Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Background: Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. Objectives: This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Design: Retrospective consecutive patient cohort analysis. Methods: We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. Results: During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. Conclusion: EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.

Outcome and approach of small-bowel stricture dilation using balloon-assisted endoscopy in patients with Crohn's disease This study investigated the safety and success of using balloon-assisted endoscopy as a method to dilate small bowel strictures in patients with Crohn's disease. As a secondary outcome, we compared the overall safety and success between two different types of endoscopic systems: the single- and double-balloon systems.

The Effect of an Electronic Medical Record-Based Clinical Decision Support System on Adherence to Clinical Protocols in Inflammatory Bowel Disease Care: Interrupted Time Series Study.

Background: Clinical decision support systems (CDSSs) embedded in electronic medical records (EMRs), also called electronic health records, have the potential to improve the adoption of clinical guidelines. The University of Alberta Inflammatory Bowel Disease (IBD) Group developed a CDSS for patients with IBD who might be experiencing disease flare and deployed it within a clinical information system in 2 continuous time periods. Objective: This study aims to evaluate the impact of the IBD CDSS on the adherence of health care providers (ie, physicians and nurses) to institutionally agreed clinical management protocols. Methods: A 2-period interrupted time series (ITS) design, comparing adherence to a clinical flare management protocol during outpatient visits before and after the CDSS implementation, was used. Each interruption was initiated with user training and a memo with instructions for use. A group of 7 physicians, 1 nurse practitioner, and 4 nurses were invited to use the CDSS. In total, 31,726 flare encounters were extracted from the clinical information system database, and 9217 of them were manually screened for inclusion. Each data point in the ITS analysis corresponded to 1 month of individual patient encounters, with a total of 18 months of data (9 before and 9 after interruption) for each period. The study was designed in accordance with the Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI) guidelines for health informatics evaluations. Results: Following manual screening, 623 flare encounters were confirmed and designated for ITS analysis. The CDSS was activated in 198 of 623 encounters, most commonly in cases where the primary visit reason was a suspected IBD flare. In Implementation Period 1, before-and-after analysis demonstrates an increase in documentation of clinical scores from 3.5% to 24.1% (P<.001), with a statistically significant level change in ITS analysis (P=.03). In Implementation Period 2, the before-and-after analysis showed further increases in the ordering of acute disease flare lab tests (47.6% to 65.8%; P<.001), including the biomarker fecal calprotectin (27.9% to 37.3%; P=.03) and stool culture testing (54.6% to 66.9%; P=.005); the latter is a test used to distinguish a flare from an infectious disease. There were no significant slope or level changes in ITS analyses in Implementation Period 2. The overall provider adoption rate was moderate at approximately 25%, with greater adoption by nurse providers (used in 30.5% of flare encounters) compared to physicians (used in 6.7% of flare encounters). Conclusions: This is one of the first studies to investigate the implementation of a CDSS for IBD, designed with a leading EMR software (Epic Systems), providing initial evidence of an improvement over routine care. Several areas for future research were identified, notably the effect of CDSSs on outcomes and how to design a CDSS with greater utility for physicians. CDSSs for IBD should also be evaluated on a larger scale; this can be facilitated by regional and national centralized EMR systems.

An intriguing vision for transatlantic collaborative health data use and artificial intelligence development.

Our traditional approach to diagnosis, prognosis, and treatment, can no longer process and transform the enormous volume of information into therapeutic success, innovative discovery, and health economic performance. Precision health, i.e., the right treatment, for the right person, at the right time in the right place, is enabled through a learning health system, in which medicine and multidisciplinary science, economic viability, diverse culture, and empowered patient's preferences are digitally integrated and conceptually aligned for continuous improvement and maintenance of health, wellbeing, and equity. Artificial intelligence (AI) has been successfully evaluated in risk stratification, accurate diagnosis, and treatment allocation, and to prevent health disparities. There is one caveat though: dependable AI models need to be trained on population-representative, large and deep data sets by multidisciplinary and multinational teams to avoid developer, statistical and social bias. Such applications and models can neither be created nor validated with data at the country, let alone institutional level and require a new dimension of collaboration, a cultural change with the establishment of trust in a precompetitive space. The Data for Health (#DFH23) conference in Berlin and the Follow-Up Workshop at Harvard University in Boston hosted a representative group of stakeholders in society, academia, industry, and government. With the momentum #DFH23 created, the European Health Data Space (EHDS) as a solid and safe foundation for consented collaborative health data use and the G7 Hiroshima AI process in place, we call on citizens and their governments to fully support digital transformation of medicine, research and innovation including AI.

