenterology fellows' clinic, and developed a provider-friendly template to further increase compliance.

METHODS:

Patients with diagnosis of IBD (Crohn's disease (CD), Ulcerative Colitis (UC), or indeterminate colitis (IC)) were identified in the gastroenterology continuity clinic using ICD-9 and ICD-10 codes at the University of Oklahoma Health Sciences Center, Gastroenterology fellow's clinic. Baseline patient characteristics and 8 BTE measures were recorded. Based on compliance with quality metrics, a simple, provider-friendly template was added to GI initial and return clinic notes. Overall adherence to BTE measures and average scores as per the AGA 100 point scale were evaluated and compared pre- and post-intervention.

RESULTS:

50 patients were seen in GI fellows' clinic over 6-month period in the pre-intervention phase, and 35 were seen in the post-intervention phase. Baseline characteristics for both groups were similar. Overall adherence to BTE measures was 54%, and average BTE score was 58.8 (3 star) in the pre-intervention phase. Overall adherence to BTE measures was 42.4%, and average BTE score was 53 (3 star) (P > 0.05) in the post-intervention phase. On sub-group analysis, it was found that only half of the patients had had the intervention implemented for their care (18/35). Sub-group analysis of patients where template was implemented, adherence to BTE measures was 98.4% and average BTE score was 98.5 (5 star) (P = 0.02). When compared to the group of patients where template was not used, the overall adherence was 42.4%, and average BTE score of 53 (3 star). This was found to be statistically insignificant when compared to pre-intervention group (P = 0.60).

CONCLUSION:

The care for IBD patients continues to be a multi-disciplinary, complex approach. Using template increased compliance to vaccination and tobacco screening/counselling in our cohort. Using a provider-friendly template may improve compliance with AGA quality metrics for the care of IBD patients in outpatient settings.
653 Crohn's Disease Mortality and Ambient Air Pollution in New York City
Authors: Feathers Alexandra , Lovasi Gina , Beem Kade , Grigoryan Zoya , Datta Samit K. , Faleck David , Socci Thomas , Swaminath Arun
Published: October 2019

INTRODUCTION:

Recent years have seen an increase in the prevalence of Crohn's Disease (CD), along with drastically rising modernization at a pace not seen before, and an accompanying decline in air quality. Air pollution has been shown to affect epithelial cell function and modulate immune responses, as well as change the composition of enteric microbiota. In epidemiologic studies, ambient air pollution has demonstrated a weakly positive relationship with incident CD cases, along with CD hospitalizations. However, to date, there are no data on the associated risk of CD-related death in relation to air pollution exposure.

METHODS:

We conducted an ecologic study comparing the number of CD deaths of individuals residing in given zip codes, with the level of air pollution from NO, NO2, SO2, and fine particulate matter (PM2.5). Cases consisted of any patients with CD mentioned on their death certificate who died in New York City between 1993-2010. Zip code was assigned by patient residence. Air pollution was measured by the New York Community Air Survey. We conducted Pearson correlations, and a Poisson regression with robust standard errors. Each component of pollution was modeled separately.

RESULTS:

There was a higher risk of CD-related death among individuals living in zip codes with higher levels of SO2 (IRR 1.16, Cl 95% 1.06-1.27). Zip codes with higher percentage of Black and Latino residents were associated with lower rates of CD-related death in the SO2 model (IRR .58 Cl 95% .34-.98, IRR .14 Cl 95% .06-.33). There was no significant association of either population density or area-based income with the CD-related death rate. NO, NO2, and PM2.5 were not associated with a higher risk of death.

CONCLUSION:

In New York City from 1993-2010, CD death rates were higher among individuals from neighborhoods with higher levels of SO2, and lower among those from neighborhoods with predominately Black or Latino residents. CD death rates were not associated with levels of NO, NO2, or PM2.5. These findings raise an important and timely public health issue regarding exposure of CD patients to environmental SO2, and suggest that this area of Crohn's Disease research needs further exploration.
654 Improving Inflammatory Bowel Disease Care: A Quality Improvement Project for Venous Thromboembolism Prophylaxis
Authors: Penninti Pranav , Patel Chirag , Coss Elizabeth
Published: October 2019

INTRODUCTION:

Inflammatory Bowel Disease (IBD) patients admitted with a flare are 5-6x more likely to have a complication with venous thromboembolism (VTE). As a result, more emphasis is being placed on administering chemical prophylaxis to these patients. A 6-month retrospective chart review of patients hospitalized at our institution with an IBD flare without severe GI bleeding revealed that only 39% received chemical VTE prophylaxis. Herein, we designed a quality improvement project with an aim to improve this rate to over 75%.

METHODS:

Our initial Ishikawa diagram was used to map out the entire process from which a patient enters the emergency room until they are admitted to their hospital bed to analyze reasons DVT chemoprophylaxis was withheld. “Bleeding” was the most commonly documented reason. We then decided to target the patient population to hospitalized IBD flares without severe GI bleeding. The parameters we set for this included Hemoglobin <7 g/dL, tachycardia, and/or hypotension. Our main intervention was placing reminder sheets in each Internal Medicine team room with the aforementioned parameters for appropriate use of chemical prophylaxis. Further, a department-wide e-mail was sent to all of Internal Medicine with the reminder sheet attached and educational text.

