bluuebunny/crossref_metadata_2025_split huggingface dataset:
A115 MODELING CYSTIC FIBROSIS (CF) INTESTINAL DISEASE USING PATIENT DERIVED TISSUES
Authors: Xia S , Laselva O , Bear C E , Jones N 
Published: February 2020

Abstract

Background
Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes for a chloride/bicarbonate anion channel expressed on the apical membrane of most epithelial tissues, such as the lungs, liver, pancreas, small and large intestines, and reproductive tissues. CFTR is responsible for the transport of chloride and bicarbonate ions to maintain tissue surface hydration and pH balance of epithelial tissues. Historically, recurrent lung infections have been the most common cause of mortality in CF patients. With advances in clinical care and therapeutics, the current mean survival age of Canadian patients has increased to 52.3 years. However, this increase in survival has also been associated with an elevated risk of developing gastrointestinal cancers in CF adults. Compared to the general public, CF patients are 10 times more likely to develop cancer. This risk is increased to 25-20 times in patients that have undergone organ transplantations. Although the exact molecular mechanism regarding increased cancer risk in CF remains unclear, chronic intestinal inflammation has been known to contribute to elevated cancer development.

Aims
CF patients display an increased baseline inflammatory status that is exacerbated with microbiome exposure leading to possible increased risk for inflammation-mediated cancer development.

Methods
To reduce inter-patient heterogeneity, we have differentiated human intestinal organoids using induced pluripotent stem cells from homozygous F508del CF patients and gene edited isogenic non-CF (Wt-CFTR) controls. We conducted gene expression studies using RT-qPCR to determine baseline differences in gene expression prior to environmental exposures and following exposure to LPS and flagellin.

Results
We determined the expression levels of stem cell, intestinal epithelial cell, innate immunity genes and differentiation markers and found expression of such genes were not significantly different between 3D CF and gene-edited non-CF organoids. We are currently conducting RNA sequencing to survey expression pattern of all genes to definitively determine possible fundamental changes in the CF intestinal epithelium and determining the effect of LPS and flagellin treatment to determine if there is an altered response to inflammatory stimuli.

Conclusions
iPSC derived HIOs is a novel, patient based, and renewable model that can be used to dissect the primary intestinal pathologies in CF. Transcriptomic data of CF HIOs at steady state will provide insights to possible developmental defects. Complex interactions between the host intestinal epithelia and the commensal microbiome can also be investigated using this model.

Funding Agencies
CAG
A128 JACKHAMMER ESOPHAGUS – A META-ANALYSIS OF PATIENT DEMOGRAPHICS, DISEASE PRESENTATION, MANOMETRY DATA AND TREATMENT OUTCOMES
Authors: Wahba G , Bouin M 
Published: February 2020

Abstract

Background
Jackhammer esophagus (JE) is a newly described esophageal motility disorder characterized by the presence of distal esophageal hypercontractility. However, there is limited data on JE and this entity remains misunderstood.

Aims
To systematically review the published clinical data on JE and present pooled data on patient demographics, disease presentation, manometry parameters and treatment outcomes from the available literature.

Methods
We performed a systematic review of clinical series on JE (based on the latest Chicago Classification criteria (v3.0)) through MEDLINE, EMBASE and Web of Science. Patient data from included studies were then extracted and random-effects meta-analyses were performed to calculate and compare pooled data.

Results
Thirty-seven studies met inclusion criteria reporting on at least one pooled variable. The pooled prevalence of JE was 1.97% [95% CI: 1.39%-2.78%] amongst patients referred for high resolution manometry (HRM) based on eleven studies reporting this data (Figure 1). The mean age at diagnosis was 60.8 years [95% CI: 57.1–64.4] and 65% [95% CI: 58%-72%] of patients were female. JE was significantly more prevalent in post-lung transplant patients and morbidly obese patients undergoing HRM (23.99% [95% CI: 9.00%-38.97%] and 5.18% [95% CI: 1.76%-14.3%] respectively). Dysphagia was the most common presentation of JE (64% [95% CI: 52%-77%]) followed by gastroesophageal reflux disease (GERD) (46% [95% CI: 26%-67%]), regurgitation (39% [95% CI: 10%-67%] and heartburn (34% [95% CI: 22%-45%]). The pooled mean distal contractile integer (DCI) of all ten standard HRM swallows was 9,535 mmHg●s●cm [95% CI: 6,978–12,093] and the pooled mean integrated relaxation pressure (IRP) was 13.9 mmHg [95% CI: 8.2–19.7]. Endoscopic treatment as a whole was more successful than medical treatment in achieving clinical symptom improvement (79% [95% CI: 74%-85%] vs. 63% [95% CI: 47%-79%]; p=0.012). The pooled clinical success rate of peroral endoscopic myotomy (POEM) specifically was 82% [95% CI: 75%-90%].

