bluuebunny/crossref_metadata_2025_split huggingface dataset:
743 The Socioeconomic Impact of Living With Ulcerative Colitis: A Burden of Illness Study
Authors: Limdi Jimmy K. , Rose Alison , Noone Declan , Avedano Luisa , Hayee Bu , Sturm Andreas , Peyrin-Biroulet Laurent , Finnegan Alan , Tucknott Seb , Burisch Johan , Lobo Alan J. , Terry Helen , Fiorino Gionata , Evans Jonathan 
Published: October 2019

INTRODUCTION:
The living with Ulcerative Colitis (UC), identifying the socioeconomic burden in Europe (LUCID) study was a descriptive, retrospective, cross-sectional, European, multi-site, bottom-up Burden of Illness research study carried out by HCD Economics and the University of Chester in partnership with Crohn's and Colitis UK.

METHODS:
The primary objective of the LUCID study was to quantify the existing UC-related costs for each country and by disease severity. The study population was recruited through gastroenterologists (surveyed between Aug 2018-Feb 2019) and included adult patients diagnosed with UC by endoscopy and histology, at least 24 months prior the index date (date of clinical consultation). The study cohort population consisted of two arms; Arm 1: Patients with moderate or severe UC status at initiation of documentation period (12 months prior the index date) and, Arm 2: Patients with moderate or severe UC that achieved mild UC or remission at initiation of documentation period. Physician completed questionnaires (CRF) captured clinical information, direct medical costs and some direct non-medical costs. Patients completed a corresponding public patient involvement and engagement (PPIE) form which captured further direct non-medical costs and indirect costs. The economic burden per-patient was calculated by multiplying the quantities of the resource use collected with the national unit price. Total costs could only be calculated for patients with completed PPIE forms.

RESULTS:
Completed physician-reported forms (CRF) and PPIE forms were assessed for 1,658 patients. Of these, 1001 (60.7%) and 648 (29.3%) patients were in arm 1 and arm 2 respectively, with 9 patients unable to be assigned to either arm. Total average EU cost per patient in the last 12 months was €8,833.94 in arm 1 and €6,512.74 in patients in arm 2 with direct medical costs per patient amounting to €4381.70 in arm 1 and €3078.48 in arm 2. Direct non-medical costs per patient were €1353.93 for arm 1 and €1128.37 for arm 2. Societal costs per patient amounted to €3098.31 of the total cost for arm 1 and €2305.89 for arm 2.

CONCLUSION:
These preliminary results suggest that non-medical costs and indirect costs make up substantial proportions of the overall cost implying that the cost of treatment constitutes only a part of the overall burden of UC. Further analysis is planned to identify the drivers of costs in each arm in order to make comparisons between them.
746 Adalimumab Concentrations Following Dose Escalation in Inflammatory Bowel Disease
Authors: Jasurda Jake , McCabe Robert , Vaughn Byron 
Published: October 2019

INTRODUCTION:
Therapeutic drug monitoring is frequently performed for the management of inflammatory bowel disease (IBD). Adalimumab (ADA) concentrations of 12-16 ug/ml have been associated with clinical and endoscopic remission in Crohn's disease (CD) and ulcerative colitis (UC). The feasibility of achieving these concentrations following a dose escalation is unknown. We aim to determine expected rise in serum ADA concentrations in response to increased dose frequency.

METHODS:
Patients with an established diagnosis of IBD, on maintenance ADA therapy, and two ADA trough concentrations were included. The primary outcome was change in ADA concentration following dose escalation from every other week to weekly. Patients who had two concentrations without a dose escalation served as a control. Student's t-test was used to assess for significant differences in and between patients. Exploratory logistic regression was used to assess for clinical factors predicting the ability to achieve an ADA concentration >12 ug/ml.

