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Background Data on the association of ustekinumab (UST) drug concentrations and clinical outcomes are conflicting. We assessed serum UST drug and anti-UST antibody concentrations using three commercially available assays. Methods Sixty-one blood samples were analyzed for serum UST drug and anti-UST antibody concentrations using three assays: one homogeneous mobility shift assay (HMSA, Prometheus, Assay A), and two enzyme-linked immunosorbent assays (ELISA; Progenika, Dynacare, Assay B and Theradiag, Assay C). Results The median (IQR) serum UST concentrations for the three assays were: Assay A 7.50 (5.35 to 12.88) µg/mL, Assay B 4.02 (2.46 to 6.95) µg/mL and Assay C 4.35 (2.62 to 7.50) µg/mL. A Kruskal–Wallis test confirmed a statistically significant difference between the different assays, X2(2) = 30.606, p < 0.001. Linear regression showed near twofold increased difference in the absolute drug concentrations between the HMSA and either ELISA. Linear quantitative correlation was observed for all three assays (r = 0.836 for A versus B, r = 0.792 for A versus C, r = 0.936 for B versus C; p < 0.01). The intraclass correlation coefficient (ICC) between assay A and B was 0.649 (95% confidence interval [CI] −0.208 to 0.874); assay A and C was 0.671 (95% CI −0.165 to 0.878); and assay B and C was 0.958 (95% CI 0.928 to 0.975); p < 0.001. No anti-UST antibodies were detected. Conclusion A good correlation was observed for serum UST drug concentrations and a good agreement was observed between the ELISA tests. However, agreement was poor between the HMSA and each ELISA tests. Clinical recommendations regarding drug concentrations should be based on assay type used.

Background and study aim  Few scales assessing bowel preparation quality have been validated, and direct between-scale comparisons remain scarce. The aim of the study was to compare inter- and intra-rater reliability, predictive abilities for clinical outcomes, and ease of use for each scale. Methods  Colonoscopy video recordings highlighting five colonic segments after washing were viewed independently by three physicians, and cleanliness was evaluated using the Boston Bowel Preparation Scale (BBPS), the Chicago Bowel Preparation Scale (CBPS), and the Harefield Cleansing Scale (HCS) in randomized order. Kappa or intraclass correlations quantified intra- and inter-rater reliability. Ease of use was evaluated (1 – 10 scale, 1 = easy), as were associations between scores, adenoma detection, and adequacy of preparation to exclude lesions ≥ 5 mm. Results  Among 83 colonoscopy videos, indications included screening or surveillance in 72.3 %. Mean (± SD) scores of the respective three raters were 5.17 ± 1.57, 6.49 ± 1.48, and 5.12 ± 1.21 for BBPS, and 23.73 ± 6.01, 28.39 ± 5.47, and 24.75 ± 5.83 for CBPS, while successful HCS scores (grade A or B) were given for 76 %, 89 %, and 63 % of examinations. Intra-rater reliability ranges were 0.88 – 1.00, 0.83 – 1.00, and 0.62 – 1.00 for BBPS, CBPS, and HCS, respectively. Similarly, inter-rater reliability ranges were 0.50 – 0.79, 0.64 – 0.83, and 0.28 – 0.52, respectively. Sources of disagreement included varying rater strictness, which was possibly most marked for preparations rated as intermediate. Overall, associations between preparation scores and adenoma detection lacked statistical significance. Conclusion  The BBPS and CBPS showed the best inter- and intra-rater reliability, and the BBPS was considered the easiest to use. Further studies are needed to determine an optimal adequacy threshold for these scales, with the goal of predicting clinical outcomes and determining the appropriate interval to the next colonoscopy.

Background The medical treatment of fistulizing Crohn’s disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD. Methods We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI). Results In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55). Conclusions Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.

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Background Existing bowel preparation scales (BPS) only modestly predict interval to next colonoscopy. The US Multi-Society Task Force (MSTF) recommends repeating colonoscopies within the year if the preparation does not allow detection of polyps over 5 mm. Aim This study aims to assess reliability and validity of an auditable application of the MSTF compared with the Boston BPS (BBPS). Methods We compared an auditable application of MSTF guidelines termed the Montreal BPS (MBPS) with the BBPS using a total cut-off score ≥6 with each segment score ≥2 (BBPS2-6). In sensitivity analyses, we applied the MBPS using a cut-off of 3 mm rather than 5 mm and also assessed the BBPS using an adequacy threshold of total score ≥5 (BBPS5). Videos of 83 colonoscopies (eight for intra-rater agreements) were independently evaluated by nine physicians. Weighted kappas quantified intra- and inter-rater agreements. Associations between scores and clinical outcomes were assessed. Results The BBPS2-6 and 5 mm MBPS showed moderate to substantial intra-rater agreements (κ=0.44 to 0.63 and κ=0.50 to 0.53, respectively); inter-rater agreements were only fair to moderate and slight to moderate (κ=0.25 to 0.48 and κ=0.19 to 0.50, respectively). Similar results were noted using alternate thresholds of BBPS5 and 3 mm MBPS. No significant associations were found between scores and clinical outcomes. Conclusion For all scales, intra-rater kappas were superior to inter-rater values, the latter reflecting at best moderate agreement. This modest performance may reflect the dichotomized interpretation of the scales (adequate versus inadequate), differing from previous publications assessing scores as continuous variables. Further studies are required to optimally interpret bowel preparation scales with regard to interval to next colonoscopy.

Background Sedation practices vary widely by region. In Canada, endoscopist-directed administration of a combination of fentanyl and midazolam is standard practice. A minority of cases are performed with propofol. Aims To describe the safety of nonanaesthetist administered low-dose propofol as an adjunct to standard sedation. Methods This was a single-centre retrospective study of patients having undergone endoscopic procedures with propofol sedation between 2004 and 2012 in a teaching hospital in Montreal. Procedures were performed by gastroenterologists trained in Advanced Cardiovascular Life Support. Sedation was administered by intravenous bolus by a registered nurse, under the direction of the endoscopist. Outcomes of procedures were collected in the context of a retrospective chart review using the hospital’s endoscopy database. Results Of patients undergoing endoscopies at our centre, 4930 patients received propofol as an adjunct to standard sedation with fentanyl and midazolam. Cecal intubation rate for colonoscopies (n = 2921) was 92.0%. Gastroscopies (n = 1614), flexible sigmoidoscopies (n = 28), endoscopic retrograde cholangiopancreatography (n = 331) and percutaneous endoscopic gastrostomy insertion (n = 36) had success rates, defined as successful completion of the procedure within anatomical limits, of 99.0, 96.4, 94.0 and 91.7%, respectively. The average dose of propofol used for each procedure was 34.5 ± 20.8 mg. Fentanyl was used in 67.4% of procedures at an average dose of 94.3 ± 17.5 mcg. Midazolam was used in 92.7% of cases at an average dose of 3.0 ± 0.7 mg. Reversal agents (naloxone or flumazenil) were used in 0.43% of the cases (n = 21). Patients who received propofol were discharged uneventfully within the usual postprocedure recovery time. One patient required sedation-related hospitalization. For patients having received propofol in addition to standard sedation agents, 99.6% experienced no adverse events. There were no mortalities. Conclusion The use of low-dose propofol as an adjunct to fentanyl and midazolam, administered by a registered nurse under the direction of the endoscopist was safe and effective in patients at our centre.

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