bluuebunny/crossref_metadata_2025_split huggingface dataset:
A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD
Authors: Defaye M , Abdullah N , Iftinca M , Altier C 
Published: March 2021

Abstract

Background
Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown.

Aims
To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain.

Methods
We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation.

Results
Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation.

Conclusions
Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients.

Funding Agencies
CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship
A55 INVESTIGATING THE ROLE OF ENDOGENOUS INTERLEUKIN-10 IN INTESTINAL EPITHELIAL CELLS AND HOMEOSTASIS
Authors: Nguyen H D , Stadnyk A 
Published: March 2021

Abstract

Background
IL-10 is appreciated for its potent anti-inflammatory effects on leukocytes in mucosal immunity. However, far less attention has been paid to the impact of IL-10 on epithelial cells, which make up the crucial barrier interface between the host mucosa and the external environment. Furthermore, most studies examine the effects of exogenous IL-10, disregarding the possible presence and function of autocrine or paracrine IL-10 in the epithelium.

Aims
Using ex vivo organoids we aimed to examine the small intestinal epithelium for IL-10 and dissect any role for endogenously produced cytokine.

Methods
We growed small intestinal organoids (enteroids) from crypts isolated from C57BL/6 mice (WT) and IL-10-gene knockout mice (IL-10KO). Cellular markers were characterized through qpCR, while IL-10 and IL-10 receptor localization was characterized though immunofluorescence.

Results
We discovered that cells in WT enteroids expressed IL-10 and IL-10R1 constitutively throughout development. Immunofluorescent staining revealed that IL-10 localizes to Paneth cells and appears to be secreted apically. Having established that IL-10 is secreted in enteroids, we compared enteroids from IL-10KO versus WT mice. IL-10KO enteroids developed to morphologically resemble WT enteroids; however, we detected an imbalance with lower secretory cell markers over absorptive cell types in the IL-10KO enteroids, measured as less mRNA for lysozyme, cryptdins and mucin-2. Addition of IL-10 to IL-10KO enteroids did not correct these defects, but did ameliorate the lineage balance by reducing absorptive cell lineage markers (sucrose isomaltase). IL-10R1 was localized on both apical and basolateral side of cell in enteroids. We suspect that epithelial-derived IL-10 likely acts on apical IL-10R, which may conduct a different response from basolateral receptor stimulation.

Conclusions
In conclusion, IL-10 is present in the small intestinal epithelium; more remains to be determined regarding the role this cytokine plays in gut development and homeostasis.

Funding Agencies
NSERC
A78 THE IMPACT OFGASTROINTESTINAL FOLLOW UP CARE ON HEALTHCARE UTILIZATION IN PATIENTS WITH ESINOPHILICESOPHAGITID (EOE).
Authors: Alazemi K , Alkhattabi M , Gregor J C 
Published: March 2021

Abstract

Background
EOE is an increasingly recognized gastrointestinal condition that causes significant morbidity ranging from dietary limitations to food impactions requiring emergency room visits. There are a variety of dietary, pharmacologic and endoscopic treatments available but most are more practically guided by a subspecialist familiar and experienced with the condition. There is a perception among some physicians that follow up is sporadic and may be related at least in part to patient compliance.

Aims
To assess the true rate of EOE patients follow up rate at Lodon Health Scince Center

Methods
We used a retrospective cohort of patients diagnosed with EoE between July 2011 and June 2014 who met the traditional diagnostic criteria. As part of a quality improvement initiative, local follow up over the ensuing 5–7 years was tracked. The impact of follow up on subsequent healthcare utilization was analyzed.

Results
123 patients with biopsy confirmed EoE were analyzed. Follow up appointments were made for 114/123 (92%) patients. 55/123 (45%) had repeat elective endoscopy booked. Only 10/114 (8.7%) of initial appointments went unattended but 15/55 (27.2%) of the patients offered ongoing follow up failed to attend. There were no complications (ie. perforation or bleeding) attributable to any of the procedures. 5/123 (4%) patients required repeat emergency room endoscopy for food impaction. Two patients required this on multiple occasions. 4/5 patients requiring repeat emergency room endoscopy for food impaction had received some sort of follow up, although 4/5 of these had at least one missed appointment. 2/5 patients having emergency room endoscopy required overnight admission. There were no perforations in the cohort.

