bluuebunny/crossref_metadata_2025_split huggingface dataset:
A246 EXAMINING BARRIERS TO PHYSICAL ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS
Authors: Morin S , Byra M , Issenman R , Timmons B , Obeid J 
Published: February 2024

Abstract

Background
Inflammatory bowel disease (IBD) poses significant challenges to pediatric patients, affecting their physical and psychological well-being. Physical activity can be an essential component of managing IBD, yet its adoption among this population remains suboptimal. Understanding the factors that influence physical activity levels in youth with IBD, particularly barriers to engagement, is crucial.

Aims
(1) Describe physical activity levels in pediatric IBD, and (2) assess the relationship between physical activity and barriers to physical activity in youth with IBD.

Methods
We recruited patients between the ages of 7-17 years with a single confirmed diagnosis of IBD. Participants completed a barriers to physical activity questionnaire adapted from Zabinski et al. (2003). Each item was scored on a scale from 1 to 5, to yield a total barriers score and subdomain scores for body-related, convenience, resource, social, fitness, and disease-related barriers; each score presented as an average out of 5. Lower scores indicated lower barrier burden. Participants also wore accelerometers during waking hours for 7 consecutive days to quantify daily average total physical activity (TPA), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Descriptive statistics and multiple regression analyses were used to determine the relationship between physical activity and barriers to physical activity.

Results
Forty-nine youth completed the study (31% females; age: 14.77±1.98 years). Physical activity levels were low (TPA: 146.6±49.5 min/day; LPA: 104.2±33.4 min/day; MVPA: 42.4±21.2 min/day), with only 21% of participants meeting the 24-hour movement guidelines of 60 min/day of MVPA. Total and resource barriers both significantly predicted TPA (total: β=-47.76, p=0.004; resource: β=-48.30, pampersand:003C0.001), LPA (total: β=-29.01, p=0.01; resource: β=-29.68, pampersand:003C0.001), and MVPA (total: β=-18.75, p=0.01; resource: β=-18.62, pampersand:003C0.001). Fitness barriers significantly predicted TPA (β=-41.48, p=0.016) and MVPA (β=-22.01, p=0.008). Body-related, convenience, social, and disease-related barriers did not significantly predict TPA, LPA, or MVPA.

Conclusions
Our findings confirmed that youth with IBD are not engaging in enough physical activity. Importantly, we found those with higher total barrier, resource- and fitness-related barriers presented with 18-48 fewer minutes of daily physical activity. These findings highlight the need for tailored interventions aimed at reducing specific barriers to support physical activity participation in youth with IBD.

Funding Agencies
None
A247 THE IMPACT OF BIOLOGICS ON MATERNAL AND NEONATAL OUTCOMES IN PREGNANT PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND THEIR ASSOCIATION WITH THERAPEUTIC DRUG LEVELS
Authors: Nabavian H , Eisen S , O'Connor K , Srikanth V , Huang V 
Published: February 2024

Abstract

Background
Biologic therapies are at the backbone of managing moderate to severe IBD and maintaining clinical remission. The data on the effects of biologic therapy on maternal and neonatal outcomes continues to be limited. To our knowledge, there have been no previous studies specifically investigating whether biologic therapeutic drug levels in pregnant patients are related to maternal and neonatal outcomes.

Aims
The objective of this study is to determine whether biologic use in pregnancy is associated with adverse maternal and fetal outcomes, and if those outcomes correlate to specific therapeutic drug levels.

Methods
In this study, we retrospectively evaluate patients at a high-volume pregnancy and inflammatory bowel disease centre at Mount Sinai Hospital in Toronto between January 1st, 2017 to December 31st, 2022. Primary outcomes include maternal complications, such as induction of labour, cesarean section, peripartum infections, placental abruption, preterm labour and pre-eclampsia. Secondary outcomes include neonatal complications, such as preterm birth, low birth weight (ampersand:003C2500g), congenital anomalies and the presence of neonatal infection. These outcomes will be compared to therapeutic drug levels measured in preconception, during pregnancy and post-partum.

Results
A total of 312 patients were included in our study, of which 152 were on biologic treatment for IBD. Of the biologics population, the majority of patients are on Remicade, followed by Humira and Stelara (Table 1). Preliminary data analysis reveals that there was no significant difference in the rate of miscarriages (10% vs. 6%, P= 0.1), cesarean section (44% vs. 38%, P=0.3) and preterm deliveries (12% vs. 14%, P=0.7) between the biologics vs. non-biologics patient groups. Next round of analysis will include secondary outcomes and therapeutic drug levels.

