Crohn's Disease Is Associated with Decreased CYP3A4 and P-Glycoprotein Protein Expression.

Cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) have broad substrate overlap and are involved in the metabolism and transport of nearly 50% of currently prescribed medications. In the intestine, CYP3A4 and P-gp are coexpressed in the enterocytes at the intestinal villous tip and act in a coordinated manner to limit drug and xenobiotic oral bioavailability prior to further metabolism and disposition in the liver. Crohn's disease (CD), a form of inflammatory bowel disease, introduces a transmural intestinal insult that disrupts the intestinal barrier function; it therefore has the potential to affect intestinal drug metabolism and transport. We hypothesized that individuals with CD have reduced intestinal expression of CYP3A4 and P-gp. We obtained intestinal biopsy samples from individuals with and without CD and quantified the expression of CYP3A4 and P-gp. When we carried out Western analysis for protein expression, we observed a significant reduction in ileal (45% decrease) and colonic (78% decrease) CYP3A4 protein expression in subjects with CD compared with those without. Similarly, an 85% reduction in colonic P-gp protein expression was seen in the CD patients. Our data highlight important and novel findings pertaining to CD-associated changes to the intestinal expression of CYP3A4 and P-gp that are of relevance to better predict substrate drug dosing for patients with CD.

The safety and efficacy of adalimumab in patients with Crohn's disease: the experience of a single Canadian tertiary care centre.

BACKGROUND. Adalimumab (ADA), an antitumor necrosis factor (anti-TNF) monoclonal antibody, is effective in treating moderate-to-severely active Crohn's disease (CD). ADA has been associated with a variety of adverse events (AE). The purpose of this study is to determine the safety and efficacy of ADA in CD patients in clinical practice. METHODS. A retrospective analysis was performed on CD patients treated with ADA. Data extracted and analyzed included patient and CD demographics, remission and response rates with ADA, and safety and tolerability of ADA. RESULTS. A total of 149 ADA-treated CD patients were included. The mean duration of therapy with ADA was 20 months with 32% of patients discontinuing treatment. Anti-TNF-naïve and anti-TNF-exposed patients on ADA achieved clinical remission in 45% and 32%, had a clinical response in 23% and 23%, and had no clinical response in 32% and 45%, respectively. Anti-TNF-naïve and anti-TNF-exposed patients maintained remission in 82% and 67%, respectively. Fistulas healed in 19% and improved in 19%. AE occurred in 38% of patients with infection being the most common (20%). Serious infections lead to death in one (<1%). Logistic regression of AE did not identify statistically significant predictors except for colonic disease location (odds ratio [OR] = 0.31, 95% CI = 0.12-0.82, p = 0.018) and the rate of ADA discontinuation (OR = 3.24, 95% CI = 1.58-6.64, p = 0.0013). CONCLUSION. ADA is an effective treatment for CD. AE can occur commonly leading to discontinuation of medication and may be influenced by disease location. Although serious complications are rare, close monitoring of all patients on ADA is needed.

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease.

Background: The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). Aims: To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. Methods: This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Results: Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. Conclusion: CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

The safety and tolerability of methotrexate for treating patients with Crohn's disease.

GOALS: To determine the safety and tolerance of methotrexate for treating patients with Crohn's disease in clinical practice. BACKGROUND: Methotrexate is effective for treating patients with Crohn's disease. However, concerns about potential toxicity, particularly to the liver, have limited its use. STUDY: A retrospective chart review was performed of Crohn's disease patients in our practice treated with methotrexate. Data related to the safety and tolerance of methotrexate was extracted and analyzed. RESULTS: Of 92 patients treated with methotrexate, there was enough data for 79 patients for analysis (49 women and 30 men; mean age 28.8 y). Forty-two patients (53%) had previously received azathioprine. Overall, 40 patients (51%) achieved and maintained remission on methotrexate, including 13 of 30 (43%) who concomitantly received anti-tumor necrosis factor therapy. The mean total accumulated dose of methotrexate was 1727 mg [SD 1572 mg], with a mean total duration of methotrexate use of 25.4 months (SD 43.1 mo). The most common adverse events were nausea (22%) and elevated liver enzymes (10%). Only 6% of patients stopped methotrexate therapy because of persistently abnormal liver enzymes. No patients underwent liver biopsy. CONCLUSIONS: This retrospective study showed that methotrexate is safe and well-tolerated in treating patients with Crohn's disease in clinical practice.

