Initiation of vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A prospective 24-week study with imaging assessments.

BACKGROUND: A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested. AIMS: We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI). METHODS: A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn's disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24 weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24 weeks. RESULTS: Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2 years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48 years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response. CONCLUSION: Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24 weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD.

Cannabis Use in Patients With Inflammatory Bowel Disease Following Legalization of Cannabis in Canada.

Background: Cannabis is used by patients with Crohn's disease (CD) and ulcerative colitis (UC) as an alternative to, or in combination with, conventional therapies to treat symptoms such as abdominal pain, poor sleep, and reduced appetite. The clinical efficacy of cannabis for these disorders is controversial, with some studies showing harmful outcomes associated with its use. Previous studies suggest that cannabis is used by ~12% of patients with UC and ~16% of patients with CD in the USA despite legal prohibition. Methods: We conducted a prospective cohort study of adult patients with inflammatory bowel diseases (IBD) followed in a Canadian tertiary care center. Patients completed an online 40-question survey that included demographics, IBD disease history, cannabis use, and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Results: Completed surveys were obtained from 254 participants (148 with CD, 90 with UC, and 16 with indeterminate colitis). Recent cannabis use was reported by 41% of CD and 31% of UC participants. Interestingly, only 46% of participants who used cannabis discussed their use with their physician. Participants who recently used cannabis reported more abdominal pain, poor appetite, and flatulence, and importantly this was associated with lower SIBDQ scores (recent use 37 vs non-recent use 40). Conclusions: Cannabis use among patients with IBD has more than doubled since its legalization. Cannabis use is associated with worse abdominal symptoms and quality of life. Physicians should inquire about cannabis use and optimize symptom control with evidence-based therapies.

Severity of coeliac disease and clinical management study when using a non-metabolised medication: a phase I pharmacokinetic study.

OBJECTIVE: The non-metabolised antihistamine fexofenadine has oral absorption resulting from transporter activity. Uptake by enterocyte organic anion transporting polypeptides and efflux by an ATP-binding cassette transporter (P-glycoprotein) are primary determinants. Coeliac disease-mediated lesions to the small intestinal mucosa may alter oral absorption of the drug probe, fexofenadine. DESIGN: A phase I, open-label, single-dose, pharmacokinetic study SETTING: London, Ontario, Canada PARTICIPANTS: Patients with coeliac disease (n=41) with positive serology and healthy individuals (n=48). MAIN OUTCOME MEASURES: Patients with coeliac disease-duodenal histology and oral fexofenadine pharmacokinetics within a 3-week period. Healthy individuals-oral fexofenadine pharmacokinetics with water and grapefruit juice. RESULTS: Patients with coeliac disease were stratified by disease severity: Group A (n=15, normal), B+C (n=14, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=12, moderate to severe villous blunting). Patients with coeliac disease in groups A, B+C and D and healthy individuals receiving water had similar fexofenadine AUC0-8 (2038±304, 2259±367, 2128±410, 1954±138 ng.h/mL; p>0.05; mean±SEM) and Cmax (440±73, 513±96, 523±104, 453±32 ng/mL; p>0.05), respectively. These four groups all had higher fexofenadine AUC0-8 (1063±59; p<0.01) and Cmax (253±18; p<0.05) compared with those for healthy individuals receiving grapefruit juice. Coeliac groups had a positive linear trend between disease severity and fexofenadine Tmax (2.0±0.3, 2.7±0.4, 3.1±0.5 hours; p<0.05). CONCLUSIONS: Coeliac disease severity based on duodenal histopathology did not affect oral fexofenadine bioavailability. Increased Tmax suggested absorption distal to the duodenum (jejunum + ileum), where histology seems more normal which may be the key determinant. Patients with coeliac disease may not require consideration for alternative clinical drug management for a number of non-metabolised and transport-mediated medications.

Clinical, Endoscopic, and Radiological Effectiveness of Ustekinumab in Bio-naïve Versus Bio-experienced Patients With Crohn's Disease: Real-world Experience From a Large Canadian Center.

INTRODUCTION: With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn's disease (CD) treated with ustekinumab in a large Canadian IBD center. METHODS: A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing. RESULTS: A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed ≥2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index ≤4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naïve patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naïve vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naïve patients. CONCLUSION: In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naïve subjects across a range of end points.

In this large real-world study of patients with Crohn's Disease treated with ustekinumab, we observed high rates of clinical, endoscopic, radiological, and biochemical response and remission rates. Effectiveness was greater in bio-naïve compared with bio-experienced patients.

Association of Trainee Participation in Colonoscopy Procedures With Quality Metrics.