RESULTS:
Eighty-nine patients met inclusion criteria, 71% with CD, 23% with UC, and 6% with indeterminate colitis. Thirty six percent were on concurrent immunomodulator (IMM) therapy. Among patients on every other week ADA dosing, the initial mean ADA concentration for those who went on to a dose escalation was 3.7 ug/ml versus 9.7 ug/ml in those who did not dose escalate (P < 0.001). Following dose escalation, mean ADA concentration significantly increased by 5.7 ug/mL (P < 0.0001) compared to a significant decrease of 2.5 ug/mL (P < 0.002) in those who remained on every other week dosing. This decrease was driven by IMM de-escalation (mean decrease of 1.7 ug/ml in those without IMM change, versus 5.5 ug/ml in those who stopped IMM, P < 0.1). Exploratory logistic regression analysis identified initial ADA concentration, female sex, and ADA as first biologic as predictors of achieving an ADA concentration >12 ug/ml after dose escalation.

CONCLUSION:
Among patients with an initial low ADA concentration, a dose escalation to weekly will increase the concentration by 5.7 ug/ml on average. Without dose escalation, cessation of IMM may decrease ADA concentrations by 5.5 ug/ml. Female sex, ADA as first biologic, and initial ADA concentration of ≥4.9 ug/ml all predicted the ability to achieve a concentration of >12 ug/ml following dose escalation. The expected concentration change after ADA dose escalation can help to guide treating physicians in determining when dose escalation is appropriate.
824 Biologic Use in Pediatric Patients Newly Diagnosed With Ulcerative Colitis in the United States, 2010-2013 and 2014-2016
Authors: D'Haens Geert R. , Naegeli April , Mahoui Malika , Morton Stuart , Dong Yan , Hunter Theresa 
Published: October 2019

INTRODUCTION:
The purpose of this study is to characterize treatment patterns and sequences of biologic initiation in pediatric patients newly diagnosed with Ulcerative Colitis (UC) in the United States in 2010-2013 and 2014-2016.

METHODS:
Pediatric (0-17 years) patients with ≥2 UC diagnosis codes (ICD-9: 556.x; ICD-10:K51.x) from October 1, 2010 to September 30, 2016 were included in this retrospective analysis of medical and pharmacy claims data from the IBM Marketscan Commercial and Medicaid Claims database. Patients were excluded if they were >18 years old, had a Crohn’s disease (CD) diagnosis, had a dual UC and CD diagnosis, or did not have treatment throughout the study period. Pathway visualization techniques and subgroups analyses were conducted for the 2 years post diagnosis to compare biologic use following first diagnosis during 2010-2013 and 2014-2016. Two-sample t test were conducted for continuous patient characteristics between 2010 -2013 and 2014-2016 diagnosis periods. Chi-square tests were used for the categorical variables.

RESULTS:
A cohort of 441 UC patients were identified with 223 (50.6%) diagnosed with UC during 2010-13 and 218 (49.4%) diagnosed during 2014-16. The proportion of male patients increased from 48.9% in 2010-2013 to 56.0% in 2014-2016. Mean age at diagnosis was not statistically different during 2010-2013 and 2014-2016 (13.5 vs. 13.5 years; P = 0.92). The majority of patients initiated conventional treatment (aminosalicylates, immunomodulators, and/or corticosteroids) at the time of diagnosis. Biologic use significantly increased from 16.1% of patients in 2010-2013 to 25.7% of patients in 2014-2016. The median time to biologic treatment in the 2 years post diagnosis was 302.5 days for those diagnosed 2010-13 versus 247.5 days for those diagnosed during 2014-16 (P = 0.1). On average, patients initiated biologic treatment 54.5 days earlier when receiving a UC diagnosis during 2014-16. Infliximab was more frequently identified as the first-line biologic in the 2 years post diagnosis for those diagnosed 2010-13 and 2014-16. However, pathway visualization Sankey diagrams illustrated limited switching from one biologic to another after initiation of biologic therapy during the 2 years post diagnosis for 2010-13 (Figure 1), with no predominant sequence identified. This trend remained for the 2014-16 cohort (Figure 2).

