bluuebunny/crossref_metadata_2025_split huggingface dataset:
753 Public Cervix Announcement: Provider Gender May Influence Cervical Cancer Screening in IBD Women
Authors: Kirelik Danielle , Pascual Lauren , Dawit Lillian , Borum Marie 
Published: October 2019

INTRODUCTION:
Females with inflammatory bowel disease (IBD), specifically those on immunosuppressive therapy, may be at increased risk of cervical dysplasia and cervical cancer. Women with IBD have been reported to be screened less frequently than those at average risk. In addition, annual cervical cancer screening is recommended for IBD women who are on immunosuppressive therapy. This study evaluated the influence of provider gender on counseling for cervical cancer screening in IBD women.

METHODS:
A retrospective chart review of all IBD women seen in the gastroenterology clinic at a university medical center during a 5 year period was performed. Patient age, race, IBD diagnosis, medications, primary gastroenterology provider and documentation of cervical cancer screening or counseling within the past three years were recorded. Women who had a hysterectomy or those <21 or >65 years of age were excluded. A database was generated using Microsoft Excel. Statistical analysis was performed using Fisher's Exact Test with significance set at P < 0.05. The study was approved by the institutional IRB.

RESULTS:
218 IBD women were identified, with 192 women meeting criteria for analysis. 137 (71.35%) had Ulcerative Colitis (UC), 46 (23.96%) Crohn's disease (CD), 5 (2.60%) microscopic colitis, and 4 (2.08%) indeterminate colitis. Mean age was 44.26 (range: 21-65). 98 (51.04%) were White, 53 (27.60%) Black/African American, 7 (3.65%) Asian, 6 (3.13%) Hispanic, 14 (7.29%) identified as other, and 14 (7.29%) declined to disclose. Male providers managed 125 (65.1%) and female providers managed 67 (34.9%) patients. 61 of 192 patients (31.77%) were counselled about cervical cancer screening. Female (50.75%; 34 of 67) versus male (21.6%; 27 of 125) providers counseled significantly more patients (P < 0.0001). There was no significant difference in the rate of counseling based on race (P = 0.8724), age (≤40 versus >40) (P = 0.5319), IBD diagnosis (P = 0.5863), or medication type (P = 0.6235).

CONCLUSION:
This study revealed that women with IBD were inconsistently counseled about cervical cancer screening. While female providers were significantly more likely to provide screening education, there was a clear need to improve counseling by all providers. Although this study was limited by retrospective design and single institution cohort, it highlights the need for patient education on the importance of cervical cancer screening to optimize clinical outcomes.
754 Keep IBD Flu Free: Annual Influenza Vaccination Is Inconsistently Administered to Inflammatory Bowel Disease Patients
Authors: Dawit Lillian , Kirelik Danielle , Pascual Lauren , Borum Marie 
Published: October 2019

INTRODUCTION:
It is recommended that all patients with IBD receive annual influenza vaccinations. Compared to age-matched healthy individuals, patients with IBD, particularly those on immunosuppressants, are at an increased risk of acquiring influenza. Furthermore, IBD patients who acquire influenza are more likely to be hospitalized or have a superimposed pneumonia. It is uncertain if IBD patients are consistently counselled about or administered the influenza vaccine. This study investigated rates of annual influenza vaccination in IBD patients at a university medical center.

METHODS:
A retrospective chart review evaluating all IBD patients seen in the gastroenterology clinic during a five year period was performed. Patient gender, age, race, IBD diagnosis, and documentation of flu vaccine within one year of the most recent gastroenterology visit were collected. A database was generated using Microsoft Excel. Statistical analysis using Fisher's Exact Test was performed with significance set at P < 0.05. The study was approved by the institutional IRB.

