bluuebunny/crossref_metadata_2025_split huggingface dataset:
P007 Treatment of IBD with proton pump inhibitors: Implications for periodontal disease
Authors: Lisa Yerke , Michael Levine , Robert Cohen 
Published: July 2019

BACKGROUND:
Previous studies have shown that an increased risk of complications from Crohn's disease and ulcerative colitis (IBD) is associated with the use of proton pump inhibitors (PPI). PPI can reduce the clinical manifestations of gastrointestinal reflux disease, but also may affect the gastrointestinal and oral microbiota as well as influence bone metabolism. IBD has been positively associated with an inflammatory host response following bacterial infection characteristic of periodontal disease (PD). Consequently, we hypothesized that the severity of PD might be related to the use of PPI. Such a relationship in a patient taking PPI might affect treatment decisions related to both IBD and periodontitis.

METHODS:
This retrospective study was reviewed and approved by the State University of New York at Buffalo (SUNYAB) Institutional Review Board. To test our hypothesis, we examined medical and dental history records of patients aged ≥35 years old that were referred to the SUNYAB School of Dental Medicine postgraduate periodontics program for periodontal evaluation from 2010 to 2017 (N = 1,017). From that group, patients diagnosed with generalized, chronic, moderate-to-severe periodontitis were used in this study (N = 581). To measure PD severity, we calculated the number of teeth with periodontal pocket depths ≥6 mm for each patient. Use of PPI medications was confirmed by review of patient medical records. Populations were adjusted for smoking and diabetes. Significance was measured via computation of the 95% confidence interval and P-value of the difference between the means of each group using IBM SPSS Statistics v25.

RESULTS:
We found that there was an inverse relationship between use of PPI and severity of PD. Specifically, 15.7% of teeth from PD patients taking PPI had periodontal pocket depths ≥6 mm, vs 22.6% of teeth in PD patients not taking PPI (mean difference, 6.9%, 30.5% decrease; 95% confidence interval, 2.2%–11.5%; P = 0.004). After adjusting for diabetes and smoking, this relationship persisted: The prevalence of pocket depths ≥6 was 12.7% in PD patients taking PPI, vs 19.7% for PD patients not taking PPI (mean difference, 7.0%; 35.5% decrease; 95% confidence interval, 3.0%–11.0%; P = 0.0008).

CONCLUSION(S):
In patients with chronic, generalized, moderate-to-severe periodontitis, our results suggest that use of PPI is associated with smaller periodontal pocket depths, implying less severe PD. The data indicate that more conservative periodontal therapy might initially be considered for IBD patients with advanced periodontal disease for whom PPI are prescribed as a component of their IBD treatment. Prospective studies currently are being developed to determine if PPI can directly modify the course of PD, or if the association between PPI and PD is related to immunologic or microbiologic factors associated with IBD. This study was supported in part by the W.M. Feagans Endowed Chair Fund, and the Department of Periodontics and Endodontics, SUNY Buffalo.
P009 A comparison of pediatric vs adult onset IBD in Puerto Rican Hispanics
Authors: Karelys Burgos , Anna Blanco , Natalie Emanuelli , Esther Torres 
Published: July 2019

BACKGROUND:
The IBD Registry collects demographic and medical information of patients with confirmed ulcerative colitis (UC) and Crohn's disease (CD). The 4-fold increase in IBD in Puerto Rico including children warrants exploration of this population. The aim is to describe clinical features of IBD in pediatric vs adult onset Puerto Ricans.

METHODS:
This is a cross-sectional study in where registry entries from 1995 to 2018 were analyzed for demographics, medical information, family history, extra-intestinal manifestations, surgery, duration of disease and interval between symptom onset and diagnosis using ANOVA. Data was divided into pediatric onset (age of onset ≤18 years old), and adult onset IBD (≥19 years old), then each group was subdivided by disease, CD and UC. The IBD Registry is approved by the Medical Sciences Campus IRB.