Conclusions
JE is a new motility disorder most commonly presenting with dysphagia. High clinical suspicion is important because the diagnosis can only be made through HRM and treatment outcomes are generally satisfactory.

Funding Agencies
None
A140 UNDERSTANDING PATIENTS’ PERCEPTIONS OF FECAL MICROBIOTA TRANSPLANT
Authors: Chauhan U , Popov J , Kalantar M , Wolfe M , Marshall J , Halder S L , Moayyedi P , Kaasalainen S 
Published: February 2020

Abstract

Background
Fecal microbiota transplantation (FMT) is under active investigation as a popular treatment option for a variety of diseases, including ulcerative colitis (UC). Despite increasing evidence for its therapeutic role, the current literature is limited in its scope to assess firsthand patient experiences.

Aims
To exlore perceptions, attitudes, and experiences of patients who chose to pursue FMT and patients who declined FMT in favor of conventional medications.

Methods
Using qualitative descriptive design, eligible patients were invited to participate in face-to-face semi-structured interviews before and after FMT treatment. Interviews were audiotaped, transcribed, and analyzed using thematic analysis.

Results
Main baseline themes across the FMT (n=9) and non-FMT (n=8) groups included: (i) knowledge of FMT, (ii) attitudes around FMT, and (iii) factors contributing to the decision to pursue FMT. Post-FMT themes included: (i) experiences with FMT, and (ii) perceived response to treatment. We found a poor general understanding of FMT across both cohorts, suggesting a need for improving patient education. Non-FMT patients were less likely to have heard or researched FMT in the past due to feelings of “it just sounds weird”. Similar concerns were found across both groups, including fear of transmissible infections, cost of an experimental therapy, and aversion to stool. Expectations varied between the two groups, with feelings of hope and a sense of “last resort” driving patients to pursue FMT. In contrast, the non-FMT cohort felt a need to further research FMT, explore other treatment options before committing to FMT, and were more likely to describe their disease activity as “not at the severe end”. This demonstrates that FMT may be perceived as a “last ditch effort”. Despite initial aversion, the non-FMT group demonstrated interest in learning more about FMT and felt more open to the possibility of pursuing FMT in the future. The FMT group was more likely to harbor a positive view of natural medicine and classify FMT as natural, while the non-FMT cohort expressed “I’m not really into the weird stuff”. Post-FMT, some patients expressed delight in the perceived changes in their symptoms, including improved quality of life, decreased urgency, and less concerns with accidents.

Conclusions
Our results suggest that important motivating factors for pursuing FMT are a perception of naturality and a sense of last resort. With improved education, FMT may pose an acceptable and tolerable treatment option for patients with UC.

Funding Agencies
Canadian IBD (CANIBD) Nursing
A147 ENDOSCOPIST FEEDBACK IS ASSOCIATED WITH IMPROVEMENTS IN COLONOSCOPY QUALITY INDICATORS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Bishay K , Calo N , Scaffidi M A , Walsh C M , Anderson J , Rostom A , Dube C , Keswani R N , Heitman S , Hilsden R J , Shorr R , Grover S C , González Moreno E , Forbes N 
Published: February 2020

Abstract

Background
Colonoscopy quality indicators such as adenoma detection rate (ADR) are surrogates for the effectiveness of screening-related colonoscopy. Endosocpist feedback may be associated with improvements in ADR and other quality indicators.

Aims
To conduct a systematic review and meta-analysis to determine whether an association exists between endoscopist feedback and improvements in colonoscopy quality indicators.