Subcutaneously Administered Anti-TNFs for the Treatment of Ulcerative Colitis: A Retrospective, Propensity Score-Matched, US Health Claims Analysis.

INTRODUCTION: Adalimumab and golimumab are subcutaneously administered anti-tumor necrosis factor α (TNFα) biologics used in the treatment of ulcerative colitis (UC). To date, no studies have directly compared treatment patterns and healthcare resource utilization (HRU) among patients with UC receiving these therapies in a real-world setting. The objective of this study was to compare these outcomes among patients with UC treated with either adalimumab or golimumab using a US claims database. METHODS: Patients with UC treated with golimumab or adalimumab were identified using the US Optum Clinformatics® Data Mart database. Outcomes of interest included treatment patterns (discontinuations, dose optimizations, persistence, and concomitant medication use) and HRU (outpatient office visits, emergency room [ER] visits, and inpatient stays). Propensity score matching (PSM) was used to account for differences in confounding variables between groups. RESULTS: Overall, 990 patients were identified (golimumab: n = 277; adalimumab: n = 713). After PSM, 246 patients were included in each group. There were no significant differences between the adalimumab and golimumab groups over the full follow-up period in terms of treatment discontinuations (53.7% vs. 51.2%; P = 0.5881), dose optimizations (35.4% vs. 39.4%; P = 0.3515), or persistence (338.2 vs. 361.2 days; P = 0.4194). During the year after initiating therapy, there were no significant differences in concomitant immunosuppressant (21.9% vs. 21.7%; P = 0.9686) or corticosteroid use (74.7% vs. 78.8%; P = 0.3573) or in HRU outcomes including outpatient office visits (93.3% vs. 94.0%; P = 0.7660), ER visits (15.2% vs. 10.9%; P = 0.2238), and inpatient stays (15.2% vs. 13.6%; P = 0.6680). CONCLUSIONS: In this nationwide PSM cohort study of patients with UC receiving golimumab or adalimumab, no significant differences were observed between groups for treatment patterns or HRU outcomes. High rates of concomitant corticosteroid use, treatment discontinuations, and HRU while on therapy highlight key unmet needs in the treatment of UC.

Pretreatment HLADQA1-HLADRB1 Testing for the Prevention of Azathioprine-Induced Pancreatitis in Inflammatory Bowel Disease: A Prospective Cohort Study.

INTRODUCTION: Azathioprine-induced pancreatitis is an idiosyncratic and unpredictable response, occurring in up to 7% of azathioprine-exposed patients with inflammatory bowel disease (IBD). The haplotype HLADQA1-HLADRB1*07:01A>C is strongly associated with azathioprine-induced pancreatitis in IBD. We aimed to evaluate whether pretreatment HLADQA1-HLADRB1*07:01A>C screening will reduce the risk of azathioprine-induced pancreatitis. METHODS: Participants with IBD were screened for HLADQA1-HLADRB1*07:01A>C, and participants with a variant genotype were excluded from azathioprine treatment. Wild-type participants were started on azathioprine and followed for 3 months. The incidence of pancreatitis was compared with unscreened historical controls. RESULTS: HLADQA1-HLADRB1*07:01A>C screening resulted in an 11-fold reduction in the incidence of azathioprine-induced pancreatitis (n = 1/328 or 0.30% vs n = 13/373 or 3.4%). In propensity score-matched cohorts (age and sex), HLA DQA1-HLADRB1*07:01A>C screening was significantly associated with a reduction in the incidence of AZA-induced pancreatitis independent of weight, glucocorticoid exposure, and smoking status (adjusted odds ratio = 0.075, 95% confidence interval = 0.01-0.58, P = 0.01). Up to 45% (n = 271/599) of participants were excluded from azathioprine therapy based on the haplotype in the HLADQA1-HLADRB1*07:01A>C-screened cohort. DISCUSSION: HLADQA1-HLADRB1*07:01A>C screening reduced the risk of azathioprine-induced pancreatitis; however, using this strategy to guide the use of azathioprine therapy in IBD may eliminate a large proportion of patients from being eligible for treatment with azathioprine. In regions where there is access to other IBD therapies, and given the short-term and long-term toxicities associated with azathioprine, HLADQA1-HLADRB1*07:01A>C-screening may be a clinically relevant strategy for enhancing the safe use of azathioprine in IBD. In addition, cost-effectiveness analyses are needed to further solidify the utility of HLADQA1-HLADRB1*07:01A>C screening in IBD populations.