Conclusions
Through this study, we hope to add to the literature on the possible safety of maintaining biologic therapy during pregnancy in those with inflammatory bowel disease. The data on proactive therapeutic drug monitoring in pregnant patients may bring to light the importance of its inclusion in clinical decision-making algorithms.
Breakdown of therapies in the biologic patient group

Funding Agencies
None
A248 RISK OF ARRHYTHMIA IN INFLAMMATORY BOWEL DISEASE
Authors: Narous M , Nugent Z , Rabinovich-Nikitin I , Kirshenbaum L , Bernstein C 
Published: February 2024

Abstract

Background
Inflammatory bowel disease (IBD) has been shown to be associated with stroke or early atherosclerosis. Atrial fibrillation (AF), being the most common arrhythmia seen clinically, can be a consequence of systemic inflammation. The association between IBD and arrhythmia has been studied in recent literature with inconclusive evidence.

Aims
1. To determine the risk of arrhythmia (defined as AF, other supraventricular or ventricular tachycardia) in IBD.
2. To compare the risk of arrhythmia amongst IBD medications.
3. To assess mortality in IBD with arrythmia as compared to controls.

Methods
The risk of arrhythmia was determined in a retrospective population-based cohort study using the University of Manitoba IBD Epidemiology Database (11,432 IBD cases and 109,582 matched controls). Arrhythmia risk in IBD was adjusted for presence of comorbidities of the Charlson Comorbidity Index (CCI). The effect of IBD medications on the development of arrhythmia was assessed in a nested case-control study of individuals with IBD. Follow-up started on date of IBD diagnosis until arrhythmia diagnosis, emigration out of the province of Manitoba, death, or March 31, 2018. Cases were censored at date of first database identification of a diagnosis of heart failure or myocardial infarction. All-cause mortality was a secondary outcome compared across non-IBD controls and IBD cases with arrhythmia using proportional hazards regression analysis was done.

Results
Persons diagnosed with IBD were more likely than controls (HR 1.51; 95% CI 1.30-1.76) to develop arrhythmia. When controlling for CCI comorbidities, the significant association between IBD and arrhythmia remains. Medications including 5-ASA, thiopurines, and TNFa inhibitors were not associated with arrhythmia, with OR 0.99 (95% CI, 0.68-1.45), 1.06 (95% CI, 0.57-1.97), and 0.90 (95% CI, 0.31-2.61), respectively. All-cause mortality was slightly increased in persons with IBD in analyses unadjusted and adjusted for the presence of arrhythmia, with HR's of 1.13 (1.07-1.19) and 1.12 (1.06-1.18). Increased mortality was more pronounced in CD, but UC did not raise risk of mortality.

Conclusions
Persons with IBD have a higher risk of arrhythmia even prior to a diagnosis with heart disease. IBD medications did not raise risk of arrhythmia in our dataset. All-cause mortality, with the development arrhythmia as a time dependent variable, was significantly raised in CD as compared to non-IBD controls, but not in UC. Further data are necessary to establish the risk of arrhythmia in IBD, especially with stratification by setting of arrhythmia diagnosis and severity of IBD based on Montreal classification.

Funding Agencies
None
A249 PARADOXICAL PSORIASIS FOLLOWING ANTI-TNFΑ THERAPY IN INFLAMMATORY BOWEL DISEASE AND ASSOCIATION WITH AN IL-23 RECEPTOR VARIANT: A PRELIMINARY REPORT
Authors: Natt N , Wilson A 
Published: February 2024

Abstract

Background
Patients with inflammatory bowel disease (IBD) who receive anti-tumor necrosis factor (TNF) α therapy are at risk of developing drug-related psoriatic skin lesions known as paradoxical psoriasis (PP). This is a severe unpredictable adverse drug event that often leads to discontinuation of anti-TNFα therapy. To date, there are no tools for identifying high-risk individuals. Variation in the IL-23 receptor (IL23R) gene has been linked to psoriasis onset and may be implicated in PP.

Aims
To evaluate the frequency of the IL23R variant (IL23R1142Gampersand:003EA) in anti-TNFα exposed IBD patients who develop PP versus those who do not. Clinical variables associated with PP development will also be assessed.

Methods
A case-control study is ongoing, including anti-TNFα-exposed adult IBD patients. Participants are divided based on the development of PP (cases n=11; controls n=48, identified to date, 500 additional patients will be screened). All participants were retrospectively genotyped for the occurrence of the IL23R1142Gampersand:003EA variant. Clinical variables and outcomes were assessed from the time of anti-TNFα exposure for at least one year of follow-up or to the time of anti-TNFα discontinuation.

Results
To date, we have included 59 adult IBD patients treated with infliximab or adalimumab. Eleven patients developed PP after a median duration of treatment of three months with anti-TNFα therapy. The most common presentations were guttate, plaque, and pustular psoriasis. Six patients had PP that involved 50% or more of their body surface area (BSA). Nine participants discontinued their anti-TNFα therapy due to PP. None of the cases had a personal or family history of psoriasis. PP patients were similar to controls with respect to age, sex, ethnicity, IBD type, disease duration, and concurrent immunomodulator use. The variant genotype occurred more frequently in PP patients compared to controls (54.5% vs. 4.2%, OR 27.6, 95%CI 4.3-145.4). Those with the variant genotype also had more extensive psoriasis compared to wildtypes (mean BSA 61% vs. 25%, p=0.045).