Methods
An electronic and manual search was conducted through May 2019 for studies reporting on endoscopist feedback and associations with ADR or other colonoscopy quality indicators. Studies primarily assessing the effect of audit and feedback on trainees and studies that included interventions other then feedback were excluded from the analysis. Pooled rate ratios (RR) and weighted mean differences (WMD) were calculated using DerSimonian and Laird random effects models. Subgroup, sensitivity and meta-regression analyses were performed to assess for potential methodological or clinical factors associated with outcomes.

Results
Of 1,326 initial studies, 12 studies were included in the meta-analysis for ADR, representing 33,184 colonoscopies. Endoscopist feedback was associated with an improvement in ADR (RR 1.21, 95% confidence interval, CI, 1.09 to 1.34). Low performers derived a greater benefit from feedback (RR 1.62, 95% CI 1.18 to 2.23) compared to moderate performers (RR 1.19, 95% CI 1.11 to 1.29), while high performers did not derive a significant benefit (RR 1.06, 95% CI 0.99 to 1.13). Feedback was not associated with increases in withdrawal time (WMD +0.43 minutes, 95% CI -0.50 to +1.36 minutes) or improvements in cecal intubation rate (RR 1.00, 95% CI 0.99 to 1.01).

Conclusions
Endoscopist feedback is associated with modest improvements in ADR. Routine audit and feedback may be a feasible strategy to optimize outcomes in screening colonoscopy.

Funding Agencies
None
A149 COMPARING THE REAL-WORLD EFFECTIVENESS OF 4L VERSUS 2L SPLIT COLONOSCOPY PREPARATIONS: PRELIMINARY DATA OF A SINGLE CENTRE EXPERIENCE THROUGH THE BRITISH COLUMBIA COLONOSCOPY SCREENING PROGRAM
Authors: Lee J G , Telford J J , Galorport C , Yonge J , Macdonnell C A , Gillies A , Chow R , Enns R A 
Published: February 2020

Abstract

Background
The British Columbia Colon Screening Program (CSP) is a population-based program offering biennial fecal immunochemical test (FIT) to individuals age 50–74 years with follow-up colonoscopy for a positive FIT as well as individuals with a personal history of neoplastic polyps or a high risk family history of colorectal cancer. Over 20,000 colonoscopies are performed annually. In December 2018, program colonoscopists in Vancouver, Canada agreed to switch from a 2L polyethylene glycol (PEG) preparation to a 4L PEG preparation after studies suggested superiority of the higher volume preparation in achieving adequate bowel cleansing and improving adenoma detection rates (ADR). High quality bowel cleansing is critical to minimize repeat procedures and maximize neoplasia detection.

Aims
To compare the quality of bowel preparation and neoplasia detection rates using the 4L high volume split preparation (HVSP) versus the 2L low volume split preparation (LVSP) in patients undergoing colonoscopy in the BC CSP.

Methods
A retrospective review of consecutive patients undergoing colonoscopy through the CSP at St. Paul’s Hospital from Dec 2017-Apr 2018 and Dec 2018-Apr 2019 was conducted. Inclusion criteria included: age 50–74, patients undergoing colonoscopy for any reason through the BC CSP. Variables collected included: patient demographics, bowel preparation qualty and pathologic findings. ADR and sessile serrated polyp detection rate (SSDR) were analyzed.

Results
462 colonoscopies were included, 280 in the LVSP group and 182 in the HVSP group. 8/280 (2.9%) had poor bowel preparation in the LVSP group, while 10/182 (5.5%) had poor bowel preparation in the HVSP group. The ADR and SSDR were 53.6% in LVSP vs. 50.0% in HVSP and 8.2% in LVSP vs. 8.8% in HVSP, respectively.

Conclusions
In this preliminary evaluation, the high volume PEG-based split preparation did not reduce the proportion of inadequate bowel preparations. Further evaluation of a larger number of colonoscopies is planned.