Importance: Trainees routinely participate in colonoscopy procedures, yet whether their involvement is positively or negatively associated with procedural quality is unknown because prior studies involved small number of trainees and/or supervisors, lacked generalizability, and/or failed to adjust for potential confounders. Objective: To assess the association between trainee participation and colonoscopy quality metrics. Design, Setting, and Participants: This multicenter population-based cohort study was conducted at 21 academic and community hospitals between April 1, 2017, and October 31, 2018, among consecutive adult patients undergoing colonoscopy. Procedures performed by endoscopists who did not supervise trainees were excluded. Statistical analysis was performed from April 3, 2017, to October 31, 2018. Exposure: Participation by a trainee, defined as a resident or fellow enrolled in a gastroenterology or general surgery training program. Main Outcomes and Measures: The primary outcome was the adenoma detection rate (ADR), and secondary outcomes were sessile serrated polyp detection rate (ssPDR), polyp detection rate (PDR), cecal intubation rate (CIR), and perforation rate. Results: A total of 35 499 colonoscopies (18 989 women [53.5%]; mean [SD] patient age, 60.0 [14.1] years) were performed by 71 physicians (mean [SD] time in practice, 14.0 [9.3] years); 5941 colonoscopies (16.7%) involved trainees. There were no significant differences in the ADR (26.4% vs 27.3%; P = .19), CIR (96.7% vs 97.2%; P = .07), and perforation rate (0.05% vs 0.06%; P = .82) when trainees participated vs when they did not participate, whereas the the ssPDR (4.4% vs 5.2%; P = .009) and PDR (39.2% vs 42.0%; P < .001) were significantly lower when trainees participated vs when they did not. After adjustment for potential confounders, the ADR (risk ratio [RR], 0.97; 95% CI, 0.91-1.03; P = .30), PDR (RR, 0.98; 95% CI, 0.93-1.04; P = .47), and CIR (RR, 0.93; 95% CI, 0.78-1.10; P = .38) were not associated with trainee participation, although the ssPDR remained significantly lower (RR, 0.79; 95% CI, 0.64-0.98; P = .03). Conclusions and Relevance: This study suggests that trainee involvement during colonoscopy was associated with reduced ssPDR but not other colonoscopy outcome measures. Extra care should be exercised when examining the right colon when trainees are involved.

High oncostatin M predicts lack of clinical remission for patients with inflammatory bowel disease on tumor necrosis factor α antagonists.

The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with response to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in both ulcerative colitis (UC) and Crohn's disease (CD). A retrospective cohort study was conducted in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. Clinical remission was assessed at 1-year post anti-TNF exposure in addition to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis. Patients with IBD (CD, n = 82; UC, n = 40) were assessed. In both UC and CD, mean pre-treatment OSM concentrations were significantly lower in those who achieved clinical remission at 1-year (p < 0.0001). A threshold plasma OSM concentration of 168.7 pg/ml and 233.6 pg/ml respectively separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not in CD and UC respectively (CD: area under the receiver operator characteristic curve, AUROC = 0.880, 95% CI 0.79-0.96; UC: AUROC = 0.938, 95% CI 0.87-1.00). High OSM concentrations were associated with anti-TNF discontinuation and use of rescue steroids in CD and UC. High pre-treatment OSM concentrations identify IBD patients at-risk of anti-TNF non-response at 1-year as well as other deleterious clinical outcomes.

The Tricky Trachea: Tracheitis and Mediastinitis Treated With Infliximab and Steroids in a Patient With Ulcerative Colitis.

Pulmonary extra-intestinal manifestations of inflammatory bowel disease are rare, comprising 0.21% to 0.4% of the inflammatory bowel disease population. Common symptoms include cough, chest pain, and dyspnea. Abnormal pulmonary function tests are common in these patients, with restrictive, obstructive, and diffusion capacity defects. CT scanning remains the most sensitive imaging technique to detect abnormalities. Pulmonary manifestations are diverse and include airway, parenchymal, and pleural disease. Large airway disease predominates, particularly bronchiectasis. Upper airway disease is rare but concerning for the development of acute airway compromise. To our knowledge, there are no reports of concurrent mediastinitis with tracheitis in the setting of inflammatory bowel disease. We present a case of a patient with ulcerative proctitis who experienced the development of inflammatory tracheitis and mediastinitis. Her disease responded to systemic steroids and biologic therapy. In addition to our case, we reviewed the literature and provide an approach to pulmonary complications as extra-intestinal manifestation of inflammatory bowel disease.

Severity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study.