Safety of Combination Biologic and Antirejection Therapy Post-Liver Transplantation in Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) post-liver transplant (LT) may have bowel inflammation requiring biologic therapy. We aimed to evaluate the safety of combination biologic and antirejection therapy in IBD patients after LT from a tertiary center case series and an updated literature review. METHODS: Inflammatory bowel disease patients undergoing LT between 1985 and 2018 and requiring combination biologic and antirejection therapy post-LT were identified from the London Health Sciences Transplant Registry (Ontario, Canada). Safety outcomes were extracted by medical chart review. For an updated literature review, EMBASE, Medline, and CENTRAL were searched to identify studies evaluating the safety of combination biologic and antirejection therapy in IBD patients. RESULTS: In the case series, 19 patients were identified. Most underwent LT for primary sclerosing cholangitis (PSC; 14/19, 74%) treated with anti-integrins (8/19, 42%) or tumor necrosis factor α (TNF) antagonists (6/19, 32%). Infections occurred in 11/19 (58%) patients, most commonly Clostridium difficile (4/19, 21%). Two patients required colectomy, and 1 patient required re-transplantation. In the literature review, 13 case series and 8 case reports reporting outcomes for 122 IBD patients treated with biologic and antirejection therapy post-LT were included. PSC was the indication for LT in 97/122 (80%) patients, and 91/122 (75%) patients were treated with TNF antagonists. Infections occurred in 32/122 (26%) patients, primarily Clostridium difficile (7/122, 6%). CONCLUSIONS: Inflammatory bowel disease patients receiving combination biologic and antirejection therapy post-LT appeared to be at increased risk of Clostridium difficile. Compared with the general liver transplant population in the published literature, there was no increased risk of serious infection.

Systematic review with meta-analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies.

BACKGROUND: Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. AIMS: To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo-controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random-effects model. Meta-regression was performed to assess trial-level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. RESULTS: Thirty-two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co-prescribed aminosalicylates was 80.7% (95% CI 75.5%-85.1%), with considerable observed heterogeneity (I2  = 95%). In univariable meta-regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. CONCLUSIONS: Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy.

Association between proton pump inhibitors and respiratory infections: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections. OBJECTIVE: To examine the association between PPI treatment and respiratory infections. METHODS: A literature search was conducted using PubMed, MEDLINE and Cochrane databases of randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies that listed and quantified the specific adverse events of 'respiratory infection' or 'upper respiratory infection' (or equivalent), and compared their rates between PPIs and placebo were included. The chi(2) analysis was used to calculate the significance of association in individual studies and a meta-analysis of the selected studies was performed. RESULTS: Of 7457 studies initially identified and 70 relevant randomized, controlled trials (RCTs) selected, seven studies met the inclusion criteria. A total of 16 comparisons for chi(2) analysis were possible given the multiple dosage arms used in several studies. PPIs included in the studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than one-half of the studies showed a trend toward an association between PPI use and respiratory infections, although the majority of the studies failed to show a significant correlation. A single study using high-dose esomeprazole (40 mg) showed a significant association -4.3% rate of respiratory infections in the active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed a trend toward an association between PPIs and respiratory infections, although it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17). CONCLUSION: Although a trend was evident in both a chi(2) analysis of individual studies and a meta-analysis, the present review and meta-analysis failed to show a conclusive association between PPIs and respiratory infections. Very few RCTs actively sought out respiratory infections, which excluded the majority of RCTs identified. A well-structured, placebo-controlled prospective study would be needed to determine whether a true association between PPIs and respiratory infections exists.