RESULTS:

Over the 4 months post-intervention, VTE prophylaxis rates for hospitalized IBD flares without severe bleeding (n = 14) improved to 100%. Hospitalization related costs for a diagnosis of “DVT” or “PE” are reportedly ∼$10,000 & $20,000, respectively. The cost of Lovenox for a 5 day length of stay for an 80 kg man is $420. There is an estimated 7.6 to 41% risk of VTE amongst patients hospitalized for flares. At University Hospital, we averaged about 4 flares without severe bleeding/month. Using 25% risk for 48 patients per year, this could potentially lead to 12 VTE prevented/year. Taking all of this into account there is a potential 900% return on investment with savings of about $160,000/year.

CONCLUSION:

It does appear that our interventions helped us reach our goal to improve VTE prophylaxis rates in IBD flares. A weakness, however, is the low sample size of patients, but we do plan to continue collecting data over the next year. Further, education has been proven to be a weak intervention with poor sustainability in the world of QI. The main plan for sustainability remains to work with IT to implement “IBD flare without severe bleeding” as a check-mark for high-risk of VTE on the admission order set.
657 Ulceration of the Pre-Pouch Ileum in Patients With Ulcerative Colitis Following Proctocolectomy With Ileal Pouch-Anal Anastomosis: An Analysis of Pouchoscopies From 272 Patients
Authors: Ollech Jacob E. , Akyiama Shintaro , Rai Victoria , Cohen Russell D. , Hurst Roger D. , Hyman Neil H. , Dalal Sushila R. , Rubin David T.
Published: October 2019

INTRODUCTION:

Colectomy is required in up to 30% of patients with ulcerative colitis (UC) due to medically refractory disease or development of dysplasia/cancer. In such cases, restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice. However, pouchitis may occur in up to 80% of patients and significantly impairs quality of life. Pouchitis usually spares the pre-pouch ileum, however, a subset of patients develops discrete ulcerations in the pre-pouch ileum despite a firm preoperative UC diagnosis. The prevalence of such findings and predictive factors have not been adequately studied. We report a large cohort of patients undergoing pouchoscopies and describe the prevalence of pre-pouch ileal ulcerations.

METHODS:

This is a retrospective single-center study of adult patients with UC who had a total proctocolectomy with IPAA and subsequently underwent pouchoscopy between January 2007 and August 2018. At our institution, pouchoscopies are performed using a standard operating protocol. These reports include detailed descriptions of the mucosa as well as high definition images of the different areas of the pouch, the pre-pouch ileum, the pouch inlet, forward view of the pouch, a retroverted view of the pouch, and the rectal cuff. Based on these images and descriptions, we characterized pouch phenotypes and ulcer locations. Patient demographic and clinical data were also assessed.

RESULTS:

We reviewed the pouchoscopies of 272 patients who underwent proctocolectomy with IPAA for a pre-operative diagnosis of UC. Characteristics of the patients included median age 39 years (IQR 30.2-50.7), median BMI 25 (IQR 22.5-28.6), 90% Caucasian, 59% men, 23% ex-smokers and 83% extensive colitis prior to colectomy. 18% of our patients had discrete ulcerations in their pre-pouch ileum. In a multivariate analysis including age, sex, BMI, disease extent, race, ex-smoking status, prior treatment with anti TNFs or immunomodulators, history of PSC and previous infection with C. diff, none of these factors were associated with pre-pouch ileal ulcers (Table 1).

CONCLUSION:

Despite a firm diagnosis of UC prior to colectomy, 18% of patients at our tertiary center were found to have discrete ulcers in their pre-pouch ileum. We did not identify predictive factors in this patient cohort, but the potential impact of these findings suggests that proactive post-operative monitoring may be helpful.
658 Epidemiology of Major Depressive Disorder, Anxiety Disorder, and Bipolar Disorder in Ulcerative Colitis 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 ulcerative colitis (UC) are at an increased risk for developing various psychiatric illnesses including major depressive disorder (MDD), anxiety disorder, and bipolar disorder. However, these studies have been limited by a small sample size. We aimed to describe the epidemiology of psychiatric illness in UC 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 UC and depression, anxiety, and bipolar disorder between 2014 and 2019 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 UC. We calculated the overall prevalence of depression, anxiety, and bipolar disorder in UC amongst various patient groups. We also performed univariate analyses to identify risk factors for psychiatric illness in UC.

RESULTS:

Of the total number of patients in the database with UC, 22,780 had depression, 28,480 had anxiety, and 5,140 had bipolar disorder, with prevalences of 17%, 23%, and 4%, respectively. Depression, anxiety, and bipolar disorder in UC were more prevalent than in individuals without UC. Within UC, psychiatric illness was more prevalent in elderly (age >65 years old), females, and Caucasians. Compared to patients with psychiatric illness without UC, patients with psychiatric illness and UC 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 UC. Individuals with UC were more likely to suffer from depression, anxiety, and bipolar disorder compared to their non-UC counterparts. Prevalence of psychiatric illness in UC was more common in elderly, females, and Caucasians. Psychiatric illness is under recognized in UC and should be screened for and treated accordingly.