OBJECTIVE: Severity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications. DESIGN: A phase I, open-label, single-dose, pharmacokinetic study. SETTING: London, Ontario, Canada. PARTICIPANTS: Patients with coeliac disease (n=47) with positive serology and healthy individuals (n=68). MAIN OUTCOME MEASURES: Patients with coeliac disease-upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals-oral felodipine pharmacokinetics study with water and grapefruit juice. RESULTS: Coeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0-8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p<0.05) and Cmax (3.5±0.5, 4.0±0.6, 6.4±1.1; p<0.02), respectively. Healthy subjects receiving water had lower felodipine AUC0-8 (11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice. CONCLUSIONS: Increased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity.

Presence of Melena in Obscure Gastrointestinal Bleeding Predicts Bleeding in the Proximal Small Intestine.

BACKGROUND AND AIMS: Melena is a symptom of upper gastrointestinal bleeding and usually indicates bleeding proximal to the ligament of Treitz. However, whether melena predicts bleeding in the proximal small intestine in patients with obscure gastrointestinal bleeding (OGIB) is unknown and the objective of this study. METHODS: A retrospective cohort study of consecutive patients undergoing capsule endoscopy for OGIB between July 2009 and May 2016 was conducted. Subjects were categorized based on the presence of melena, and the primary outcome was identification of a bleeding source within the proximal 2/3 of the small intestine. Multi-variable regression was performed to control for confounders. RESULTS: During the study, 288 patients met the eligibility criteria. Subjects with melena accounted for 37.1% of the cohort and were more likely to be older (mean age 66.9 vs. 63.9, p = 0.0457), take warfarin (15.1 vs. 9.4%, p = 0.0122), and have a lower 12-month hemoglobin nadir (7.3 vs. 8.3 g/dL, p = 0.0002). On crude analysis, 56.1% of patients with melena had a bleeding source within the proximal small intestine compared to 34.8% for those without (RR 1.61, 95% CI 1.24-2.09, p = 0.0004). On multi-variable analysis, the presence of melena doubled the odds of finding a bleeding site within the proximal small intestine (OR 1.97, 95% CI 1.17-3.33, p = 0.010). CONCLUSIONS: The presence of melena doubles the odds of finding a bleeding site within the proximal small intestine among patients with OGIB, and deep enteroscopy, if performed before a capsule study, should begin with an antegrade approach in these patients.

Insertion of percutaneous endoscopic gastrostomy tubes with jejunal extensions using the "wedge" technique: a novel method to prevent retrograde tube migration into the stomach.

Background and study aim In percutaneous endoscopic gastrostomy (PEG) with jejunal extension (PEGJ) procedures, retrograde migration of the jejunal extension tube into the stomach during endoscope withdrawal is a frustrating problem. We describe the novel "wedge" technique for inserting the jejunal extension tube, utilizing single-balloon enteroscopy to anchor it in place. Patients and methods Prospective 1-year study of consecutive patients undergoing PEGJ insertion at a single tertiary care center. The primary outcome was number of pyloric intubations required to place the jejunal extension tube. Secondary outcomes included success rate, time, and complications related to jejunal extension tube insertion. Results 17 patients underwent the procedure. The jejunal extension tube was inserted at the first attempt in 15 patients (88.2 %) and 2 required another pyloric intubation. Abdominal X-ray showed that all PEGJ tubes were successfully seated in the proximal jejunum. The mean (SD) time required for jejunal extension insertion was 16.9 (8.6) minutes. Two adverse events occurred due to PEG insertion although none were related to the jejunal extension insertion itself. Conclusions: The "wedge" technique is an effective and easy method for inserting a jejunal extension tube after PEG insertion.

The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease.

BACKGROUND AND AIMS: Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. METHODS: Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. RESULTS: A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p < .0001). For the remaining patients who at baseline did not have inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. CONCLUSIONS: Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.

Self-Screening for Malnutrition Risk in Outpatient Inflammatory Bowel Disease Patients Using the Malnutrition Universal Screening Tool (MUST).

BACKGROUND AND AIMS: Malnutrition is common in patients with inflammatory bowel disease (IBD) and is associated with poor outcomes. Our aim is to determine if patient self-administered malnutrition screening using the malnutrition universal screening tool (MUST) is reliable by comparing patient scores with those derived from the healthcare practitioner (HCP), the gold standard. METHODS: We conducted a prospective validation study at a tertiary Canadian academic center that included 154 adult outpatients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score followed by an independent MUST assessment performed by HCPs. The main outcome measure was chance-corrected agreement (κ) of malnutrition risk categorization. RESULTS: For patient-administered MUST, the chance-corrected agreement κ (95% confidence interval [CI]) was 0.83 (0.74-0.92) when comparing low-risk and combined medium- and high-risk patients with HCP screening. Weighted κ analysis comparing all 3 risks groups yielded a κ (95% CI) of 0.85 (0.77-0.93) between patient and HCP screening. All patients were able to screen themselves. Overall, 96% of patients reported the MUST questionnaire as either very easy or easy to understand and to complete. CONCLUSION: Self-administered nutrition screening in outpatients with IBD is valid using the MUST screening tool and is easy to use. If adopted, this tool will increase utilization of malnutrition screening in hectic outpatient clinic settings and will help HCPs determine which patients require additional nutrition support.

