bluuebunny/crossref_metadata_2025_split huggingface dataset:
A160 PREVALENCE OF OUTCOME SWITCHING AMONG PUBLISHED PHASE 3 INTERVENTIONAL TRIALS FOR INFLAMMATORY BOWEL DISEASE THERAPEUTICS
Authors: Bansal R , Khan R , Gimpaya N , Scaffidi M A , Elsolh K , Verma Y , Li J , Grover S C 
Published: March 2021

Abstract

Background
Outcome switching is a well-described form of inconsistent reporting in randomized clinical trials (RCTs), wherein pre-specified primary and/or secondary outcomes are changed between trial registration and the publication of results without explanation. This is of particular concern, as the selective publication of results that are favorable will insert bias into the trial’s results and may cast doubt on the veracity of its findings. While it has been investigated in other disciplines, the prevalence of outcome switching has yet to be described among RCTs for inflammatory bowel disease (IBD).

Aims
To determine the prevalence of correctly reported pre-specified primary and secondary outcomes in published phase 3 interventional RCTs for IBD.

Methods
We identified all phase 3 interventional trials for IBD with published results using clinicaltrials.gov. We included all results with an associated publication that detailed the results of the trial. We excluded registrations if: only an abstract of the results was available; trial results were only published as a pooled analysis; multiple trial segments were reported collectively; or a publication of the results could not be identified through clinicaltrials.gov or a custom search.
Two reviewers extracted all pre-specified primary and secondary outcomes for each trial using the clinical trial registration page that was dated before the commencement of the trial. These outcomes were compared to the outcomes reported in the corresponding journal articles. Any discrepancies were noted, and additional outcomes were extracted.

Results
We identified a total of 88 phase 3 interventional RCTs for IBD, of which 57 were matched to independent publications of their results. All trials pre-specified a primary outcome, and 50 (87.7%) pre-specified secondary outcomes. 10 (17.5%) of trials did not report some or all primary outcomes, and 19 (33.3%) trials had a change or alteration to the primary outcome. Of the trials that pre-specified secondary outcomes, 16 (28.1%) did not report all pre-specified secondary outcomes. 49 (86.0%) trials added 6 (IQR: 2–8) unspecified secondary outcomes on average.

Conclusions
Many phase 3 interventional RCTs in IBD either did not report some or all primary outcomes, or altered the primary outcome. Trials routinely reported additional outcomes that were not pre-specified and failed to note that they were added post hoc. Based on these results, we recommend improvements in the reporting of pre-specified outcomes and higher fidelity in order to maintain confidence in trial results.

Funding Agencies
None
A161 PREVALENCE OF FINANCIAL CONFLICTS OF INTEREST (FCOI) AMONG PROPENSITY-SCORE MATCHED RETROSPECTIVE STUDIES EVALUATING BIOLOGIC THERAPEUTICS FOR IBD
Authors: Elsolh K , Tham D , Scaffidi M A , Bansal R , Li J , Verma Y , Gimpaya N , Khan R , Grover S C 
Published: March 2021

Abstract

Background
Inflammatory Bowel Disease (IBD) studies have commonly relied on real-world evidence to evaluate different therapies. An emerging idea has been the use of propensity score matching as a statistical method to account for baseline characteristics in IBD patients. In retrospective studies, propensity score matching of patients helps reduce treatment assignment bias and mimic the effects of randomization. Recently, propensity-score matching has become an important tool in IBD studies comparing biologic therapeutics. Biologic medications are among the highest-grossing drugs worldwide, and their pharmaceutical producers make considerable payments to physicians to market them. In spite of this, there is a lack of evidence examining the role of undue industry influence among propensity-score matched comparative studies evaluating biologic therapeutics for IBD.

Aims
Given the documented association between IBD biologics and FCOI, we hypothesize a high burden of FCOI in propensity-score matched studies. The aim of this study was to evaluate the prevalence of disclosed & undisclosed financial conflicts of Interest (FCOI) in propensity-score matched comparison studies evaluating biologics for IBD.

Methods
We developed & ran a librarian-reviewed systematic search on EMBASE, MEDLINE, and Cochrane Library databases for all propensity-score matched retrospective studies comparing biologics for the treatment of IBD. Full-text retrieval & screening was performed on all studies in duplicate. 16 articles were identified. Industry payments to authors were only considered FCOI if they were made by a company producing a biologic that was included in the comparison study. Disclosed FCOI were identified by authors’ interests disclosures in full-texts. Any undisclosed FCOI among US authors were identified using the Centre for Medicare and Medicaid Services (CMS) Open Payments Database, which collects industry payments to physicians.