A novel smartphone application for the tracking of procedural numbers and trainee experience in gastrointestinal endoscopy.

OBJECTIVES: The tracking and documentation of procedures in gastrointestinal endoscopy including therapeutic interventions is an essential but challenging process. The University of Alberta has developed a smartphone app to help facilitate this task. This study evaluated the functionality, usefulness, and user satisfaction of this app. METHODS: Four Gastroenterology (GI) residents and two therapeutic endoscopy fellows participated in the study. The trainees submitted all their data into the app from the procedures in which they participated hands-on for one year, data was collected and analyzed on the app and the website associated with it. RESULTS: Trainees were able to register the procedures immediately after each procedure without difficulty, this data was available to be reviewed at anytime in the app and associated website. Furthermore, the data collected was able to be transformed into tables and graphs on the app website. The total number of procedures and therapeutic interventions performed were easily accessed in the app and website at anytime. The app facilitated the calculation of the cecal intubation rate in colonoscopy and the cannulation rate in ERCP for the therapeutic endoscopy trainee. Trainees reported excellent experience with the app capabilities. CONCLUSIONS: A novel smartphone app was useful in collecting meaningful data submitted by gastrointestinal endoscopy trainees, furthermore, through an associated website, it was capable to create graphs and tables to show and facilitate the calculation of meaningful data such as key performance indicators.

Clostridium difficile Infection in Patients with Ulcerative Colitis Treated with Tofacitinib in the Ulcerative Colitis Program.

BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Patients with inflammatory bowel disease are susceptible to Clostridium difficile infection (CDI). Here, we evaluate CDI in the tofacitinib UC clinical program. METHODS: Events from 4 randomized, placebo-controlled studies (phase [P] 2 or P3 induction [NCT00787202; NCT01465763; NCT01458951], P3 maintenance [NCT01458574]) and an open-label, long-term extension (OLE) study (NCT01470612), were analyzed as 3 cohorts: Induction (P2/P3 induction), Maintenance (P3 maintenance), and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, and OLE studies; including final data from the OLE study, as of August 24, 2020). Proportions and incidence rates (unique patients with events per 100 patient-years of exposure) of CDI were evaluated. RESULTS: The overall cohort comprised 1157 patients who received ≥1 dose of tofacitinib 5 or 10 mg BID, with a total of 2814.4 patient-years of tofacitinib exposure and up to 7.8 years of treatment. A total of 82.6% of patients received predominantly tofacitinib 10 mg BID. In the induction, maintenance, and overall cohorts, 3 (2 tofacitinib treated, 1 placebo treated), 3 (all placebo treated), and 9 patients had CDI, respectively; the overall cohort incidence rate was 0.31 (95% confidence interval, 0.14-0.59). CDI were all mild-moderate in severity and resolved with treatment in 8 patients. Six of 9 patients continued tofacitinib treatment without interruption. Two patients had events reported as serious due to hospitalization. Two patients were receiving corticosteroids when the CDI occurred. CONCLUSION: CDIs among patients with UC receiving tofacitinib were infrequent, cases were mild-moderate in severity, and most resolved with treatment.

The incidence of Clostridium difficile infection in the tofacitinib ulcerative colitis clinical program was evaluated. C. difficile infection among patients with ulcerative colitis receiving tofacitinib were infrequent; cases were mild­moderate in severity, and most resolved with treatment.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Declining Corticosteroid Use for Inflammatory Bowel Disease Across Alberta: A Population-Based Cohort Study.