RESULTS:
392 IBD patients (218 females, 174 males) were analyzed. 206 were self-reported as White (52.55%), 99 African-American (25.25%), 11 Asian (2.81%), 35 other (8.93%), and 41 declined to disclose (10.46%). Mean age was 44.44 (range: 20-82). 279 had Ulcerative Colitis (71.17%), 96 Crohn's (24.49%), 11 Microscopic colitis (11, 2.81%), and 6 Indeterminate colitis (1.53%). 102 of 392 (26.02%) patients had a documented flu vaccine. There was a significant difference in the flu vaccination rate between patients age ≥50 (35.56%) and age < 50 (21.01%) (P = 0.0024). No significant difference was found between gender (P = 0.274), race (White vs. AA) (P = 0.274), IBD diagnosis (UC vs. Crohn's) (P = 0.416), or medications (biologics/immunomodulators vs. other) (P = 0.907).

CONCLUSION:
This study revealed that, despite current guidelines, there may be insufficient rates of influenza vaccinations among IBD patients. Individuals who were ≥50 more often had documented flu vaccination compared to younger patients. While this study it limited based upon size and single institution design, the results emphasize the need to improve administration of flu vaccine in all IBD patients. Recommendation for flu vaccination and/or assessment of the receipt of the vaccine should be performed by gastroenterologists to ensure optimal IBD health care delivery.
762 Comorbidities and Opioid Use Among Patients With Crohn's Disease
Authors: Pilon Dominic , Obando Camilo , Ding Zhijie , Voelker Jennifer , Muser Erik , Manceur Ameur M. , Kinkead Frederic , Lafeuille Marie-Hélène , Lefebvre Patrick 
Published: October 2019

INTRODUCTION:
Comorbidities associated with Crohn's disease (CD) add to the symptoms of disease and may contribute to substantial disease burden. There is a lack of information on the development of comorbidities in CD patients in the real world. This study aims to compare comorbidities, including opioid use, in CD patients relative to patients without inflammatory bowel disease (IBD), using a large database and long-term follow-up.

METHODS:
This was a retrospective matched cohort study. Working age adults with CD (≥2 independent claims with a CD diagnosis ≥30 days apart and within 1 year; first CD diagnosis was the index date) and controls without diagnosis for IBD (random index date) were identified in a US healthcare claims database (OptumHealth Care Solutions, Inc.) of privately-insured patients (01/1999-03/2017). CD patients were matched 1:5 with non-IBD controls using baseline characteristics, including the Quan-Charlson comorbidity index and cardiovascular disease. Comorbidities during the 12-month baseline period before the index date were reported. During the follow-up, lasting at least 12 months, the incidence of new comorbidity, including opioid use as a proxy for pain, was compared to the non-IBD controls by Kaplan-Meier (KM) rate with log-rank test.

RESULTS:
The study sample was composed of 6,715 CD patients and 33,575 non-IBD matched patients (average age of 45 years old, and 54% female). Pain, anemia, and fatigue were significantly higher in the CD cohort at baseline (Figure 1). Over the follow-up, new cases of cardiovascular disease were significantly higher in the CD compared to the matched non-IBD cohort with a rate of 11.5 vs 7.8%, respectively, by year 6 (Figure 2). In addition, the rates of new cases of fatigue (5.3 vs 3.2%), anemia (6.0 vs 1.9%), respiratory disease (3.5 vs 1.8%), and anxiety (5.3 vs 2.8%) were also significantly higher in the CD cohort compared to the non-IBD cohort by year 6 (log-rank P-value < 0.001). When new cases of pain diagnosis or opioid use were analyzed, the rate was significantly higher in the CD cohort, reaching 74.0% compared to 59.1% in the non-IBD cohort at year 6 (Figure 3).