Conclusions
In this preliminary analysis, there was an increased frequency of the IL23R1142Gampersand:003EA variant in patients who developed PP compared to those who did not after anti-TNFα exposure. We did not identify any other clinical variables associated with development of PP. Interpretation of these results is limited by the small sample size. Completion of this study may help clarify the association between PP and the IL23R gene as well as other clinical risk factors implicated in PP development.

Funding Agencies
None
A250 CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE
Authors: O'Brien E M , Potdar C , Mulder D 
Published: February 2024

Abstract

Background
Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity.

Aims
To characterize the changes to MIP1a production and localization in response to disease activity in IBD.

Methods
Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4).

Results
An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort.

Conclusions
With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity.

Funding Agencies
CIHR
A252 DRUG DISCONTINUATION AND PERSISTENT SYMPTOMS AMONG THE USERS OF BIOSIMILAR AND LEGACY ANTI-TNF DRUGS IN A REAL-WORLD CANADIAN IBD COHORT
Authors: Oketola B , Lukusa L , Birck M , Neville A , Leung Y , Narula N , Afif W , Bernatsky S , Singh H 
Published: February 2024

Abstract

Background
Biosimilars and their reference originator drugs are increasingly used for inducing and maintaining remission in Inflammatory Bowel Diseases (IBD). Persistent symptoms, such as fatigue and joint pain, have been reported among individuals with IBD in remission. However, there is limited data on the persistence of symptoms among long-term users of biological therapy.

Aims
We report on drug discontinuation and persistent symptoms among a multicentre cohort of IBD patients 12 months after initiating anti-TNF originators or biosimilars.

Methods
We enrolled and followed individuals with IBD (ampersand:003E18 years) who initiated therapy with infliximab or adalimumab, bio-originators/biosimilars, between January 2019 and March 2023. We determined the rate of discontinuation of therapy, persistent symptoms, and quality of life (QoL) after 12 months. Difference in effect estimates (proportions and means) between the two groups (originators versus biosimilars) was determined.

Results
181 individuals with IBD (CD = 58%, female = 46%, Caucasian = 85%) were enrolled. 62% were biologic-naïve at initiation. Of the 119 participants who completed a 12-month follow-up visit, about 19% (n = 34) discontinued drug use (all were infliximab users). Insufficient disease control was the most common reason for drug discontinuation (18.2%, n = 33). There was a significant reduction in the number of corticosteroid users at follow-up in both originator (rate ratio: 0.33, 95% confidence interval (CI): 0.16-0.49) and biosimilar users (rate ratio: 0.22, 95% CI: 0.14-0.30). With our limited power, we were unable to detect significant reductions in ER visits and hospitalizations in the first year after initiation of anti-TNF agents compared to that in the preceding year. The severity of pain/discomfort anywhere and the frequency of fatigue and anxiety/depression was not significantly reduced at 12 months in either of the groups. The percentage of those reporting moderate/severe abdominal pain was reduced among biosimilar users (46% to 20%; rate ratio of 0.26, 95% CI: 0.15-0.38), and originator users (28% to 13%, rate ratio 0.16, 95% CI: -0.02, 0.33). The proportion of those reporting rectal urgency at least some of the time was also reduced among both originators (30% at baseline to 9% at follow-up) and biosimilar users (33% to 17%). There was a significant improvement in QoL scores among both originator users (mean difference (MD) 13.0, 95% CI: 6.00-22.0) and biosimilar users (MD 10.0, 95% CI: 6.00-14.0) on the SIBDQ. This improvement was replicated on the EQ-5D only among biosimilar users.

Conclusions
Our study results suggest that even though the use of anti-TNF drugs leads to improvement in QoL, there may be no reduction in some symptoms, such as fatigue, anxiety, depression.

Funding Agencies
CIHR
A262 THE EXCESS USE OF PROTON-PUMP INHIBITORS IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
Authors: Singh N , Nugent Z , El-Matary W , Singh H , Shaffer S , Bernstein C 
Published: February 2024

Abstract

Background
Proton-pump inhibitors (PPI) use can impact the gut microbiome, thus, it is possible that use in children may be associated with an increase in pediatric IBD.

Aims
We investigated the common gastrointestinal symptoms that result in a PPI prescription in pediatrics prior to a diagnosis of IBD and the degree to which children with IBD use excess PPIs compared to controls either prior to or post a diagnosis of IBD.