Conclusions
Patients with a confirmed diagnosis of EOE do have a risk of requiring subsequent emergency endoscopy for food impaction although it is not clear that scheduled follow up significantly reduces that risk. Contrary to the perception of some physicians, patients with EoE are very likely to attend their first follow up visit although the attrition rate for subsequent scheduled visits is not insignificant.

Funding Agencies
None
A79 PROVINCIAL DATA IN ALBERTA REVEAL A CLEAR NEED TO ADDRESS OVERPRESCRIBING OF PROTON PUMP INHIBITORS
Authors: Veldhuyzen Van Zanten S , Jelinski S , Kaplan G G , Reeb L , Morrin L , pow j , McLarty j , Metha A , Novak K L , Burak K W , Greenaway m 
Published: March 2021

Abstract

Background
Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in Canada. They are effective for several upper GI-disorders, have a very favorable safety profile and therefore there are few barriers to prescribing. Concern about overuse of PPIs has been growing. Many patients do not need long term treatment. Patients starting PPI should receive short term therapy (e.g. 8 weeks) and if they respond the need for long term therapy needs to be determined. The usual starting dose is once a day for most indications. Evidence suggests a lack of ongoing indication for PPI in 40–55% of primary care patients.There are economic implications of overuse of PPIs. Public drug spending on PPIs in Canada totaled $288.3 million of $13.5 billion spent in 2017.

Aims
To analyze prescribing data for all PPI prescriptions in Alberta for the years 2017–18 and 2018–19 and 2019–2020, to document number of prescriptions &gt;60 days, the number of new versus repeat prescriptions, proportion of new prescriptions at a greater than 1x daily dose, the proportion of prescriptions written by primary care physicians and to estimate the number of prescriptions targetted for deprescribing.

Methods
Data were obtained anonymously from the Pharmaceutical Information Network (PIN) database from community based pharmacies in Alberta. PPIs were identified using DIN numbers. Prescribed dose and duration were obtained, as well as data on repeat prescriptions. The number of prescriptions that could be targeted for deprescribing was also estimated.

Results
The results are shown in table 1. More than 10% of the population receives a prescription each year. Of these 25–31% were new prescriptions and 69–75% were refills. The percentage of patients who were prescribed PPIs for more than 60 days was 26–28%. Furthermore, 23% of all prescriptions had a defined daily dosage greater than the recommended standard dose of once a day therapy for most indications.75% of all prescriptions are written by family physicians.

Conclusions
Prescription rates of PPIs are very high in Alberta and 75% of patients are on longer term therapy. There likely is significant overprescribing of PPIs, estimated to be up to 40% of patients filling PPI prescriptions in Alberta. This represents a significant avoidable medication and system burden and patient costs. The starting dose of new prescriptions is also high, despite the fact that for most indications the daily dose should be 1x a day. A 20% reduction in prescribing would save at least $ 9 million in Alberta. A deprescribing project has been initiated by the Digestive Health Strategic Clinical Network, a multi-stakeholder network, which addresses important GI issues in Alberta.

Funding Agencies
None
A83 IMPACT OF TELEHEALTH ON MEDICATION ADHERENCE IN GASTROENTEROLOGY CHRONIC DISEASE MANAGEMENT
Authors: Kim H , Tomaszewski M , Zhao B , Lam E , Enns R A , Bressler B , Moosavi S 
Published: March 2021

Abstract

Background
With the COVID-19 pandemic, the demand and availability of telehealth in outpatient care has increased. Although use of telehealth has been studied and validated for various medical specialties, relatively few studies have looked at its role in gastroenterology despite burden of chronic diseases such as inflammatory bowel disease (IBD).

Aims
To assess effectiveness of telehealth medicine in gastroenterology by comparing medication adherence rate for patients seen with telehealth and traditional in-person appointment for various GI conditions.

Methods
Retrospective chart analysis of patients seen in outpatient gastroenterology clinic was performed to identify patients who were given prescription to fill either through telehealth or in-person appointment. By using provincial pharmacy database, we determined the prescription fill rate.