CONCLUSION:
Biologic use among pediatric UC patients has increased in recent years; however conventional treatment is still more common at the time of diagnosis.
836 Tofacitinib Efficacy in Patients With Moderate to Severe Ulcerative Colitis: Subgroup Analyses of OCTAVE Induction 1 & 2 and OCTAVE Sustain by 5-Aminosalicylates Use
Authors: Hanauer Stephen B. , Rubin David T. , Gionchetti Paolo , Su Chinyu , Woodworth Deborah A. , Quirk Daniel , Salese Leonardo , Wang Wenjin , Marren Amy , Lawendy Nervin , Panaccione Remo 
Published: October 2019

INTRODUCTION:
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in 3 Phase 3 trials (OCTAVE Induction 1 & 2, NCT01465763 & NCT01458951; OCTAVE Sustain, NCT01458574) in patients (pts) with moderate to severe UC (1). In this post-hoc analysis, we explored tofacitinib efficacy for pts with (c5-ASA) and without (n5-ASA) concomitant 5-aminosalicylates use.

METHODS:
In OCTAVE Induction 1 & 2, pts received placebo (PBO) or tofacitinib 10 mg twice daily (BID) for 8 weeks; clinical responders were re-randomized into OCTAVE Sustain for 52 weeks and received PBO, tofacitinib 5 or 10 mg BID. c5-ASA were permitted at entry, provided doses were stable for ≥4 weeks prior to and during the trials. Remission and mucosal healing were summarized at Week 8 (OCTAVE Induction 1 & 2) and Week 52 (OCTAVE Sustain) by c5-ASA status. Generalized linear models were used to compare adjusted treatment effects between 5-ASA subgroups (Tables 1 and 2).

RESULTS:
A smaller proportion of c5-ASA pts had prior tumor necrosis factor inhibitor (TNFi) and immunosuppressant failure versus n5-ASA pts, at baseline of OCTAVE Induction and OCTAVE Sustain (OCTAVE Induction 1 & 2: TNFi failure, 42.7% vs 74.5%; immunosuppressant failure, 69.4% vs 78.3%; OCTAVE Sustain: TNFi failure, 36% vs 70%; immunosuppressant failure, 67.9% vs 80%). For both the 5-ASA subgroups, a higher proportion of tofacitinib-treated pts achieved efficacy endpoints, versus PBO-treated pts, at Week 8 of OCTAVE Induction 1 & 2 and Week 52 of OCTAVE Sustain (Tables 1 and 2). Without controlling for baseline variables, higher treatment effects were observed within the c5-ASA subgroup versus the n5-ASA subgroup. When controlled for prior TNFi and immunosuppressant failure (and baseline remission status in OCTAVE Sustain), the differences were not statistically significant in treatment effects between the 5-ASA subgroups in terms of adjusted odds ratios (Tables 1 and 2).

CONCLUSION:
When controlling for prior UC treatment status, efficacy of tofacitinib, based on adjusted odds ratios, was similar regardless of 5-ASA status. These post-hoc analyses were not intended to evaluate incremental benefit of 5-ASA as combination therapy for tofacitinib.
841 The Impact of Inpatient Intravenous Opioids on Future Outpatient Opioid Exposure Among Hospitalized Patients With Inflammatory Bowel Disease
Authors: Dalal Rahul S. , Palchaudhuri Sonali , Snider Christopher , Lewis James , Mehta Shivan , Lichtenstein Gary R. 
Published: October 2019

INTRODUCTION:
Patients hospitalized for inflammatory bowel disease (IBD) often receive opioids (OPIs) to control pain. However, OPI use is associated with excess mortality and infections in IBD patients (AJG 2012;107(9):1409-22). Given the high potency of intravenous (IV) OPIs and their unclear impact on future OPI exposure, we sought to determine if IV OPI use is associated with subsequent outpatient OPI prescriptions (Rx) among hospitalized IBD patients.