Methods
The University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD 1984-2018 with age, sex, and geographic-matched controls. PPI prescription data were assessed from April 1995 onwards in children diagnosed with IBD prior to age 18.

Results
PPI were dispensed prior to IBD diagnosis in 9% of 614 children diagnosed with IBD and 0.8% of 5718 controls (P ampersand:003C0.0001) with the median age being 15 years. Children with Crohn’s disease were no more likely to have been PPI-users pre-diagnosis (10%) than persons with ulcerative colitis (8%, p=0.57). Relative PPI use increases within 1-year of an IBD diagnosis (rate ratio, RR=22.4 (95% CI 13.6-37); P ampersand:003C 0.001) compared with 3-5 years pre-IBD (RR=4.9, 95% CI 1.4-16.7) and 1-3-year pre-IBD (RR=2.5, 95% CI 1.01-6.2). The percent of children being prescribed a PPI increased the more they visited a physician, which was associated with increased likelihood of being prescribed a PPI. PPI use was similar for the various gastrointestinal diagnoses in cases of IBD and controls. PPI users prior to a diagnosis may have less severe disease than non-PPI users. We found they were less likely to be hospitalized (HR 0.36, 95% CI 0.19 – 0.68; P = 0.002). There was no difference among children who had surgery for their IBD whether they were PPI users prior to IBD diagnosis compared to non-users.

Conclusions
PPI use was commonly prescribed for a variety of gastrointestinal complaints, similarly in cases and controls. Children with IBD have many more contacts for gastrointestinal diagnoses than controls even for 5 years prior to their diagnosis. This raises the possibility that PPIs are prescribed indiscriminately for gastrointestinal complaints since their use was not restricted to complaints warranting PPI use, or that PPIs are prescribed for early symptoms that are secondary to IBD.

Funding Agencies
None
A264 IDENTIFYING CLINICAL PREDICTORS FOR SUCCESS OF EXCLUSIVE ENTERAL NUTRITION INDUCTION THERAPY IN PEDIATRIC CROHN DISEASE
Authors: Suarez Suarez R G , McClement D G , Huynh H , Griffiths A , Shaikh A , Otley A , Jacobson K , Sherlock M , Mack D , Deslandres C , El-Matary W , deBruyn J , Walters T , Wine E 
Published: February 2024

Abstract

Background
Current treatments for IBD focus on reducing inflammation, mostly through suppression of the immune system. Exclusive enteral nutrition (EEN) is recognized as the first line therapy for mild-to-moderate luminal pediatric Crohn disease patients pCD. Although EEN is safe, as it does not suppress the immune system, it poses considerable challenges to patients, mostly due to palatability and monotony of the formula and treatment costs. Moreover, the efficacy of EEN varies greatly from patient to patient. Therefore, there is a need to distinguish between responders and non-responder patients.

Aims
Identify clinical features associated with efficacy of EEN induction therapy and apply machine learning to build a classifier to identify EEN non-responders.

Methods
The Canadian Children Inflammatory Bowel Disease Network prospectively enrolled and followed new onset pediatric IBD cases. Prospective data for 308 pCD with EEN as their first treatment for CD are available. Patients with weighted Pediatric CD Activity Indexes (wPCDAI) collected after at least 4 weeks on EEN were compiled into a dataset (n=108). For this analysis, treatment response was defined as a wPCDAI reduction of at least 12.5 points of a patient’s wPCDAI baseline score.
The dataset includes 26 features for each of the 108 pCD patients at time of diagnosis. This included blood test results (Hgb, ESR, CRP, Alb, Htc, Plt), Paris Classifications, height, and weight Z-scores, as well as wPCDAI, SES-CD (simple endoscopic score, CD), PGA (physician global assessment), and Mayo scores.
Odds ratios were calculated to determine whether any features were associated with response to EEN induction therapy. Then, the most relevant features were identified with regularization techniques and a machine learning classifier for predicting response to EEN was built.

Results
Results showed that the appropriate subset of features to include for optimal accuracy over model simplicity are n=4 (PUCAI, PGA, SES-CD scores, and hematocrit). Also, an increase in PGA score (e.g., moving from “mild disease” to “moderate disease”) was associated with an increase in the chance of EEN failure (OR 3.1, 95% CI [1.7,5.8], p=0.0001). The best classifier for predicting EEN response was a random forest consisting of 20 decision trees. The classifier achieved an area under the ROC curve of 0.75 ± 0.07

Conclusions
Our results suggest that it is possible to produce a classifier capable of predicting EEN clinical remission with an accuracy over 60%. Higher PGA, PUCAI, and SES-CD scores show potential for predicting patients less likely to respond to EEN induction. This research has the potential to provide better quality of life for children who live with IBD.

Funding Agencies
CIHRIMAGINE SPOR Network , Women and Children's Health Research Institute