Results
A total of 241 patients were identified who were provided prescriptions during visit with their gastroenterologists. 128 patients were seen through in-person visit during pre-pandemic period. 113 patients were seen through telehealth appointment during COVID pandemic.
The mean age of patients in telehealth cohort was 42 years (57% male). On average patients had 10 prior visits with their gastroenterologists before index appointment, used for adherence assessment. 92% of patients were seen in follow-up, while 8% were seen in initial consultation. The majority of the patients in the telehealth cohort had IBD (89%), while the remaining 11% had various diagnoses, including functional GI disorder, gastroesophageal reflux disease, viral hepatitis, or hepatobiliary disorders. Biologic therapy was the most commonly prescribed medication (66.4%). 45 patients were provided either new medication or dose change, and 68 patients had prescription refill to continue their current medications. It took a mean of 18 days (SD = 16.2) for patients to fill their prescriptions.
Prescription fill rate for patients seen through telehealth and in-person visit were 98.2% and 89.1% (P = 0.004) respectively. Patients seen through telehealth were 6.8 times more likely to fill their prescriptions compared to the in-person counterparts (OR 6.82, CI 1.51 – 30.68, P = 0.004). When we compared adherence rate while excluding biologic therapies, the prescription fill rate was 94.7% in telehealth group and 81.4% in in-person group (OR 4.11, CI 0.88 – 19.27, P = 0.056). Due to high level of adherence, statistical analysis comparing adherent and non-adherent groups was performed but yielded insignificant results.

Conclusions
Medication adherence rate for patients seen through telehealth was higher compared to patients seen through in-patient visit in this study. Telehealth is a viable alternative for outpatient care especially for patients with chronic GI conditions such as IBD.

Funding Agencies
None
A89 CHARACTERISTICS AND CONFLICTS OF INTEREST AT FOOD AND DRUG ADMINISTRATION GASTROINTESTINAL DRUG ADVISORY COMMITTEE MEETINGS
Authors: Khan R , Elsolh K , Gimpaya N , Scaffidi M A , Bansal R , Grover S C 
Published: March 2021

Abstract

Background
The United States Food and Drug Administration (FDA) Gastrointestinal Drug Advisory Committee (GIDAC) is involved in gastrointestinal drug application reviews. Characteristics and conflicts of interest (COI) in GIDAC meetings are not well described.

Aims
To analyze FDA GIDAC meetings and characteristics that predict recommendations.

Methods
This was a cross-sectional study of all publicly available GIDAC meetings where proposed medications were voted on from 1998–2018. Data were collected on individual meetings and individual voting members at meetings. Predefined predictor variables included type of medication, medication sponsor, primary efficacy studies, and voting member characteristics (e.g. committee membership, COI). Univariate analyses were conducted at per-meeting and per-vote levels to assess for predictors of committee recommendation and individual votes respectively.

Results
Thirty-four meetings with 476 individual votes from 1998–2018 were included. Twenty-three (68%) proposals were recommended for approval and 25 (74%) received FDA approval. Most proposals involved &gt;1 primary study (n=27, 79%). At least one voting member had a COI in 24 (71%) of 34 meetings. Twelve (35%) meetings had at least one sponsor COI. Among 476 individual votes, 74 (15.5%) involved a COI, with 33 (6.9%) sponsor COI. COI decreased significantly over time, with more COI in 1996–2000 and 2001–2005 compared to 2006–2010, 2011–2015, and 2016–2020 (p&lt;0.01). There were no significant associations between pre-defined predictors, including COI, and committee level recommendations or individual votes (p&gt;0.05 for all univariate analyses).

Conclusions
The GIDAC reviewed 34 proposals from 1998–2018. The majority were recommended for approval and later approved by the FDA, highlighting the GIDAC’s prominence in the regulatory process. COI are present among GIDAC panelists but decreasing over time and not associated with recommendations.