CONCLUSION:
In this study, comorbidities, in particular new cases of pain diagnosis or opioid use, were significantly higher in CD patients relative to non-IBD patients, suggesting that the development of comorbidities may contribute to the long-term disease burden of CD.
767 Inflammatory Bowel Disease Patients Prior to Starting on Anti-TNF Are Over 5 Times More Likely to Be Screened for Hepatitis B Infection Compared to Those Starting High Dose Corticosteroids
Authors: Ho Edith Y. , Marshall Vanessa , Alsamman Yasser , Chung Grace , Burant Christopher , Dave Maneesh , Falck-Ytter Yngve 
Published: October 2019

INTRODUCTION:
Screening for hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients prior to initiating anti-tumor necrosis factor alpha (anti-TNF) therapy has significantly improved over the past decade. HBV screening prior to initiating high dose corticosteroids (HDC) is largely unknown despite potentially greater risks of HBV reactivation compared to anti-TNF. This study aims to determine the factors associated with HBV screening and whether the type of immunosuppression affects screening practices.

METHODS:
This retrospective chart review included Veterans with diagnostic codes for Crohn's Disease (CD: ICD-9-CM 555.x and ICD-10-CM K50.x) and ulcerative colitis (UC: ICD-9-CM 556.x and ICD-10-CM K51.x) first recorded between 01/2013 to 08/2016 at the Cleveland Veterans Affairs Medical Center. IBD patients who were started on anti-TNF or HDC were assessed whether HBV screening was conducted within 12 months of initiating therapy. HDC was defined as ≥10 mg for ≥4 consecutive weeks. Patient factors including gender, age, race, service connectivity (SC), and type of immunosuppression were assessed as independent predictors for screening.

RESULTS:
Among 571 Veterans, 56 started immunosuppression with 17 on anti-TNF and 39 on HDC. A total of 31/56 (56%) were screened: 90% male, mean age 49, 32% mean SC, 45% on anti-TNF and 55% on HDC. A total of 25/56 (44%) were not screened: 96% male, mean age 58,17% mean SC, 12% on anti-TNF and 88% on HDC. In those on anti-TNF, 88% were screened compared to 44% on HDC (P = 0.007). In multivariate analysis, immunosuppression type was significantly associated with screening where patients initiated on anti-TNF were 5.5 times more likely to be screened compared to those on HDC (OR 0.18, P = 0.025). Age, gender, race, and service connectivity did not have any impact on screening.

CONCLUSION:
Overall, 56% of IBD patients receiving immunosuppression were screened for HBV. 88% were screened prior to anti-TNF compared to 44% prior to HDC. Patients initiated on anti-TNF were over 5 times more likely to be screened compared to those on HDC. Importance of HBV screening prior to high dose corticosteroids in IBD patients should be emphasized in societal guidelines and clinical practice, given that HDC poses a potentially greater risk of HBV reactivation compared to a biologic.
770 Relationship Between Protocol Specified Corticosteroid Tapering Regimens and Achieving Outcome Measures in Patients With Moderate-Severe Ulcerative Colitis and Crohn's Disease
Authors: George John , Singh Siddharth , Dulai Parambir , Ma Christopher , Nguyen Tran , Feagan Brian G. , Sandborn William J. , Jairath Vipul 
Published: October 2019

INTRODUCTION:
Corticosteroid-free clinical remission is an important clinical outcome, yet is inconsistently defined and reported in clinical trials. We summarized the protocol specified corticosteroid tapering regimens in clinical trials of moderate-severe ulcerative colitis (UC) and Crohn's disease (CD), and calculated differences in rates of clinical remission versus corticosteroid-free clinical remission (CSF-CR).

METHODS:
Through a systematic literature review through February 28, 2019, we identified 16 randomized controlled trials (RCTs) of biologics or small molecules in patients with moderate-severe UC or CD that reported CSF-CR as an outcome. We estimated relative risk (RR) [and 95% confidence interval (CI)] of achieving CSF-CR vs. overall clinical remission in patients treated with active intervention or placebo, through random effects meta-analysis.