Inflammatory bowel disease patients prioritize mucosal healing, symptom control, and pain when choosing therapies: results of a prospective cross-sectional willingness-to-pay study.

BACKGROUND: Given the large armamentarium of therapies for inflammatory bowel disease (IBD), physicians cannot fully describe all treatments to patients and, therefore, make assumptions regarding treatment attributes communicated to patients. This study aimed to assess out-of-pocket willingness-to-pay that IBD patients allocate to treatment attributes. METHODS: Adult patients receiving therapy for IBD were invited to access a cross-sectional web-based discrete-choice experiment (May 22-August 31, 2015) that presented paired medication scenarios with varying efficacy, safety, and administration parameters. Preference weights and willingness-to-pay for each attribute level were assessed by a hierarchical Bayes method including a multinomial logit model. RESULTS: A total of 586 IBD patients were included, 404 (68.9%) with Crohn's disease and 182 (31.1%) with ulcerative colitis. Genders were evenly distributed; the majority of patients (70.1%) were 50 years or younger and had postsecondary education (75.4%), while the median health status was 7 (Likert scale: 1 [poor] - 10 [perfect]). Regarding relative preference-weight estimates, for the average respondent, reducing pain during administration, mucosal healing, and symptom relief were the highest-ranking attributes. Conversely, infusion reactions and risk of hospitalization or surgery were the lowest-ranking attributes. In multivariate analysis, patient sociodemographics did not affect the rank order of attributes although small differences were observed between asymptomatic and symptomatic patients in the previous year. CONCLUSION: This study has important implications related to understanding patient preferences and designing patient-centered strategies. IBD patients prioritize treatments with low administration pain. Additionally, these results concur with treatment guidelines emphasizing patients' preference for mucosal healing and symptom control.

Resource implications for a population-based colorectal cancer screening program in Canada: a study of the impact on colonoscopy capacity and costs in London, Ontario.

OBJECTIVE: Cancer Care Ontario has recommended a population-based colorectal cancer (CRC) screening program using fecal occult blood testing. Patients who test positive should undergo further investigation, preferably colonoscopy. So far, no studies have been performed to quantify the costs or demands on the health care system at the community level. The number of consultations, colonoscopies and polypectomies, and the corresponding direct medical costs generated by the CRC screening program, between 2006 and 2015 in London, Ontario, were estimated using a decision analysis model in comparison with the population health model. METHODS: A faxed survey study was conducted to examine the current CRC screening practice among family physicians in London. Data from the survey and randomized studies were applied to a decision analysis model, which simulated the steps involved in population-based biennial and annual CRC screening between 2006 and 2015. The number of consultations, colonoscopies and polypectomies, and their associated costs were calculated. RESULTS: For a cohort population of 140,000, between 50 and 74 years of age, in 2006 to 2015, it is estimated that an average of 412 consultations, 463 colonoscopies and 174 polypectomies will be performed per 100,000 screen eligible population per year in biennial screening, and double in annual screening, reflecting an average of 8.7% or 17.6% increase annually in outpatient colonoscopies, respectively, compared with 2003. A mean of $285,000 or $562,000 per year would be required to support the extra consultation and endoscopic procedures generated by the biennial or annual screening. CONCLUSION: Population-based fecal occult blood testing screening for CRC appears to be a manageable strategy if a modest increase in endoscopic resources is allocated.

The Utility of Endoscopic Biopsies in Patients with Normal Upper Endoscopy.

Background and Aims. Upper endoscopy is a valuable tool in the workup of gastrointestinal (GI) complaints. The purpose of this study is to determine cost and yield of taking biopsies in a normal upper GI tract. Methods. This is a retrospective study where all upper GI biopsies were identified between May 2012 and April 2013, at a tertiary care center. Clinical, procedural, and pathology reports were reviewed to identify patient demographics, procedure information, and pathology diagnosis. Results. Biopsies of the upper GI tract were taken in 1297 patients with normal upper endoscopies. In patients with normal upper endoscopy, 22% of esophageal, 44% of gastric, and 12% of duodenal biopsies were abnormal. The most frequent abnormality was reflux esophagitis in 16% of esophageal biopsies, chronic gastritis in 23% of gastric biopsies, and increased intraepithelial lymphocytes in 6% of duodenal biopsies. The additional cost for taking biopsies in a normal upper GI tract for a diagnosis of eosinophilic esophagitis was $2963 Canadian (CAD), H. pylori associated gastritis was $1404 CAD, and celiac disease was $3024 CAD. Conclusions. The yield of biopsy in normal upper endoscopy varied with location, but the additional expense can be costly and should be tailored to appropriate clinical situations.