Results
Based on a preliminary analysis of 16 studies, there was at least one author with a relevant FCOI in 14 (88%) of the 16 studies. 14 studies (88%) had at least one disclosed FCOI, while 6 studies (37.5%) had at least one undisclosed FCOI. Among studies with disclosed FCOI, a mean of 40.2% (SD = 23.4%) of authors/study reported FCOI. Among studies with undisclosed FCOI, a mean of 18.8% (SD = 7.0%) of authors/study reported FCOI. The total dollar value of FCOIs was $1,974,328.3. The median conflict dollar value was $5,576.6 (IQR: $321.6 to $36,394.9).

Conclusions
We found a high burden of undisclosed FCOI (37.5%) among authors of propensity-score matched studies evaluating IBD biologics. Given the potential for undue industry influence stemming from such payments, authors should ensure better transparency with industry relationships.

Funding Agencies
None
A163 MAJORITY OF INFLAMMATORY BOWEL DISEASE PATIENTS WITH RECURRENT CLOSTRIDIOIDES INFECTION DO NOT REQUIRE FECAL MICROBIOTA TRANSPLANTATION
Authors: Balram B , winczura n , Kao D H , Dieleman L A , Halloran B , Kroeker K , Peerani F , Huang V , Wong K 
Published: March 2021

Abstract

Background
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Clostridioides difficile infection (CDI) and have worse outcomes including higher rates of colectomy and death, and experience higher rates of recurrent CDI (rCDI). However, it is still not clear whether rCDI is a cause of refractory IBD or a consequence of the inflammatory state in the colon.

Aims
We aimed to assess the outcomes of rCDI in patients with active IBD compared to inactive IBD in the era of fecal microbiota transplantation (FMT)

Methods
This is a retrospective cohort of adult IBD patients with rCDI at the IBD centre at the University of Alberta hospital between 2014–2017. rCDI was defined as a recurrent episode occurring within 60 days of the prior after successful treatment with antibiotics. We collected demographic and clinical characteristics, along with the rCDI-related and FMT outcomes in patients with active and inactive IBD. Active IBD was based on clinical assessment using a combination of disease severity scores (Harvey Bradshaw Index, partial Mayo scores), presence of active disease on colonoscopy, clinical symptoms and/or treatment escalation or change in the month leading up to rCDI diagnosis.

Results
Over the study period, 56 IBD patients (50% ulcerative colitis, 28/56) had a total of 85 rCDI episodes. Thirty-four percent (19/56) of patients had two or more rCDI episodes. Forty-one percent (35/85) of rCDI episodes were toxin positive while the remainder were only PCR positive. Thirty-nine percent (33/85) had active IBD at the time of CDI diagnosis. Patients with active IBD were more likely to have rCDI (1.7 rCDI episodes vs. 1.5, p=0.018). IBD treatment escalation was also more likely in the active IBD cases (79% vs. 44%, p = 0.002) with the use of steroids (27% vs 2%, p = 0.001) and addition of biologics (18% vs. 2%, p = 0.013). Active IBD cases were also more likely to be hospitalized (30% vs. 10%, p = 0.02) and were more likely to receive FMT (27% vs. 4%, p = 0.003). There was no difference in the time between rCDI episodes, antibiotic exposure or colectomy rates between the two groups.

Conclusions
Compared to IBD patients in remission, patients with active IBD are more likely to experience rCDI, IBD treatment escalation and FMT. It is interesting to note that only 27% of patients with recurrent CDI required FMT suggesting CDI may be a marker of active or refractory disease rather than a cause. Larger, prospective studies are needed to help clarify this association.

Funding Agencies
None
A165 DOES APPENDECTOMY PREVENT THE SUBSEQUENT DEVELOPMENT OF ULCERATIVE COLITIS?: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Abdali D , Narula N 
Published: March 2021

Abstract

Background
Ulcerative colitis (UC) is a disease with a heavy burden of morbidity, for which we do not fully understand its etiology. Researchers have anecdotally observed a preventative effect of appendectomy on the risk of developing UC, with multiple studies exploring this relationship.