RESULTS:
Across trials of UC (11 trials) and CD (5 trials), median 53% (range, 28-81%) and 49% (range, 42-56%) participants were on corticosteroids at time of trial entry, respectively. Participants were allowed to enter trials at median corticosteroid dose 35 mg/d (range, 20-40 mg/d). Doses were kept stable for median 8 weeks (range, 5-10 weeks) during induction therapy, after which a mandatory and structured tapered was implemented, albeit with investigators discretion depending on clinical status. For maintenance trials, pooled rates of CSF-CR in patients with UC (n = 11) treated with placebo was 9.7% (95% CI, 6.8-13.6% vs. overall clinical remission: 14.2%; 95% CI, 10.6-18.7) and with CD (n = 5), 19.1% (95% CI, 11.3-30.2 vs. overall clinical remission: 25.7%; 95% CI, 16.4-37.7). In UC trials, the rate of CSF-CR was 24% lower than the rate of overall clinical remission (RR, 0.76; 95% CI, 0.67-0.86; placebo: RR, 0.74; 95% CI, 0.56-0.97). In patients with CD, rate of CSF-CR was 18% lower than rate of overall clinical remission (RR, 0.82; 95% CI, 0.72-0.94; placebo: RR, 0.75; 95% CI, 0.57-0.98).

CONCLUSION:
This is the first systematic review and meta-analysis to study corticosteroids handling across clinical trials. Protocol specified corticosteroid tapering regimens varies across trials with considerable investigator discretion. Rates of CSF-CR is 20-25% lower than overall clinical remission. These findings will help to inform design and interpretation of future clinical trials and highlight the need for standardization.
772 Long-Term Mucosal Healing, Clinical Response and Clinical Remission in Patients With Ulcerative Colitis Treated With the Anti-MAdCAM-1 Antibody Ontamalimab: Results From the Open-Label Extension Study TURANDOT II
Authors: Danese Silvio , Sandborn William J. , Reinisch Walter , Hébuterne Xavier , Kłopocka Maria , Tarabar Dino , Vaňásek Tomáš , Greguš Miloš , Hellstern Paul A. , Kim Joo Sung , Sparrow Miles , Gorelick Kenneth J. , Goetsch Martina , Bliss Caleb , Gupta Charu , Cataldi Fabio , Vermeire Séverine 
Published: October 2019

INTRODUCTION:
Ontamalimab (SHP647), a human monoclonal IgG2 antibody, targets mucosal addressin cell adhesion molecule-1 (MAdCAM-1), to reduce lymphocyte homing to the gastrointestinal (GI) tract. In the TURANDOT II trial, ontamalimab was well-tolerated and clinical benefit was seen up to 144 wks in patients with ulcerative colitis (UC). Here we report long-term mucosal healing, response and remission in a subset of patients in TURANDOT II.

METHODS:
TURANDOT II (NCT01771809) is a phase 2, 2-part open-label (OL) extension study of ontamalimab in patients with UC who received placebo or ontamalimab 7.5, 22.5, 75 or 225 mg in the feeder study (TURANDOT). At TURANDOT II baseline (TURANDOT wk 12), patients were randomized to ontamalimab 75 or 225 mg every 4 wks for 72 wks (OL1). In cases of clinical exacerbation or no response, escalation from 75 to 225 mg was permitted from wk 8. In OL2, patients received 75 mg every 4 wks for 72 wks. Endoscopies were carried out at wk 16, and a subset of patients undergoing routine cancer surveillance had at least one follow-up endoscopy between wks 40 and 72 of OL1: all endoscopies were centrally-read. Mucosal healing (Mayo endoscopy subscore ≤1), clinical remission (total Mayo score ≤2, no subscore >1) and clinical response (≥3-point decrease in total Mayo score from TURANDOT baseline, ≥30% change; ≥1-point decrease in or ≤1 rectal bleed absolute score) were measured.