Follow-up of participants in the Canadian Association of Gastroenterology Scholars' Program, 2006 to 2012.

The Canadian Association of Gastroenterology (CAG) Scholars' Program (previously known as the Bright Lights Course) is designed to encourage trainees to consider a subspecialty career in gastroenterology. A formal analysis of the Scholars' Program performed in 2007 revealed that 82% of participants invited to the program pursued or were planning to pursue a career in gastroenterology. The positive results are consistent with the CAG's strategic plan of developing "the next generation of gastroenterology clinical practitioners, researchers, educators, and leaders" and to "attract, train, and retain the best and the brightest to gastroenterology". The present study was a follow-up analysis of participants in the Scholars' Program between 2006 and 2012. Although 93.1% of participants had an interest in gastroenterology before attending the Scholars' Program, the majority (68.7%) reported a greater interest in gastroenterology after the program. Similar to the study from 2007, the present study again illustrates the importance and success of the Scholars' Program in generating interest and retaining candidates in gastroenterology.

Transcutaneous bowel sonography for inflammatory bowel disease is sensitive and specific when performed in a nonexpert low-volume North American center.

OBJECTIVES: Transcutaneous bowel sonography is a nonionizing imaging modality used in inflammatory bowel disease. Although available in Europe, its uptake in North America has been limited. Since the accuracy of bowel sonography is highly operator dependent, low-volume centers in North America may not achieve the same diagnostic accuracy reported in the European literature. Our objective was to determine the diagnostic accuracy of bowel sonography in a nonexpert low-volume center. METHODS: All cases of bowel sonography at a single tertiary care center during an 18-month period were reviewed. Bowel sonography was compared with reference standards, including small-bowel follow-through, computed tomography, magnetic resonance imaging, colonoscopy, and surgical findings. RESULTS: A total of 103 cases were included for analysis during the study period. The final diagnoses included Crohn disease (72), ulcerative colitis (8), hemolytic uremic syndrome (1), and normal (22). The sensitivity and specificity of bowel sonography for intestinal wall inflammation were 87.8% and 92.6%, respectively. In the subset of patients who had complications of Crohn disease, the sensitivity and specificity were 50% and 100% for fistulas and 14% and 100% for strictures. One patient had an abscess, which was detected by bowel sonography. Abnormal bowel sonographic findings contributed to the escalation of treatment in 55% of cases. CONCLUSIONS: Bowel sonography for inflammatory bowel disease can be performed in low-volume centers and provides diagnostic accuracy for luminal disease comparable with published data, although it is less sensitive for complications of Crohn disease.

Retrospective analysis of disease association and outcome in histologically confirmed ischemic colitis.

OBJECTIVE: To identify risk factors, clinical features and complications in patients with ischemic colitis (IC). METHODS: All patients diagnosed with biopsy proven IC within a 2-year period were identified; clinical data were retrospectively collected and subsequently analyzed. RESULTS: In total, 72 IC patients with a mean age of 68 years were included in this study. Among them, 18 (25.0%) were younger than 65 years with a female predominance. One-third of the patients was found to be without vascular risk factors, and 8 patients met the criteria for irritable bowel syndrome. No history of oral contraceptives or hormonal replacement therapy use could be found among the women diagnosed with IC. Over a mean duration of follow-up of 9.5 months (range 0-65 months), the rate of recurrent disease was 16.7%, while only 2 (2.8%) patients developed extra intestinal vascular sequelae. Statistical analysis identified a history of atrial fibrillation and the use of furosemide to be the only significant predictors of a poor outcome, while coronary artery disease and chronic renal failure predicted recurrence and low platelet count predicted stricture formation. CONCLUSIONS: Although most patients with IC are elderly and have conventional vascular risk factors, it should also be considered in young patients without vascular risk factors, especially in women, who may have an atypical distribution of the disease. Severe complications and extraintestinal vascular sequelae are rare, however, residual gastrointestinal complaints and recurrent disease are relatively common and there are no reliable predictors of the outcome.