METHODS:
We performed a retrospective cohort study of patients aged >18 years hospitalized at a large urban academic health system from 3/1/17 to 4/10/18. Patients were included if they were admitted to observation, general medical, general surgical, or gastrointestinal surgical services, had a discharge diagnosis of IBD, and had >1 outpatient office visit in the department of gastroenterology within 12 months of discharge. IBD history, patient-reported pain scores, and demographic, medication administration, and outpatient Rx data were abstracted from the electronic health record. We used multivariable mixed effect logistic regression modeling (MVMELR) to account for repeat encounters and to assess the association between IV OPI exposure and an outpatient OPI Rx provided within 12 months after discharge while adjusting for confounders. IV OPI exposure was represented both as a binary variable and a continuous variable in total IV morphine mg equivalents/length of stay in days (IVMMEs/d). Kaplan-Meier (KM) analysis was performed to compare time to outpatient OPI Rx by inpatient OPI exposure.

RESULTS:
We included 709 encounters among IBD patients between 3/1/17 and 4/10/18. Patient characteristics and unadjusted outcomes by OPI exposure are presented in Table 1. MVMELR demonstrated a significant association between IV OPI exposure (binary predictor: OR 2.9, 95% CI 1.4-5.9; continuous predictor in IVMMEs/d: OR 1.0, 95% CI 1.0-1.1) and an outpatient OPI Rx within 12 months of discharge. Receiving only non-IV OPIs was not associated with an opioid Rx (OR 0.8, 95% CI 0.3-2.4; Table 2). KM analysis demonstrated significant separation in rate curves for OPI Rx between OPI exposure groups (log rank test P < 0.01; Figure 1).

CONCLUSION:
Administration of IV OPIs to hospitalized IBD patients may increase their risk for further OPI exposure after discharge. IV OPIs should be used judiciously in this high-risk population with consideration of appropriate alternatives. Additional research is needed to identify long-term risks of IV OPI use in patients with IBD.
849 Risk of Reoccurrence of Perianal Fistulas in Patients With Crohn’s Disease in the United States: A Retrospective Claims Database Study
Authors: Patel Haridarshan , Latremouille-Viau Dominick , Serre Didier , Lissoos Trevor , Null Kyle D. , Owen Glynn , Campbell-Hill Sarah 
Published: October 2019

INTRODUCTION:
Perianal fistulas (PAF) in patients with Crohn’s disease (CD) are associated with morbidity and impaired quality of life. Limited data is available on the risk of PAF among patients with CD and long-term PAF relapse rates.

METHODS:
A retrospective cohort study on US adult patients with CD identified in an US administrative claims database (2001-2018) was conducted. Patients with PAF were identified using diagnosis or procedure codes in medical claims. A PAF episode, starting from the first PAF occurrence, was defined as consecutive PAF-related codes ≤120 days of each other. PAF reoccurrence was defined as a new PAF-related code occurring after a PAF-free period of ≥180 days (proxy for remission) following the end of the first PAF episode. Time from the 180-day PAF-free period to PAF reoccurrence was estimated using KM analyses. A similar analysis was conducted in CD patients with a PAF-free period of ≥360 days.

RESULTS:
5,482 patients with a PAF-free period of ≥180 days after their first PAF episode were included (CD-PAF cohort; mean age = 43.8 years and proportion of males = 51.8%). Over a mean follow-up duration of 2.6 years, 28.8% had a PAF reoccurrence. Estimated rates of PAF reoccurrence in these CD-PAF patients were 23.7%, 32.0%, 42.1% and 47.8% at 1, 2, 5, and 10 years, respectively (Table 1). In the 12 months before first PAF occurrence, 70.8% of CD-PAF patients received non-biologic therapies: corticosteroids (46.5%), antibiotics (44.4%), aminosalicylates (5-ASA) (32.5%) and immunomodulators (IMDs)/immunosuppressants (IMs) (21.1%); 25.3% used ≥1 biologic therapy; and 19.2% had ≥1 CD-related surgery. In the 4 months after first PAF occurrence, 66.5% of CD-PAF patients received non-biologic therapies: antibiotics (39.6%), corticosteroids (30.3%), 5-ASA (27.4%) and IMDs/IMs (22.1%); 31.8% used ≥1 biologic therapy; and 47.2% had ≥1 CD-related surgery. In patients with a longer PAF-free period of ≥360 days (CD-PAF360 cohort), a numerically lower proportion had a PAF reoccurrence (20.5%) and estimated rates of reoccurrence were numerically lower at every time point (32.6% at 5 years and 39.4% at 10 years) vs the CD-PAF cohort.