RESULTS:
Nine hundred Seven Puerto Ricans with IBD, 541 (59.7%) with CD and 366 (40.3%) with UC, were included. Three hundred fifty-five (39.1%) were pediatric onset and 552 (60.9%) adult onset IBD. Mean age of onset was 31.6 ± 11.6 in adult onset and 14.1 ± 3.8 in pediatric onset patients. Two hundred ninety-five patients had at least one extra-intestinal manifestation, 40.5% in the adult onset and 20% in the pediatric onset group. Arthritis was the most common extra-intestinal manifestation in both groups. Family history of IBD was present in 33.5% and 18.7% of pediatric and adult onset, respectively (P = 0.2). Pediatric onset subjects had a higher prevalence of remote relatives with IBD (21.3% vs 13.2% of the adults, P < 0.05). 71.4% of the adult onset IBD patients and 36.6% of the pediatric had ≤5 years with disease. Interval less than 1 year between onset of symptoms and diagnosis in the pediatric group was 55% for UC and 45.1% for CD. For the adult group, 64.2% and 51.5% of UC and CD respectively were diagnosed within a year. Prevalence of surgery was 30.9% and 55.8% for all UC and CD respectively (P = 0.002); and 47.3% for pediatric and 44.7% for adults (P = 0.6).

CONCLUSION(S):
Significant differences between pediatric and adult onset Puerto Ricans with IBD were a higher prevalence of EIM in adults and a higher proportion of non-first-degree relatives with IBD in pediatrics. As expected, the prevalence of surgery was higher in patients with CD than in patients with UC in both groups. The majority of patients had 5 years or less of disease and were diagnosed within 1 year of the onset of symptoms. This study contributes to a better understanding of the epidemiology of IBD in Puerto Rican Hispanics.
P010 Results from a new anti-vedolizumab antibody assay
Authors: Maria Rosario , Lili Yang , Timothy Wyant 
Published: July 2019

BACKGROUND:
Immunogenicity was assessed in GEMINI I (NCT00783718) and II (NCT00783692) using an enzyme-linked immunosorbent assay (ELISA).
1,2
It was later determined that the presence of ∼0.5 μg/mL of vedolizumab interferes with the ELISA, which potentially might have underestimated on-drug immunogenicity. Therefore, a new acid dissociation electrochemiluminescence (ECL) anti-vedolizumab antibody (AVA) assay was developed with a drug tolerance of ≥50 μg/mL. In addition, a more drug-tolerant ECL assay was developed to quantify the ability of AVAs to neutralize vedolizumab (neutralizing assay). The current study reassessed vedolizumab immunogenicity using banked serum samples from GEMINI I and II with the ECL assays.

METHODS:
Positive or negative AVA status was determined according to the previous ELISA assay definitions, and overall AVA positivity was summarized using descriptive statistics. The effect of AVA on vedolizumab pharmacokinetics (PK) was assessed using a previously reported population PK model 1 that was updated with data from the ECL assay. Serum samples from 1,427 of 1,434 patients who received continuous treatment with vedolizumab for 52 weeks were available for reanalyses. Samples confirmed as AVA positive were further characterized using the neutralizing assay.

RESULTS:
With the ECL assay, 6% (86/1,427) of patients were AVA positive at any time during the study. Of these, 20 patients were considered persistently positive (confirmed AVA positive in ≥2 consecutive AVA samples) and 56 had neutralizing antibodies. With the ELISA, 4% (56/1,434) of patients were AVA positive at any time. Of these, 9 patients were considered persistently positive and 33 had neutralizing antibodies.
2
Parameter estimates, precision of PK structural parameters, interindividual and residual variabilities, and covariate effects (including AVA effects) were comparable between the previous and updated final population PK models. Therefore, inferences regarding the clinical relevance of covariates were also similar between the 2 PK models. In the updated PK model, AVA presence was estimated to increase vedolizumab linear clearance (CLL) by a factor of 1.10 (95% credible interval [CDI]: 1.03, 1.17), consistent with the previous final model where AVA was estimated to increase CLL by a factor of 1.12 (95% CDI: 1.05, 1.2). With the ECL assay, of the 61 patients who had an adverse event assessed by the investigator as an infusion-related reaction, 6 (10%) were AVA positive, 2 of whom were persistently positive. With the prior ELISA, 3 of 61 (5%) patients were AVA positive, all 3 of whom were persistently positive.
2

CONCLUSION(S):
Vedolizumab immunogenicity rates and PK were similar between the ECL and ELISA assays. Compared to the ELISA assay, the ECL assay detected slightly more AVA-positive patients among patients with infusion reactions.
P013 Fecal calprotectin predicts relapse in UC patients with histological remission
Authors: Sung Jung , Bum Kim Dae , Kang-Moon Lee , Min Lee Ji 
Published: July 2019

BACKGROUND:
Histological remission has been recognized as the treatment goal of ulcerative colitis (UC). We aim to investigate the factors that predict relapse in UC patients with histological remission.