Wait times for diagnostic colonoscopy among outpatients with colorectal cancer: a comparison with Canadian Association of Gastroenterology targets.

BACKGROUND: Timely access to colonoscopy is a nationally recognized issue in Canada, with previous studies documenting significant wait times for a variety of indications. However, specific wait times for colonoscopy among patients diagnosed with colorectal cancer remain unknown. METHODS: A review of all outpatient cases of colorectal cancer diagnosed at colonoscopy in London, Ontario, in 2010 was performed. Wait times from the date of referral to colonoscopy were reviewed and compared with maximal wait times established by the Canadian Association of Gastroenterology (CAG) stratified according to indication. Cancer stage at the time of diagnosis was compared with colonoscopy wait times. RESULTS: A total of 106 colorectal cancer patients meeting the inclusion and exclusion criteria were included in the study. Forty-six per cent of patients waited longer than CAG targets, with a mean (± SD) wait time of 79 ± 101 days. Higher cancer stage was associated with shorter wait time, likely as a result of triaging. CONCLUSION: Long wait times for diagnostic colonoscopy among patients with colorectal cancer remain an issue, with a significant proportion of cases not meeting maximal CAG wait time targets.

Nonutility of routine testing of stool for ova and parasites in a tertiary care Canadian centre.

BACKGROUND: In many clinical situations, stool examinations for ova and parasites (O&P) are routine in the work-up of patients with acute or chronic diarrhea. Frequently, these tests are found to be negative for pathogens. The purpose of this study was to examine the diagnostic yield of routine stool testing for O&P in a Canadian tertiary care centre and to estimate the potential clinical benefit of a positive result. PATIENTS AND METHODS: All stool samples sent to the central microbiology laboratory at London Health Sciences Centre were reviewed over a 5-year period ending January 2010. Initial screening was done by direct antigen testing using an enzyme immunoassay (EIA) technique followed by direct microscopy for negative results where there was a high index of suspicion and for positive results to rule out any concurrent parasites not included in the EIA kit. Pathogens identified were categorized and their potential susceptibility to metronidazole was estimated. No clinical data were available, as this was purely a utilization study. RESULTS: A total of 5812 stool tests were ordered. Of these, 5681 (97.7%) were completed. The most common reasons for an incomplete test were sample leakage (n = 38) and use of the incorrect collection kit (n = 32). Direct microscopy identified white blood cells in 17% of patients with positive testing. The most common pathogen was Giardia lamblia , which was detected in 45/83 (54%) of positive specimens. Entamoeba histolytica/Entamoeba dispar was identified in 16/83 (19%) and Cryptosporidium spp. in 10/83 (12%) of positive specimens. Microorganisms not thought to be pathogenic were identified in 7/83 (8%). Direct laboratory costs independent of labor were estimated at $1836 per clinically significant organism identified. Of the 77 specimens positive for pathogenic organisms, 62 (81%) were likely to be sensitive to treatment with metronidazole. CONCLUSION: In a tertiary care centre, the diagnostic yield of routine testing of stool for O&P during the evaluation of patients with acute or chronic diarrhea is low. Most clinically significant positive results should be responsive to metronidazole, but empirical treatment is not encouraged. Strategies to identify patients with a higher likelihood of harboring pathogenic parasites and consideration of empiric metronidazole therapy for patients at highest risk merit further research.

Intestinal CYP3A4 and midazolam disposition in vivo associate with VDR polymorphisms and show seasonal variation.

Vitamin D, whose levels vary seasonally with sunlight, is activated to 1α,25-dihydroxyvitamin D(3) that binds the vitamin D receptor (VDR) and transcriptionally regulates intestinal CYP3A4 expression. We genotyped VDR polymorphisms and determined their associations with intestinal CYP3A4 and with midazolam pharmacokinetics, and whether intestinal CYP3A4 levels/activity varied seasonally. The VDR BsmIG > A (rs1544410) polymorphism was significantly associated with CYP3A4 jejunal expression/activity, with CYP3A4 duodenal mRNA, and with midazolam area under the curve (AUC). Intestinal CYP3A4 expression/activity was significantly higher in biopsies with the VDR promoter polymorphisms Cdx2-3731G > A and GATA-1012A > G that increase VDR activation of target genes. Duodenal CYP3A4 mRNA was significantly higher between April and September than between October and March. Midazolam p.o. AUC and oral bioavailability trended higher October through March compared to April through September. These data suggest VDR polymorphisms are predictors of intestinal CYP3A4, and that CYP3A4 intestinal expression varies seasonally--likely related to annual changes in UV sunlight and vitamin D levels.