Funding Agencies
None
A97 TOOLS FOR DIRECT OBSERVATION AND ASSESSMENT OF COLONOSCOPY: A SYSTEMATIC REVIEW OF VALIDITY EVIDENCE
Authors: Khan R , Zheng E , Wani S B , Scaffidi M A , Jeyalingam T , Gimpaya N , Anderson J , Grover S C , McCreath G , Walsh C M 
Published: March 2021

Abstract

Background
An increasing focus on quality and safety in colonoscopy has led to broader implementation of competency-based educational systems that enable documentation of trainees’ achievement of the knowledge, skills, and attitudes needed for independent practice. The meaningful assessment of competence in colonoscopy is critical to this process. While there are many published tools that assess competence in performing colonoscopy, there is a wide range of underlying validity evidence. Tools with strong evidence of validity are required to support feedback provision, optimize learner capabilities, and document competence.

Aims
We aimed to evaluate the strength of validity evidence that supports available colonoscopy direct observation assessment tools using the unified framework of validity.

Methods
We systematically searched five databases for studies investigating colonoscopy direct observation assessment tools from inception until April 8, 2020. We extracted data outlining validity evidence from the five sources (content, response process, internal structure, relations to other variables, and consequences) and graded the degree of evidence, with a maximum score of 15. We assessed educational utility using an Accreditation Council for Graduate Medical Education framework and methodological quality using the Medical Education Research Quality Instrument (MERSQI).

Results
From 10,841 records, we identified 27 studies representing 13 assessment tools (10 adult, 2 pediatric, 1 both). All tools assessed technical skills, while 10 assessed cognitive and integrative skills. Validity evidence scores ranged from 1–15. The Assessment of Competency in Endoscopy (ACE) tool, the Direct Observation of Procedural Skills (DOPS) tool, and the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT) had the strongest validity evidence, with scores of 13, 15, and 14, respectively. Most tools were easy to use and interpret and required minimal resources. MERSQI scores ranged from 9.5–11.5 (maximum score 14.5).

Conclusions
The ACE, DOPS, and GiECAT have strong validity evidence compared to other assessments. Future studies should identify barriers to widespread implementation and report on use of these tools in credentialing purposes.

Funding Agencies
None
A98 DEFINING TRANSITION SUCCESS ACCORDING TO YOUNG ADULTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Bihari A , Hamidi N , Seow C , Goodman K , Wine E , Kroeker K 
Published: March 2021

Abstract

Background
The incidence of childhood-onset inflammatory bowel disease (IBD) diagnoses is increasing in Canada; therefore, more patients will need to transition from pediatric into adult care. The literature on transition in IBD patients has focused mainly on preparation and while transition success is often referenced, it is not clearly defined. Prior research on IBD transition success has only focused on the perspectives of the health care providers. Taking into consideration that transition is a process that greatly relies on patient involvement, patient perspectives should be represented in defining its success.

Aims
The primary aim is to understand patients’ perspectives on the outcomes that characterize a successful transition from pediatric to adult care.

Methods
This study paired a theoretical position of naturalistic inquiry with the method of qualitative description. Purposive sampling was used to recruit patients from IBD clinics at the University of Alberta and the University of Calgary. Inclusion criteria included transition within the last two years, diagnoses with IBD for at least a year prior to transitioning, and absence of comorbidities. Virtual semi-structured interviews were conducted using an established interview guide. Interviews were transcribed verbatim and then analyzed concurrently with data collection by latent content analysis using NVivo computer software. Participant recruitment and data analysis continued until no further themes emerged from the data, which signaled that thematic saturation was achieved.

Results
Thematic saturation was achieved after 17 interviews. Among participants, 58.8% were female; 47% had a diagnosis of Crohn’s, 47% of ulcerative colitis, and one individual was diagnosed with both. The median age at diagnosis was 15 years (IQR, 3.5). The majority (94%) of participants viewed their transition as being successful. Overall, the major themes that emerged from the data were: 1. relationship with one’s adult care team, characterized predominantly as the patient being comfortable with their new team; 2. health outcomes, characterized by disease remaining stable, and medication adherence; 3. independence in one’s care, characterized by making and attending appointments on their own, asking questions and in general having an awareness about your health and disease; 4. care stability, characterized by no drop off in care, and regular contact and follow up by their provider.

Conclusions
Young adults with IBD define pediatric transition success in four themes: relationship with care team, health outcomes, independence in one’s care, and care stability. Through understanding what transition success looks like from the patients’ perspectives, health care providers can help patients achieve success as they define it.

Funding Agencies
None