METHODS:
We performed a prospective study of patients with UC from March 2014 to February 2016. If patients have mucosal healing during endoscopy, several biopsy specimens were collected from sigmoid colon and rectum. An expert pathologist evaluated colonic biopsies for histological activity (Geboes score). Histological remission was defined as a Geboes score <3.1. Demographic data, serological data including hemoglobin, hematocrit, white blood cell and platelet counts, albumin, C-reactive protein, and fecal calprotectin (FC) within a week of endoscopy were collected.

RESULTS:
Of the 36 patients in histological remission, 9/36 (25%) relapsed after a median follow-up of 29 months (range 2-45 months). FC was significantly higher in patients who relapsed compared with patients who maintained clinical remission (153.7 μg/g vs 103.4 μg/g; p = 0.047). In multivariate analysis, the FC was only independent predictors of relapse. A receiver operating characteristic analysis estimated a cutoff level of >134.6 μg/g for FC (area under the curve, 0.758 and confidence interval 95%, 0.579–0.937) for predicting relapse during follow-up with 77.8% sensitivity, 74.1% specificity.

CONCLUSION(S):
High FC levels can predict relapse in patients with UC. Therefore, regular measurement of FC should be considered in UC patients, even if they have histological remission.
P016 Lipidomics in ulcerative colitis reveal disruption of mucosal lipid composition associated with the disease state
Authors: Joseph Diab , Rasmus Goll , Terkel Hansen , Einar Jensen , Thomas Moritz , Jon Florholmen , Guro Forsdahl 
Published: July 2019

BACKGROUND:
Several genetic, bacterial, and environmental factors appear to lead to the onset of ulcerative colitis (UC). Moreover, UC seems to be associated with alterations in lipid metabolism, and a disruption of the balance between pro and anti-inflammatory molecules. Membrane bioactive lipids modulate the immune response by functioning as intra- and intercellular signaling molecules. However, there are only few studies describing the mucosal lipid bio-signatures during IBD. Therefore, our study aims to characterize mucosal lipid profiles in treatment-naive UC patients and deep remission UC patients, compared to healthy subjects.

METHODS:
Newly diagnosed treatment-naive UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission demonstrated by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified and included for data analysis.

RESULTS:
Sixteen lipids showed significant concentration differences between the study groups reflecting the inflammatory state. The majority of significantly up- or down- regulated lipids were phosphatidylethanolamines (PE), and ceramides (Cer). Data analysis revealed that changes in Cer18:1/24:1, Cer18:1/24:0, and PE38:3 were most prominent between the groups. The concentration of Cer18:1/24:1 was highly increased in UC patients' inflamed mucosa compared with UC patients' healed mucosa, whereas, PE38:3 is exclusively present in UC patients' colonic mucosa (both treatment naive and remission state patients). Furthermore, Cer18:1/24:0 was elevated in a stepwise manner from control to remission, and active UC.

CONCLUSION(S):
Lipid analysis in UC revealed alterations in the mucosal lipid composition. In this study, we report several lipids, which might be involved in the inflammatory response and pathogenesis seen in IBD. The PE38:3 is especially interesting in a pathophysiological context since it is found in both active colitis and deep remission but not healthy controls.
P017 Cost burden of CD and UC is significantly higher up to 10 years before diagnosis: A Danish register-based study
Authors: Kasper Vadstrup , Sarah Alulis , Andras Borsi , Tine Jørgensen , Nina Gustafsson , Sandra Stallknecht , Niels Qvist , Pia Munkholm 
Published: July 2019

BACKGROUND:
Population-based data on the economic burden of Crohn's disease (CD) and ulcerative colitis (UC) is limited and the burden prior to diagnosis has not yet been reported. This study estimates the ten-year societal costs prior to the diagnoses of CD and UC patients and the 5-year attributable costs after diagnosis in a national patient cohort from Denmark.

METHODS:
In this register study using the Danish National Patient Register and the Danish longitudinal database on employment (the DREAM database), incident CD and UC patients between 2002–2016 were assessed and matched on age and gender with one non-diseased control. Ten-year average annual costs were calculated for cases and controls prior to diagnosis. Five-year attributable costs after the date of diagnosis were also estimated using a difference-in-difference approach. Costs included health care services, prescription medicine, home care services and production loss. Odds ratios for the occurrence of diseases requiring a hospital contact before diagnosis were estimated using logistic regression analyses.