Background and Aims: Corticosteroid-free remission is a primary treatment goal in IBD which may be achieved with greater use of anti-TNF therapy. We defined temporal trends of corticosteroid use, anti-TNF use, hospitalization and surgery in a prevalent IBD cohort within the province of Alberta, Canada. Methods: Health administrative data were used to identify medication dispensing, hospitalizations and surgery in individuals with IBD from 2010 to 2015. Temporal trends were calculated using log-binomial regression for medications and log-linear models for hospitalizations and surgery rates. Analyses were stratified based on geographic location. Results: Of 28890 individuals with IBD, 50.3% had Crohn's disease. One in six individuals (15.45%) were dispensed a corticosteroid. Corticosteroid use decreased in both metropolitan areas (AAPC -20.08%, 95% CI: -21.78 to -18.04) and non-metropolitan areas (AAPC -18.14%, 95% CI: -20.78 to -18.04) with a similar pattern for corticosteroid dependence. Corticosteroid dependence was more prevalent in UC vs. CD (P < 0.05), and in the pediatric IBD cohort (13.45) compared to the adult (8.89) and elderly (7.54) cohorts (per 100 prevalent population, P < 0.001). The proportion of individuals dispensed an anti-TNF increased over the study period (AAPC 12.58%, 95% CI: 11.56 to 13.61). Significantly more non-metropolitan versus metropolitan residing individuals were hospitalized for any reason, for an IBD-related, or IBD-specific indication (all P < 0.001) though the proportion requiring IBD surgery was similar between groups. Conclusions: An increase in anti-TNF use corresponded to a decline in corticosteroid use and dependence in those with IBD. Inequities in IBD care still exist based on location and age.

A randomized controlled trial of a multicomponent online stress reduction intervention in inflammatory bowel disease.

Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design. Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD. Design: This is a RCT. Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2-3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen's Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences. Results: Of 150 screened patients, 101 were randomized to the intervention (n = 49) and control (n = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn's disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5-34.3, p < 0.001). Significant improvements were seen in mental health, resilience, and HRQoL measures, with a median satisfaction score of 89/100 at the end of the 12 weeks. In the 44/49 patients who completed the intervention, 91% achieved program adherence targets. Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course. Registration: ClinicalTrials.gov Identifier NCT03831750. Plain Language Summary: An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2-3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention.

[Position paper on reporting of intestinal ultrasound findings in patients with inflammatory bowel disease]. / Positionspapier zur Befunderhebung von Darmultraschallbefunden bei chronisch entzündlichen Darmerkrankungen.

BACKGROUND: Intestinal ultrasound is increasingly used for primary diagnosis, detection of complications and monitoring of patients with Crohn's disease and ulcerative colitis. Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different specialties. The current manuscript describes the features required for optimized reporting of intestinal ultrasound findings in inflammatory bowel disease (IBD). METHODS: An expert consensus panel of gastroenterologists, radiologists, pathologists, paediatric gastroenterologists and surgeons conducted a systematic literature search. In a Delphi- process members of the Kompetenznetz Darmerkrankungen in collaboration with members of the German Society for Radiology (DRG) voted on relevant criteria for reporting of findings in intestinal ultrasound. Based on the voting results statements were agreed by expert consensus. RESULTS: Clinically relevant aspects of intestinal ultrasound (IUS) findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images. CONCLUSION: The current manuscript provides practical recommendations on how to standardize documentation and reporting from intestinal ultrasound findings in patients with IBD.

Artificial intelligence enabled automated diagnosis and grading of ulcerative colitis endoscopy images.

Endoscopic evaluation to reliably grade disease activity, detect complications including cancer and verification of mucosal healing are paramount in the care of patients with ulcerative colitis (UC); but this evaluation is hampered by substantial intra- and interobserver variability. Recently, artificial intelligence methodologies have been proposed to facilitate more objective, reproducible endoscopic assessment. In a first step, we compared how well several deep learning convolutional neural network architectures (CNNs) applied to a diverse subset of 8000 labeled endoscopic still images derived from HyperKvasir, the largest multi-class image and video dataset from the gastrointestinal tract available today. The HyperKvasir dataset includes 110,079 images and 374 videos and could (1) accurately distinguish UC from non-UC pathologies, and (2) inform the Mayo score of endoscopic disease severity. We grouped 851 UC images labeled with a Mayo score of 0-3, into an inactive/mild (236) and moderate/severe (604) dichotomy. Weights were initialized with ImageNet, and Grid Search was used to identify the best hyperparameters using fivefold cross-validation. The best accuracy (87.50%) and Area Under the Curve (AUC) (0.90) was achieved using the DenseNet121 architecture, compared to 72.02% and 0.50 by predicting the majority class ('no skill' model). Finally, we used Gradient-weighted Class Activation Maps (Grad-CAM) to improve visual interpretation of the model and take an explainable artificial intelligence approach (XAI).