Efficiency and patient experience with propofol vs conventional sedation: A prospective study.

AIM: To determine whether anaesthesiologist-administered sedation with propofol (AAP) or endoscopist-administered conscious sedation (EAC) with fentanyl/midazolam shortens colonoscopy duration/total room time. METHODS: This is a prospective, non-randomized, comparative study that enrolled patients greater than 18 years of age undergoing colonoscopy in a single Canadian academic outpatient endoscopy unit over a three-month consecutive period. Colonoscopies in this unit are performed both with AAP and EAC. Patient demographics, procedure-related data and adverse events were documented. Additionally, the level of procedure difficulty, and whether a staff endoscopist, trainee with assistance, or independent trainee, performed the procedure were documented. A validated modified 4-question, 5-point Likert scale telephone survey was used to assess patient satisfaction with colonoscopy. The telephone patient satisfaction survey was conducted 24-72 h following the procedure. RESULTS: Two hundred and thirty patients were enrolled during the study period with 126 patients in the AAP group and 104 patients in the EAC group. Mean procedure time was 18.3 ± 10.1 min in the AAP group and 14.7 ± 7.1 min in the EAC group (P = 0.002). Mean total room time was 36.8 ± 13.7 with AAP and 30.1 ± 11 min with EAC (P < 0.001). Multivariate analysis revealed the use of AAP (P = 0.002), resident participation (P < 0.001), diagnostic interventions (P = 0.033), therapeutic interventions (P < 0.001), lower body mass index (P = 0.008) and American Society of Anaesthesiologist class (P = 0.016), to be predictors of longer total room time. Patient age and gender were not significant predictors. After excluding cases in which trainees were involved, there was no significant difference in procedure time between the two groups (P = 0.941), however total room time was still prolonged in the AAP group (P = 0.019). The amount of pain experienced was lower with AAP (P = 0.02), with a trend toward overall higher patient satisfaction (P = 0.074). There were 2 sedation-related adverse events, both in the AAP group involving a patient with aspiration requiring hospitalization and a patient with hypoxia managed with bronchodilators. CONCLUSION: EAC results in reduced total room time compared to AAP. Resident participation doubles procedure time regardless of sedation type.

A survey of Canadian gastroenterologists about the use of methotrexate in patients with Crohn's disease.

BACKGROUND: Methotrexate (MTX) is effective in remission induction and maintenance in steroid-dependent Crohn's disease (CD), but is often considered to be a second-line immunosuppressive agent, to be used in cases of failure or intolerance to azathioprine (AZA) or 6-mercaptopurine (6-MP). This may be related to concerns about hepatotoxicity, but this adverse effect is rare in monitored CD patients taking MTX. Still, there are no guidelines for monitoring patients with CD on MTX, and physicians must decide based on rheumatological literature about how to monitor their patients. PURPOSE: To determine the patterns of MTX use in patients with CD by Canadian gastroenterologists, examining the reasons for choosing MTX versus AZA/6-MP, the doses and routes of administration of MTX, and how patients on MTX are monitored, including the use of liver biopsy. METHODS: A self-report survey was sent to physician members of the Canadian Association of Gastroenterology, with a second mailing three months later to increase response rate. RESULTS: Of 490 surveys mailed, a 54.9% response rate was achieved. Of adult gastroenterologists, 60.7% stated they never use MTX as a first-line immunosuppressive agent, and 33.3% never use MTX at all. The most common reasons for choosing MTX were a contraindication to the use of AZA/6-MP (43.7%) and patient preference (22.5%). MTX is used intramuscularly in 41.5%, subcutaneously in 31.8%, and orally in 26.7% of patients. The most common dose used for remission induction was 25 mg/week (84.2%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly) and for remission maintenance was 15 mg/week (55.4%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly). Most responders checked a liver profile and complete blood count at baseline and serially. Of those who used MTX, 26.5% routinely performed liver biopsy after an accumulated dose of MTX had been taken (usually 1 g to 2 g), 57.7% sometimes performed liver biopsy, and 16.8% never performed liver biopsy. Of pediatric gastroenterologists, 17.6% never used MTX, but those who used it prescribed it subcutaneously (80.0%) more often than intramuscularly (17.5%) or orally (2.5%). CONCLUSIONS: MTX was used as a first-line immunosuppressive agent in patients with CD by a minority of Canadian gastroenterologists. When used, there is variability in how MTX is prescribed and monitored. Although hepatotoxicity is rare, liver biopsy was performed frequently and probably often unnecessarily.

Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study.

BACKGROUND AND AIM: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. PATIENTS AND METHODS: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver-operator characteristics (ROC) curve was used to identify the ideal FC cutoff that predicts endoscopic disease activity. Correlation between FC and endoscopic disease activity, disease location, and C-reactive protein (CRP) levels were measured. RESULTS: One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 µg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 µg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 µg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity. CONCLUSIONS: FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD.

Computer-based virtual reality colonoscopy simulation improves patient-based colonoscopy performance.

BACKGROUND: Colonoscopy simulators that enable one to perform computer-based virtual colonoscopy now exist. However, data regarding the effectiveness of this virtual training are limited. OBJECTIVE: To determine whether virtual reality simulator training translates into improved patient-based colonoscopy performance. METHODS: The present study was a prospective controlled trial involving 18 residents between postgraduate years 2 and 4 with no previous colonoscopy experience. These residents were assigned to receive 16 h of virtual reality simulator training or no training. Both groups were evaluated on their first five patient-based colonoscopies. The primary outcome was the number of proctor 'assists' required per colonoscopy. Secondary outcomes included insertion time, depth of insertion, cecal intubation rate, proctor- and nurse-rated competence, and patient-rated pain. RESULTS: The simulator group required significantly fewer proctor assists than the control group (1.94 versus 3.43; P ≤ 0.001), inserted the colonoscope further unassisted (43 cm versus 24 cm; P=0.003) and there was a trend to intubate the cecum more often (26% versus 10%; P=0.06). The simulator group received higher ratings of competence from both the proctors (2.28 versus 1.88 of 5; P=0.02) and the endoscopy nurses (2.56 versus 2.05 of 5; P=0.001). There were no significant differences in proctor-, nurse- or patient-rated pain, or attention to discomfort. CONCLULSIONS: Computer-based colonoscopy simulation in the initial stages of training improved novice trainees' patient-based colonoscopy performance.

Opioid use is associated with decreased quality of life in patients with Crohn's disease.

BACKGROUND/AIMS: Quality of life is an important consideration in the management of patients with Crohn's disease. Previous studies suggest that Crohn's disease patients using opioids may have decreased quality of life and increased risk of mortality. Our aim was to determine the association between health-related quality of life (HRQoL) and opioid use in patients with Crohn's disease while controlling for disease severity. PATIENTS AND METHODS: We conducted a cross-sectional study recruiting Crohn's disease patients at our center. Disease activity was measured using the Harvey-Bradshaw Index (HBI), and HRQoL was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: We enrolled 38 Crohn's disease patients using opioids and 62 patients not using opioids. Patients using opioids had an increased duration of disease (median 18.5 vs. 9 years, P = 0.005), increased surgeries related to Crohn's disease (median 3 vs. 0, P < 0.001), and increased prednisone use (29% vs. 11.3%, P = 0.03). Patients using opioids had increased disease activity (median HBI score 9.0 vs. 3.0, P < 0.001). Quality of life was lower in patients using opioids (mean IBDQ score 109.3 vs. 162.9, P < 0.001). This finding was significant when controlling for HBI scores, number of previous surgeries, and prednisone use (P = 0.003). CONCLUSIONS: Opioid use in Crohn's disease patients appears to be associated with disease activity and severity. HRQoL is markedly decreased in patients using opioids and this association is significant even when controlling for variables reflecting disease severity. Our findings suggest that Crohn's disease patients using opioids are likely to be significantly impacted by their disease.