RESULTS:
The study included 10,302 incident CD and 22,144 incident UC patients. Average costs were significantly higher for CD/UC patients than controls throughout the ten-year period prior to diagnosis. The difference increased over time and equaled €3,377 for CD and €2,960 for UC patients in the year before diagnosis. CD/UC patients had significantly more hospital contacts than controls prior to inflammatory bowel disease (IBD) diagnosis, with 51.6% of CD patients and 52.4% of UC patients having other diagnoses related to the digestive system. The average attributable costs were highest the first year after diagnosis, equalling €12,919 per CD patient and €6,501 per UC patient. Hospital admission costs accounted for 36% for CD and 31% for UC patients—prescription medicine for 3% and 7%, respectively.

CONCLUSION(S):
This study provides population-based evidence of the substantial economic burden of CD and UC 10 years prior to and 5 years after diagnosis. These findings may indicate a significant diagnostic delay of CD and UC and warrants more research into the possible causes.
P018 Hypersensitivity reactions to intravenous iron are rare in clinical practice
Authors: Oskar Frigstad Svein , Monirul Islam Md 
Published: July 2019

BACKGROUND:
In inflammatory bowel disease (IBD), iron deficiency anemia is the most common systemic complication, and has been reported in 20%–42% of patients, while iron deficiency has been reported in 35-90% of patients. Intravenous iron allows for efficient and well-tolerated treatment in iron deficiency and is routinely used in IBD. Infusion reactions are in clinical studies reported in 1%–3% of iron infusions. The pathogenesis of these infusion reactions is not fully known but complement-activated pseudoallergy seems to be the most important mechanism. The aim of this study was to investigate the safety of iron isomaltoside in clinical practice.

METHODS:
We have performed a prospective registration of all infusion reactions and reports of delayed hypersensitivity following infusions of iron isomaltoside in our hospital from November 2012 to June 2018. The simplified dosing regimen was recommended, and 1,000 mg was used as the defined daily dose in the data analyses. The study was performed as a quality assessement project and was approved by the Regional Data Protection Official. Clinical and epidemiological data were registered, as well as study drug characteristics, dosing, type of hypersensitivity and outcome variables. All hypersensitivity reactions were reported to the health authorities.

RESULTS:
We estimated that a total of 1,240 infusions equivalent to 1,000 mg of iron isomaltoside were given. Acute infusion reactions were reported in 2% (29/1,240) of infusions and delayed hypersensitivity in 0.5% (6/1,240) of infusions. More female (25/29) than male (4/29) patients had acute infusion reactions (P < 0.05). Three patients got infusion reactions on the second infusion and one patient had infusion reactions on both the second and the third infusion. We found no association between dose given and frequency of infusion reactions. No single batch of study drug associated with more infusion reactions was identified. All patients had uneventful recoveries.

CONCLUSION(S):
In this study hypersensitivity following iron isomaltoside was relatively rare in clinical practice. Infusion reactions are most frequently mild and seem to occur more often in women. No association to dose given was shown.
P021 The potential impact of provider gender on IBD management
Authors: Lindsay Clarke , Nadeem Tabbara , Adam Greenfest , Daniel Szvarca , Sarah Turki , Rahma Aldhaheri , Tina Boortalary , Marie Borum 
Published: July 2019

BACKGROUND:
Health maintenance guidelines have been published to ensure optimal clinical outcomes for individuals with inflammatory bowel disease (IBD), with recommendations including the evaluation of bone density, eye, and skin health. However, it has been suggested that there is variability in adherence to health maintenance recommendations. This study evaluated both the gender of providers discussing health maintenance with patients, and the overall rate of physicians' recommendations for Dual-energy X-ray absorptiometry (DXA) scans, vitamin D levels, ophthalmologic exams, and skin protective measures at an urban university medical center.

METHODS:
A retrospective chart review was performed evaluating all IBD patients seen at a university gastroenterology clinic over a 5-year period was performed. Patients' IBD diagnosis, recommendations for DXA, vitamin D levels, ophthalmologic exams, and skin protective measures (sunscreen and/or dermatology referral) were obtained. Patient and physician gender were recorded. 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 IRB.