RESULTS:
Of 330 patients in TURANDOT II, 101 had follow-up endoscopies (Table 1), 25.7% (n = 26) of whom had mucosal healing at TURANDOT II baseline. At wk 16, 43.6% (n = 44) had mucosal healing, and 33 of these patients (75%) maintained mucosal healing up to wk 40–72. Of 65 responders in TURANDOT, 37 (56.9%) had mucosal healing at both wk 16 and wk 40–72. Of 36 non-responders, 7 (19.4%) and 9 (25%) achieved mucosal healing at wk 16 and wk 40–72, respectively (Figure 1). Of the responders, 58 (89.2%) maintained response and 27 (41.5%) were in remission at wk 16; at wk 40–72, 53 (81.5%) maintained response and 33 (50.8%) were in remission. Of non-responders, 22 (61.1%) achieved response and 5 (13.9%) achieved remission by wk 16; by wk 40–72, 17 (47.2%) had responded and 8 (22.2%) were in remission. Overall, the mean Mayo endoscopic subscore of 2 (SD, 0.1) was maintained to wk 40–72.

CONCLUSION:
Mucosal healing, response and remission persisted in a subset of patients who continued ontamalimab treatment up to 72 wks and underwent surveillance endoscopies between wks 40 and 72.
774 Use of Formal Pharmacokinetic Analysis to Optimize Therapy in Patients With Secondary Loss of Response to Infliximab
Authors: Khattab Ahmed , Ehrenpreis Eli 
Published: October 2019

INTRODUCTION:
Infliximab (IFX) exhibits a wide range of inter-individual pharmacokinetic (PK) variability. During maintenance therapy, more than 50% of patients with inflammatory bowel disease have sub-optimal trough concentrations. In the 1st year of IFX therapy, 40% experience a loss of response (LOR) due to non-immune mediated PK failure from suboptimal drug exposure. Currently, dose optimization relies on dose escalation or reduction by trial and error. Our aim was to formulate a model that maximizes the efficiency of IFX dose optimization using formal PK analysis.

METHODS:
We analyzed serum IFX levels obtained during the slow-decay portion of the drug concentration-versus-time curves of 30 normal volunteers that received a single standard dose (5 mg/kg) of IFX.
1
Using Prism (GraphPad Software, Seattle, WA), we determined the minimal number of serum IFX levels required to calculate the elimination rate constant (Kel). Volume of distribution (Vd) was determined by estimating blood volume. Peak drug concentration (Peak) was calculated by dividing IFX dose by Vd. Optimal dosing interval (T) was determined by the equation: T = ln (peak/trough) ÷ Kel. The equation was used to calculate T to achieve a specific trough concentration. IFX doses required to achieve a specific trough at a predetermined time interval was also calculated.

RESULTS:
Data for all patients is shown in Table 1. Five serum levels of IFX were required to accurately determine Kel. To maintain a trough >5 µg/mL, calculated T ranged from 5.6 to 23.2 weeks. Calculated T was 7-9 weeks in 9 subjects, <7 weeks in 11 subjects and >9 weeks in 10 subjects. Conversely, optimum doses required to achieve a trough of ≥5 µg/mL with 8 week infusions ranged from 1.0 to 16.8 mg/kg (Table 2). Our model shows a direct relationship between administered doses and predicted troughs. There is a complex relationship between T and trough such that halving T usually showed a higher trough than a doubled dose (P < 0.0001, Wilcoxon matched-pairs signed-ranks test) (Figure 1).

CONCLUSION:
Using a PK approach to adjust IFX therapy eliminates the requirement for multiple optimizations, and may reduce the need to switch to different drugs after failed optimizations. Our approach has the potential to reduce costs by decreasing IFX doses in some patients, prevention of premature discontinuation of IFX, and reducing the probability of LOR from low troughs in individual patients.
775 Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease
Authors: Abu-Sbeih Hamzah , Faleck David , Ricciuti Biagio , Mendelsohn Robin , Naqash Abdul Rafeh , Cohen Justine , Sellers Maclean , Balaji Aanika , Ben-Betzalel Guy , Hajir Ibraheim , Zhang Jiajia , Awad Mark , Leonardi Giulia , Johnson Douglas , Pinato David , Owen Dwight , Weiss Sarah , Lamberti Giuseppe , Lythgoe Mark , Manuzzi Lisa , Arnold Christina , Naidoo Jarushka , Merkel Gal , Powell Nick , Yeung Sai-Ching , Sharon Elad , Dougan Michael , Wang Yinghong 
Published: October 2019

INTRODUCTION:
We characterized gastrointestinal adverse events in patients with underlying inflammatory bowel disease (IBD) who received immune checkpoint inhibitors.