Funding Agencies
None
A150 ACCESS TIMES TO GASTROENTEROLOGY FOR HIGH-RISK IBD REFERRALS IN THE GREATER CALGARY REGION
Authors: St-Pierre J , Oshiomogho I , Bindra G , Kaplan G G , Panaccione R , Seow C , Nasser Y , Beck P , Jijon H 
Published: February 2020

Abstract

Background
Delay in the diagnosis of inflammatory bowel disease (IBD) can lead to adverse outcomes. In 2006, the CAG Wait Time Consensus Group recommended that wait times for patients with symptoms highly suggestive of IBD should be seen within two weeks. In 2007, the greater Calgary region established a central access and triage system to improve access to care as well as the “High-Risk IBD clinic” (HR-IBD) to further expedite the access of patients with IBD alarm symptoms. These included diarrhea, rectal bleeding, weight loss, abnormalities in laboratory and stool investigations.

Aims
The current study aimed to evaluate whether patient access to the HR-IBD clinic in the Calgary region was within recommended wait times.

Methods
We conducted a cross-sectional study of charts from consented patients pulled from the EMR of five Gastroenterologists in the Calgary region that received HR-IBD referrals from Feb 2014 to Jan 2018. Of the 206 patients included, the majority were female (139 vs 65) and the mean age was 34.4 y, with no statistical difference in age between genders (p=0.81). Data analysis was done with Stata (StataCorp 2019).

Results
The mean time to initial consult was 74.8 days (median 64), whereas time to endoscopy was 85.5 days (median 77). There was no statistical difference in the mean wait times between genders. Of the patient charts reviewed, 27% of referrals had a confirmed diagnosis of IBD (CD 17%, UC 11%). Patients with a diagnosis of UC waited a mean of 60.1 days (median 60) until initial consultation and patients with a diagnosis of CD waited 77 days (median 63.5), although this was not statistically different (p=0.27). The mean time to endoscopy for patients with UC was 77 days (median 67), and 85.4 days for patients with CD (median 78.5), again not statistically different. These wait times are below the reported wait times for all GI complaints, of 92 days from referral to consultation and 155 days from referral to procedure, as reported in the SAGE survey (2012). Although there were no differences in time to consult and endoscopy between groups, there were notable differences in alarm symptoms reported in the referral. For example, rectal bleeding was reported in 81.8% of referrals that culminated in a diagnosis of UC, as compared to 50% in CD and 47.6% of non-IBD patients. Further analysis in which alarm symptoms correlate with a final diagnosis of IBD may guide triaging of referrals to decrease the time to diagnosis.

Conclusions
Timely access for consultation and endoscopy for patients presenting with high-risk features for IBD by Gastroenterology in the Calgary region remains above the CAG recommended wait times. Further correlation of high-risk features with a final diagnosis of IBD will help risk-stratify referrals in order to decrease time to IBD diagnosis.

Funding Agencies
CIHRAlberta Innovates Health Solutions
A157 THE EFFECTIVENESS OF A STANDARDIZED BIOLOGIC CARE PATHWAY IN THE MANAGEMENT AND TREATMENT OF INFLAMMATORY BOWEL DISEASE
Authors: Willett N , Heisler C , Nazer N , Currie B , Phalen-Kelly K , Stewart M , Jones J 
Published: February 2020

Abstract

Background
Inflammatory Bowel Disease (IBD) is a class of chronic immune-mediated diseases. Biologics have revolutionized the treatment of IBD. Existing literature suggests significant variation exists in the use of biologic treatment among physicians, from provider-specific prescribing to completion of the pre-biologic workup. These differences may influence the effectiveness of achieving and maintaining long-term remission. Clinical care pathways may serve to standardize the use of biologics in the treatment of IBD leading to improvements in patient outcomes and consistency of care provided from different specialists.

Aims
To determine if the use of biologics to treat IBD managed within a standardized biologic care pathway (BCP) is safer and more effective compared to the current standard of care.

Methods
This was a retrospective, real-world cohort study of a prospectively implemented evidence-based BCP at the Nova Scotia Collaborative IBD (NSCIBD) program between 2015 and 2019. Patient inclusion criteria consisted of any adult with a diagnosis of IBD (including Crohn’s Disease, ulcerative colitis, IBD-Unclassified) aged 18 years or older who was managed within the NSCIBD program. Preliminary descriptive analyses of the data are presented. Data collection is ongoing and multivariate analyses will be presented in full at CDDW.