Aims
We aimed to complete a systematic review and meta-analysis, the largest of its kind, to determine with more certainty the effect of appendectomy on the subsequent development of UC.

Methods
A literature search and a review of reference lists of previously published articles was done to identify studies exploring the association between appendectomy and the subsequent development of UC. Our primary endpoint was the diagnosis of UC. Other variables of interest were geographical region, publication date, and age at time of appendectomy. Odds ratios with 95% confidence intervals (CI) are reported.

Results
Fifty-one studies (49 case-controls studies and 2 cohort studies) were included with a total of 1,270,332 participants. The pooled OR showed that appendectomy decreases the odds of developing UC (Figure 1; OR 0.37, 95% CI, 0.29–0.46, I2 = 89%). A similar pattern was seen for individuals who received an appendectomy before the age of 20 (Figure 2; OR 0.35, 95% CI, 0.21–0.61, I2 0%). The protective effect was seen again when including only high quality methodological studies with Newcastle-Ottawa scale ≥ 7 (Figure 3; OR 0.47, 95% CI, 0.34–0.65, I2 56%).

Conclusions
Appendectomy may be protective against subsequent development of UC. Future research should focus on the physiological explanation behind this association, and the practicality of using appendectomy as a primary prevention measure in patients at high-risk of developing ulcerative colitis.

Funding Agencies
None
A175 BEHAVIORAL INTERVENTIONS TO ADDRESS INFLAMMATORY BOWEL DISEASE-RELATED DISTRESS AND QUALITY OF LIFE: A SYSTEMATIC REVIEW AND META-ANALYSIS.
Authors: Reise-Filteau M , Heisler C , Shepherd T , Stewart M J , Jones J 
Published: March 2021

Abstract

Background
Inflammatory bowel disease-associated psychological distress (IBD-PD) (inclusive of anxiety, depression, and high levels of stress) is prevalent amongst persons living with IBD. IBD-PD impairs quality of life (QoL) and worsens disease outcomes. Research relating to the efficacy of behavioral interventions for IBD-PD has been limited.

Aims
This systematic review and meta-analysis was conducted to evaluate the efficacy of cognitive behavioral therapy (CBT)-based interventions for the management of IBD-PD and QoL in persons living with IBD.

Methods
Pre-defined criteria were used to identify randomized controlled studies reporting on the efficacy of CBT-based interventions for IBD-PD and QoL in adults living with IBD. Electronic databases including CINAHL, Cochrane Library, Embase, MEDLINE, PsycArticles, PsycInfo, Pubmed, and Web of Science were searched from inception to May 30, 2020. Studies published in English or French were included. Risk of bias was assessed using the Cochrane risk-of-bias tool by two independent reviewers (CH and MRF). Data was extracted and summarized qualitatively. A random-effects model was used to generate pooled estimates.

Results
Eight studies (922 participants) met criteria for inclusion in this review. The studies evaluated outcomes of quality of life and IBD-PD using the IBD Questionnaire (IBDQ), United Kingdom IBDQ, Short IBSQ, 36-Item Short Form Survey (SF-36), Short Health Scale, Perceived Stress Questionnaire (PSQ), Perceived Stress Scale (PSS-10), Hospital anxiety depression scale (HADS) and the Depression, Anxiety and Stress Scale-21 Items (DASS-21). Of the 8 studies, 2 were low, 2 high, and 4 at intermediate risk of bias. Interventions, duration, and outcome assessments differed across studies and observed attrition rates were high. The pooled odds ratio for the short-term impact of CBT on IBDQ (n=3) was 0.30 (95% CI 0.17- 0.44) favoring CBT. Perceived stress (PSQ and PSS-10) were only reported in 3 studies as secondary outcomes. Overall, CBT had no observed benefit for perceived stress. Measurement of anxiety and depression was inconsistent across studies. The impact of CBT on anxiety and depression varied with studies revealing both neutral and positive results.

Conclusions
In patients IBD-PD, CBT-based interventions were observed to lead to short-term improvements in disease-related QoL. The impact of CBT on IBD-PD remains unclear due to limitations in study quality and heterogeneity in study design. Further studies are needed to evaluate the efficacy of CBT-based interventions for IBD-PD and to define the role of behavioral interventions delivered within the context of collaborative, biopsychosocial models of care. Expert consensus on best practice for CBT-based interventions and IBD-PD evaluation are needed.