METHODS:
We performed a fourteen-center, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of gastrointestinal adverse events.

RESULTS:
Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4 and 85 received monotherapy targeting programmed death-1 or its ligand. Half the patients had Crohn's disease and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12). Forty-three patients were not receiving treatment for IBD (Table 1). Gastrointestinal adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < 0.001). Gastrointestinal events among patients with IBD included grade 3 or 4 diarrhea in 21 patients. Four patients experienced colonic perforation, 2 of whom required surgery. No gastrointestinal adverse event-related deaths were recorded (Table 2). Anti-cytotoxic T-lymphocyte antign-4 therapy was associated with increased risk of gastrointestinal adverse events on univariate but not multivariate analysis (respectively, odds ratio, 3.19; 95%confidence interval, 1.8-9.48; P = 0.037 and odds ratio, 4.72; 95% confidence interval, 0.95-23.53; P = 0.058).

CONCLUSION:
Preexisting IBD increases the risk of severe gastrointestinal adverse events in patients treated with immune checkpoint inhibitors.
777 Effect of Ustekinumab Dose Escalation on Recapturing Clinical Response in Patients With Crohn's Disease
Authors: Bundschuh Mark , McDonough Gregory , Kumar Priyanka , Kozuch Patricia , Shivashankar Raina 
Published: October 2019

INTRODUCTION:
Previous studies have shown that ustekinumab (UST) is an effective induction and maintenance therapy for patients with moderate to severe Crohn's Disease (CD). We sought to examine the real-world efficacy and safety of UST and whether UST dose escalation helps to recapture clinical response.

METHODS:
All patients who received the initial weight-based UST infusion between 4/2017 and 4/2018 were identified through a query of the EMR. Patients were followed from the time they initiated UST through 5/2019 or their date of UST discontinuation, whichever came first. Specifically, patients who lost response to UST 90 mg injection every 8 wk dosing and were then dose escalated to either every 4 or 6 wk dosing were identified. Recaptured clinical response to dose escalation was determined by reviewing clinical documentation and assessing for a reduction of ≥3 in the modified Harvey Bradshaw index (mHBI) after ≥8 wks following dose escalation.

RESULTS:
We included 27 patients with CD [median age 40 (range 24-61); 56% male; 96% tumor necrosis factor (TNF)-antagonist exposed]. Table 1 compares characteristics and outcomes of patients who underwent dose escalation vs. those who remained on regular dosing. Of the 11 dose escalated patients, 9 were switched to an every 4 wk regimen while the other 2 were switched to an every 6 wk regimen. Patients who underwent dose escalation were more likely to be a smoker (18% vs. 13%), have a history of perianal disease (73% vs. 38%), have previously tried a greater number of biologics (2.7 vs. 1.9), and be exposed to concomitant steroid (55% vs. 25%). Moreover, patients who underwent dose escalation were less likely to achieve steroid discontinuation within the first 8 wks compared to those who remained on regular dosing (9% vs. 50%). The only adverse event in the dose escalation group was one case of pneumonia. Table 2 further examines those patients that underwent dose escalation. The median mHBI improved from 9 to 7 following dose escalation. Recaptured clinical response occurred at a rate of 6/11 (55%) based on clinical documentation and 3/11 (27%) based on mHBI.

CONCLUSION:
UST dose escalation from 90 mg every 8 wks to either every 4 or 6 wk dosing allowed for recaptured clinical response in ∼25-50% of CD patients. There were minimal adverse events in patients who were dose escalated. Given its safety profile, dose escalation should be considered in patients with moderate to severe CD who have incomplete response to UST.