RESULTS:
393 IBD patients were identified (175 males, 218 females) with mean age of 44.4 (age range: 20–82). 279 (71.0%) had Ulcerative Colitis (UC), 96 (24.4%) had Crohn's disease (CD), 7 (1.8%) with unspecified colitis, and 11 (2.8%) had microscopic colitis. Of the 393 patients, 279 (71.0%) were seen by male providers and 114 (29.0%) were seen by female providers. 249 (63.4%) patients had vitamin D and 110 (28%) had DXA scans performed. Ophthalmologic referrals were offered to 125 (27.8%). 83 (21.1%) were counseled about skin protective measures and given dermatology referrals. Significantly more female providers recommended vitamin D (P = 0.015), DXA screening (P = 0.027), ophthalmologic evaluations (P < 0.0001) and dermatologic referrals (P < 0.0001) compared to male providers. There was no significant difference of the performance of health maintenance recommendations based upon disease type.

CONCLUSION(S):
This study revealed that there was inconsistent adherence to IBD health maintenance recommendations. While female physicians more frequently recommended vitamin D screening, DXA scans, ophthalmologic examinations, and skin evaluations, there was a clear need to improve screening by all physicians. While this study was limited based upon retrospective design, small sample size, and single institution cohort, it provides a foundation for future research that addresses IBD management. Increased efforts to optimize IBD care will improve overall clinical outcomes.
P023 5-Aminosalicylate intolerance is a risk factor for hospitalization in patients with UC
Authors: Yusuke Yoshimatsu , Shinta Mizuno , Makoto Naganuma , Tomohiro Fukuda , Ena Nomura , Kosuke Yoshida , Satoko Umeda , Keiko Ono , Shinya Sugimoto , Kosaku Nanki , Yohei Mikami , Kayoko Kimura , Makoto Mutaguchi , Tomohisa Sujino , Kaoru Takabayashi , Haruhiko Ogata , Yasushi Iwao , Takanori Kanai 
Published: July 2019

BACKGROUND:
In recent years, a number of therapeutic drug for patients with ulcerative colitis (UC) has been developed. Meanwhile, 5-aminosalicylic acid (5-ASA) has few serious adverse events, and remains as the first-line drug in induction therapy and maintenance therapy for UC. However, 5-ASA often cause diarrhea, fever and skin rash, and it is often difficult to maintain remission in these cases. There are few studies about the effect of 5-ASA intolerance on the prognosis of patients with UC. In this study, we aimed to clarify the optimal treatment strategy for patients with 5-ASA intolerance by examining the 5-ASA intolerance using the IBD registry of our hospital.

METHODS:
A multi-center retrospective cohort study of UC patients, who visited our hospital from January 2015 to June 2018, was performed, and we enrolled 793 UC patients in IBD registry. We collected the detail clinical information of enrolled patients in the prior year, and the primary outcome was hospitalization. Risk factors for hospitalization were assessed by binary logistic regression analysis. This study was approved by the ethics committee of Keio University School of Medicine (approval number: 20160038).

RESULTS:
We defined 5-ASA intolerance as patients who had at least one in the following symptoms due to 5-ASA administration; headache, gastrointestinal symptoms, cutaneous symptoms, and fever. The rates of 5-ASA intolerance were 28.5% (22/77) in admission group and 5.1% (37/716) in no admission group. Our multivariate analysis showed that the following 3 factors have significant correlations with hospitalization; 5-ASA intolerance (odds ratio (OR) = 5.46, 95% confidence interval (CI) = 2.20–13.5), extent of disease (OR = 9.47, 95% CI = 1.25–71.6), and serum albumin level (OR = 0.122, 95% CI = 0.07–0.20). On the other hand, IM intolerance, age, duration of disease, and 5-ASA non-administration were not significantly correlated with hospitalization. Furthermore, compared with 5-ASA tolerance group, the intolerance group had significantly greater incidences of corticosteroid usage (P < 0.001) and calcineurin inhibitor usage (P < 0.01).

CONCLUSION(S):
It became clear for the first time that 5-ASA intolerance is the risk factor for hospitalization and worsen the prognosis of patients with UC. Therefore, even when we encounter patients with UC who are intolerant to one of the 5-ASAs, switching to another 5-ASA and continuing 5-ASA administration under strict observation may improve the prognosis of patients with UC.