Funding Agencies
None
A182 INFLAMMATORY BOWEL DISEASE AMONG SENIORS IN SASKATCHEWAN
Authors: Shahmoradi A , Fowler S , Peña-Sánchez J 
Published: March 2021

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic inflammatory condition comprised of two major disorders: ulcerative colitis (UC) and Crohn’s disease (CD).The age of onset for many patients with UC and CD is between 15 and 30 years, with a second peak between 50 and 80 years of age.

Aims
We aim to determine if there are differences in disease characteristics, outcomes, and IBD-related health care utilization between elderly patients with IBD diagnosed at a young age compared to those diagnosed later in life.

Methods
A retrospective chart review of elderly (age ≥ 60 years) patients with IBD was conducted.Patients aged ≥ 60 years who were seen at the Saskatchewan Multidisciplinary IBD Clinic at the Royal University Hospital from 2012 to 2020 were included. Information on demographics, disease characteristics, and access to IBD-related health care was collected. Patients were divided in two groups according to age of diagnosis: &lt;60 and ≥ 60 years. Chi-squares were used to compare the groups. Charts with missing data were omitted in the final analysis. Three patients with indeterminant colitis were excluded from the analyses. Logistic regression models were built to obtain odds ratios (OR) with their corresponding 95% confidence intervals (95%CI) and considering potential confounders.

Results
In total, 264 patients were included in the study; 210(79.5%) diagnosed &lt;60 and 54(20.5%) ≥ 60. The mean age of diagnosis was 47.21(SD=16.18), [&lt;60=41.69(SD=13.25), ≥60=68.00(SD=6.264)].Cross tabulation (Table 2) of age of diagnosis and patient’s characteristics (sex, IBD type, and clinical remission at last visit, current use of biologics and steroids) confirmed lack of inter-variable significance. However, in the same analysis individuals diagnosed ≥ 60 were more likely to be on 5-ASA therapy compared to their counterparts diagnosed before the age of 60. Logistic regression model results demonstrated that: Patients diagnosed ≥ 60 years were 2.06 (1.12–3.80, 95% CI) times more likely to be using 5-ASA therapy.Patients in clinical remission were 3.04 (95% CI, 1.65–5.61) times more likely to be using biologic therapy.

Conclusions
Thus far, the results indicate significant correlation between use of 5-ASA in patients diagnosed age ≥60. In the same cohort, clinical remission was also linked to current use of biologics agents. On further analysis, with data stratification based on type of IBD, the same significance did not hold true, likely associated with low power within the stratified group. Clinical remission with those diagnosed ≥60 years while on biologics treatment, may reflect the specific disease type and inflammatory pathways responsible for second wave of IBD diagnosis in later ages.Patients diagnosed later in life were less likely to have IBD-related hospitalization or surgery, likely a reflection of shorted disease history.

Funding Agencies
NoneNone
A198 LEFLUNOMIDE-INDUCED COLITIS IN IMMUNOSUPPRESSED PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS
Authors: Chis R , Gladman D , Vajpeyi R , Cino M 
Published: March 2021

Abstract

Background
Leflunomide is an oral disease-modifying antirheumatic drug (DMARD), with anti-inflammatory and immunomodulatory properties that has been in use since 1998. Common leflunomide side-effects include gastrointestinal symptoms (nausea, abdominal pain and diarrhea), occurring in 10–20% of patients treated with leflunomide. Scarce evidence exists that leflunomide can cause colitis.

Aims
We present the case of a 61-year-old female, with Lupus Erythematosus who presented with colitis induced by long-term leflunomide treatment.