CONCLUSION:
In this retrospective US claim database analysis, the 5-year and 10-year rates of PAF reoccurrence following PAF remission of ≥180 days were 42.1% and 47.8% among patients with CD, respectively. Patients achieving longer-term remission (≥360 days) had numerically lower rates of PAF reoccurrence.
901 Luminal-Apposing Stents for Benign Intraluminal Strictures: Are We There? U.S. Multicenter Study
Authors: Mizrahi Meir , Kumar Manoj , Tharian Benjamin , Khan Salman Ali , Inamdar Sumant , Sharma Neil , Uppal Dushant , Shami Vanessa M. , Kashif Mahmood Syed , Gabr Moamen , Pleskow Douglas , Berzin Tyler M. , Adler Douglas G. 
Published: October 2019

INTRODUCTION:
Benign gastrointestinal (GI) strictures may occur anywhere in the GI tract but are more common in the upper GI tract or post-surgery. Large amount of these strictures will be resistant for conventional treatments such as balloon or mechanical dilation, incisional therapy, steroid injection, and conventional stents. Recently few small studies reported the use of fully covered lumen-apposing metal stents (LAMS) for benign short strictures. The aim of this study was to evaluate the safety and efficacy of LAMS for refractory GI strictures.

METHODS:
Patients and Methods Consecutive patients who underwent LAMS placement for various benign strictures seven tertiary care centers were reviewed retrospectively. The primary outcomes were technical success and initial clinical success of LAMS placement. Secondary outcomes were stent migration, rate of re-intervention, and adverse events.

RESULTS:
Results A total of 51 patients underwent 54 LAMS placement procedures. Median length of the stricture was 8 mm. Previous treatment had failed in 61% of patients. Location of the stricture was found to be at the level of esophagogastric or gastro-Jejunal anastomosis, Pylorus, Ileo-colonic and other in 25%, 21%, 41%, 8% and 5% respectively. A 15 mm × 10 mm LAMS was placed in 32 patients (63%) and a 20 mm × 10 mm LAMS was placed in 19 patients (37%). Median procedure time was 29 min (20-64min). Technical success was achieved in 100% of procedures and initial clinical success was achieved in 98.2% of all procedures. Patient initial clinical success was 49/51 (96%). Mean (range) stent indwell time was 56 (3-126) days. No stent migration occurred during the study period. Adverse events were noted in 10/51 of 25 patients (19%) including pain requiring removal, 1 pain not requiring removal 7; new stricture formation, 1; bleeding, 1). Median follow-up was 162 days after stent placement.

CONCLUSION:
LAMS are safe and effective in the treatment of short benign GI strictures. The use of larger diameter LAMS such as the new 20mm length my improve outcome and reduce the need of re-intervention. Large prospective studies to the determine the optimal stent size and length of treatment are required.
916 Endoscopic Fistulotomy vs. Redo Surgery for the Treatment of Pouch-to-Pouch Fistula in Patients With Inflammatory Bowel Disease
Authors: Lan Nan , Shen Bo 
Published: October 2019

INTRODUCTION:
Pouch-to-pouch fistula is a rare yet challenging complication in patients who underwent ileal pouch-anal anastomosis. The aim of this study was to compare endoscopic fistulotomy and redo pouch surgery in the management of pouch-to-pouch fistula.

METHODS:
All consecutive patients with pouch-to-pouch sinuses treated with endoscopic fistulotomy vs. redo surgery from 2000 to 2018 were identified. The primary outcomes were surgery-free survivals and post-procedural complications.