Results
In total 249 patients were included in the cohort study (111 BCP patients, 138 non-BCP patients). The mean age was 49 years (range of 17–86 years). Sixty-nine percent (171/249) of patients were diagnosed with CD, 28% (70/249) with UC, and 3% (8/249) with IBD-U. The mean duration of disease was 13 years (range of 0–36 years). Use of combination therapy was similar between the cohorts with 64% of BCP patients (n=102) and 63% of non-BCP patients (n=123) on combination therapy. Thirty-eight percent of the BCP cohort required dosing interval changes vs. 29% in the non-BCP cohort (0.24 fold higher in BCP cohort). Seventy-one percent of the BCP patients were exposed to TDM vs. 41% of the non-BCP cohort (0.40-fold more TDM in pathway cohort). Although 34% of BCP patients and 38% of non-BCP cohort patients reached clinical remission (n=103 and 125, respectively), 38% of BCP patients and 21% of non-BCP patients achieved endoscopic remission (0.5-fold lower in the non-BCP cohort), (n=29 and 53, respectively).

Conclusions
Preliminary analyses suggest patients managed within a BCP have their biologic management guided more often by the results of TDM and objective biomarkers than those not managed within a BCP. Although clinical remission was observed to be similar between the cohorts, attainment of endoscopic remission was more likely amongst patients managed within the BCP. Additional multivariate analyses will be presented at CDDW with a larger cohort size.

Funding Agencies
None
A166 ANALYSIS OF SYMPTOMS, DIAGNOSTIC PATTERNS, AND CANADIAN PROVIDER PERSPECTIVE OF ACUTE HEPATIC PORPHYRIA
Authors: Roblin S , Meninger S , Murray S , Karki C , Krautwurst K , Mustafina R , Ko J 
Published: February 2020

Abstract

Background
Acute hepatic porphyria (AHP) is a family of rare genetic diseases, the most common being acute intermittent porphyria (AIP). AHP results from enzyme deficiencies involved in haem synthesis, leading to accumulation of neurotoxic haem intermediates, aminolaevulinic acid (ALA) and porphobilinogen (PBG), causing potentially life-threatening attacks and chronic symptoms. Patients afflicted by AHP often remain without a proper diagnosis for up to 15 years due to lack of awareness and testing. First-line diagnostic biochemical tests include measuring spot urinary ALA and PBG as both are elevated in the majority of AHP patients.

Aims
The study aimed to describe physicians experience diagnosing AHP and characterize patients globally, including Canada.

Methods
Physicians (n=175) who actively managed AHP patients (with and without recurrent attacks) in the preceding year were recruited from 9/2017–10/2017 to complete an online survey collecting information on demographics, familiarity with AHP and diagnostic tests, perspective on symptoms important to diagnosis, referral patterns, and treatment preferences. Physicians also completed a chart review of 546 patients and reported anonymized data on demographics, medical history, attacks, and symptoms. Data was analysed using descriptive statistics.

Results
Canadian physicians (n=15) practiced a mean of 19.7 years, 67% worked in community settings, and 53% were gastroenterologists. Symptoms informing AHP diagnosis included fatigue (93%), sensory loss (87%), mental confusion (87%), Abdominal pain (80%), red/dark urine (80%), vomiting (73%). AHP diagnostic tests considered informative for diagnosis included urinary ALA (87%) and PBG (80%); however, several non-specific tests were also commonly considered informative of AHP. Chronic symptoms reported included fatigue (75%), nausea/vomiting (70%), weakness (66%), pain (58%), anxiety (54%), diarrhea (41%), constipation (40%). Canadian physicians reported a mean of 58% AHP patients they manage being initially misdiagnosed. Global patients (n=546) were aged 40 years (mean), female (52%), with AIP (83%). Canadian patients (n=38) were aged 41 years (mean), female (61%), with AIP (78%). Patients had mean of 3.4 attacks and 1.6 hospitalizations in the past year.

Conclusions
This study highlights the challenges diagnosing AHP due to non-specificity of symptoms and limited understanding of diagnostic procedures. Due to the frequent presentation of gastrointestinal symptoms, AHP should be included in gastroenterologists’ differential diagnosis of patients presenting with non-specific abdominal pain. Among patients diagnosed with AHP, both acute attacks and chronic symptoms were reported, implicating both in the disease.

Funding Agencies
Alnylam Pharmaceuticals