Methods
Case report and review of literature

Results
A 61-year-old female was seen by the gastroenterology team with complaints of diarrhea ongoing for 6 weeks associated with 10 lb weight loss. The patient had a complex medical history, including lupus, hypothyroidism, asthma, atrial fibrillation, recurrent C. difficile infection, Bell’s palsy and avascular necrosis secondary to long-term corticosteroid therapy. Previous immunosuppressive therapies included prednisone, mycophenolic acid (Myfortic), hydroxychloroquine, azathioprine, mycophenolate (CellCept) but due to multiple intolerances, she was initiated on leflunomide in 2014 and has been maintained on it since.
Stool analysis ruled out infectious causes. COVID-19 testing was also negative. A CT of the abdomen revealed pancolitis. This was confirmed on colonoscopy, which revealed mild, Mayo 1 pancolitis and normal terminal ileum. She was initiated on Mezavant as a treatment for possible ulcerative colitis. However, during the hospitalization her symptoms, worsened and bloody diarrhea was noted. She underwent a subsequent endoscopic evaluation which revealed more severe disease, Mayo 2–3 colitis, with mucosal hyperemia and ulcerations, as well as effacement of the vasculature. Initial pathology results revealed mild colitis, but repeat pathology results revealed moderate active colitis, with cryptitis, crypt abscesses and significant apoptosis consistent with drug-induced colitis. Given these findings, the diagnosis of leflunomide-induced colitis was made. Leflunomide was therefore discontinued, the patient was initiated on a higher dose of corticosteroids and cholestyramine was initiated. Following these measures, her diarrhea resolved.

Conclusions
Leflunomide may cause diarrhea in up to 33% of patients. Challenges related to the diagnosis of leflunomide-induced colitis exist, including the rarity of the diagnosis, a not completely understood mechanism for acute leflunomide-induced diarrhea, as well as variable endoscopic and histologic findings associated with the diagnosis. This report illustrates a case of leflunomide-induced colitis which should be considered in patients on leflunomide, who present with symptoms of abdominal pain and diarrhea, even years after medication initiation.

Funding Agencies
None
A202 ROLE OF EXTRACELLULAR VESICLES IN GIARDIA-MICROBIOTA INTERACTIONS.
Authors: Siddiq A , Allain T , Dong G , Olivier M , Buret A 
Published: March 2021

Abstract

Background
Extracellular vesicles (EVs) have emerged as important mediators of host-parasite interactions. Studies in various parasites have shown that EVs have important roles in pathogenesis. The protozoan parasite Giardia duodenalis, which causes diarrheal disease, produces EVs in response to changes in the environment. However, their exact role in the pathogenesis of giardiasis remains unclear. In this study, we investigate the effects of Giardia EVs on the gut commensal bacteria. EVs mediated disruption of the microbiota represents a novel mechanism that has not been investigated before.

Aims
We hypothesize that Giardia EVs contain virulence factors that will modify the growth and behavior of commensal bacteria. Based on our hypothesis, the study has three aims:
1. Quantify and characterize the EVs produced by Giardia under varying conditions.
2. Examine the effects of Giardia EVs on commensal bacteria.
3. Identify proteins and virulence factors in Giardia EVs using proteomics.

Methods
G. duodenalis (isolate NF) was exposed to bile or left untreated and the EVs were isolated using Exo-Easy Maxi Kit (Qiagen). The isolated EVs were characterized using Nanosight track analysis (NTA) and transmission electron microscopy. To examine the effects of EVs on bacteria, we used a lab strain E.coli HB101 and human isolate E. cloacae. The bacteria were incubated with Giardia EVs and their growth rate was monitored using a bacterial kinetics assay. The swimming motility of bacteria exposed to Giardia EVs was assessed on a 0.3% agar. Additionally, the ability of the EVs treated bacteria to adhere to epithelial cells was also examined. Proteomic analysis of EVs was conducted using liquid chromatography with tandem mass spectrometry.

Results
Results indicate that bile treated Giardia trophozoites produce more EVs as compared to untreated trophozoites. Giardia EVs exerted bacteriostatic effects on E.coli HB101 and E. cloacae. Additionally, Giardia EVs significantly increased the swimming motility of both E.coli HB101 and E. cloacae as well as their adhesion to the intestinal epithelial cells. Finally, proteomic analysis of EVs revealed the presence of well-characterized Giardia virulence factors such as cysteine proteases, tenascins, variant surface proteins as well as metabolic enzymes such as arginine deaminase and ornithine carbamoyltransferase.

Conclusions
Our research highlights a novel mechanism of Giardia’s interaction with commensal bacteria. Our results indicate that Giardia can release EVs in response to changes in the environment. These EVs also contain virulence factors that can modify the growth and behavior of commensal bacteria. These effects may have significant implications in disease pathophysiology. The results of the study can also be applied to other parasitic diseases where the production of EVs has been shown to play a role in the pathogenesis process.

Funding Agencies
NSERC