RESULTS:
This historical cohort study included a total of 59 patients (endoscopic fistulotomy, N = 40 and redo surgery, N = 19). Complete resolution of the fistula was achieved in 29/37 (78.4%) patients, partial healing was seen in 8/37 (21.6%) patients with endoscopic fistulotomy while an initial complete healing was obtained in all patients receiving redo surgery. During a foolow-up of 1.4 years, subsequent surgery was needed in 4 (10.0%) patients with endoscopic fistulotomy and 4 (21.1%) patients with initial redo surgery (P = 0.45). Kaplan-Meier surgery-free survivals after initial procedure showed no statistical difference between the two groups (P = 0.42). The rate of adverse events in the endoscopic fistulotomy group was significantly lower than that in the surgery group (5.6% vs. 68.4%, P < 0.001). Patients receiving redo surgery had complications of a higher Clavien-Dindo class as well.

CONCLUSION:
Surgery-free survival were comparable between patients treated with endoscopic fistulotomy and redo surgery, while pouch redo surgery was found to be associated with a higher immediate complete healing rate yet a higher morbidity.
951 Immune Checkpoint Inhibitors-Related Gastrointestinal Toxicity Is Associated With Better Overall Survival and Treatment Response in Cancer Patients
Authors: Alomari Mohammad , Al Ashi Suleiman , Al Momani Laith , Nehme Fredy , Sarmini Muhammad Talal , Young Mark , Funchain Pauline , Romero-Marrero Carlos 
Published: October 2019

INTRODUCTION:
Immune checkpoint inhibitors (iCPI) have recently gained an essential role in treating cancer at advanced stages. However, it has been associated with the development of gastrointestinal immune-related adverse events (GI-IrAEs). We aimed in our study to assess the incidence and nature of GI-IrAEs as well as to investigate the effects of developing GI-IrAEs on cancer response to iCPI and overall survival.

METHODS:
We retrospectively identified adult patients diagnosed with end-stage malignancy who were treated with any iCPI at our tertiary center between 8/2014 and 8/2017. Charts were reviewed for baseline characteristics, immunotherapy regimens, response to treatment, development of GI-IrAEs, and patient’s overall 1-year survival. Patients in whom the etiology of GI-IrAEs was unclear were excluded. The overall 1-year survival was calculated from the date of treatment initiation and estimated by the Kaplan-Meier method.

RESULTS:
We included 492 patients with end-stage cancer receiving iCPI. The majority of patients were white 451(92%) with a median age of 64.5 years. (Table 1) GI-IrAEs were in the form of autoimmune hepatitis 18(48.5%), autoimmune colitis 16(43.5%), autoimmune pancreatitis 4 (11%), and a combination of autoimmune colitis and hepatitis in 1 patient. (Figure 1) Brain cancer was associated with the highest risk of GI-IrAEs 16 (44.4%) followed by renal cell carcinoma 7 (19.4%). Nivulomab was associated with the highest risk for GI-IrAEs (55.6%) followed by Pembrulizumab 14 (38.9%). Forty-one percent of Patients who developed GI-IrAEs had an adequate cancer response to immunotherapy compared to 25.7% in patients without GI-IrAEs (P-value = 0.022). Eighty- three percent of patients whose cancer responded to iCPI survived at 1 year compared to 36 % among non-responders (P < 0.0001). Seventy-eight percent of patients who developed GI-IrAEs survived at 1 year compared to 53% in patients without GI-IrAEs (P < 0.005).

CONCLUSION:
The incidence of gastrointestinal toxicity associated with iCPI is second only in frequency to dermatological toxicity. In our study, among the white population with end-stage cancer receiving iCPI, autoimmune hepatitis, colitis, and pancreatitis were fairly common and associated with better cancer response to immunotherapy and overall survival at 1 year. GI-IrAEs might be an indicator of immune system activation, thus may be a reason to continue, rather than discontinue, immunotherapy agents as tolerated.