Ustekinumab Exposure in Pregnant Women From Inflammatory Bowel Disease Clinical Trials: Pregnancy Outcomes Through Up To 5 Years in Crohn's Disease and 2 Years in Ulcerative Colitis.

Background: While no adverse developmental outcomes were observed in preclinical animal studies, limited data exist regarding effects of ustekinumab on human pregnancies. Previously, no data have been reported for women treated with ustekinumab in inflammatory bowel disease (IBD) clinical trials and corresponding pregnancy outcomes. Here, we present pregnancy outcomes from IBD clinical trials, incorporating 5 years of treatment in Crohn's disease (CD) and 2 in ulcerative colitis (UC). Methods: All patients in the clinical trials agreed to use adequate birth control and were discontinued from treatment upon pregnancy confirmation. Nonetheless, 39 pregnancies occurred with maternal ustekinumab exposure from 4 CD and 1 UC study. Maternal and neonatal outcomes and data are presented with summary statistics, where available. Results: Of 1289 women who received ≥1 dose of ustekinumab, 39 maternal pregnancies with outcomes were reported (pregnancy cohort). Median maternal age was 28.0 years and median duration of ustekinumab treatment before pregnancy was 63.7 weeks with the last dose of ustekinumab administered prior to or during the first trimester (terminal half-life of ~3 weeks). Outcomes for the 39 pregnancies were: 26 live births (all normal newborns), 8 spontaneous abortions, and 5 elective abortions. No congenital anomalies were reported among normal newborns and no safety signals emerged with neonatal outcomes. Conclusions: Based on this series of 39 pregnancies with outcomes from IBD clinical trials, mothers treated with ustekinumab (limited to up to the first trimester) did not demonstrate a risk of negative outcomes. More data are needed to characterize the safety profile of ustekinumab use during pregnancy.

Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population-based cohort study.

BACKGROUND: Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab. AIMS: To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life METHODS: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3). Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance. RESULTS: In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring. CONCLUSIONS: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.

[Position paper on endoscopic reporting in IBD]. / Positionspapier zur Befunderstellung endoskopischer Untersuchungen bei Patienten mit chronisch-entzündlichen Darmerkrankungen.

The complete and reliable documentation of endoscopic findings make up the crucial foundation for the treatment of patients with inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. These findings are, on the one hand, a prerequisite for therapeutic decisions and, on the other hand, important as a tool for assessing the response to ongoing treatments. Endoscopic reports should, therefore, be recorded according to standardized criteria to ensure that the findings of different endoscopists can be adequately compared and that changes in the course of the disease can be traced back. In consideration of these necessities, fifteen members of the Imaging Working Group of the German Kompetenznetz Darmerkrankungen have created a position paper proposing a structure and specifications for the documentation of endoscopic exams. In addition to the formal report structure, the recommendations address a large number of attributes of acute and chronic inflammatory alterations as well as endoscopically detectable complications, which are explained in detail and illustrated using exemplary images. In addition, more frequently used endoscopic activity indices are presented and their use in everyday clinical practice is discussed.

Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme.

BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. METHODS: Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. RESULTS: In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death. CONCLUSIONS: During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.

Concomitant 5-Aminosalicylate Therapy in Moderate-to-Severe Ulcerative Colitis Patients Escalated to Infliximab Is Not Beneficial.

BACKGROUND AND AIMS: While there is recent literature to support the discontinuation of 5-aminosalicylate (5-ASA) upon the initiation of biologics, continuing 5-ASA after treatment failure is relatively common. We aimed to assess the impact of concomitant 5-ASA therapy on clinical outcomes in ulcerative colitis (UC) patients escalated to infliximab. METHODS: This is a retrospective chart review of patients with moderate-to-severe UC started on infliximab between January 2012 and December 2017 at the University of Alberta. The primary outcome was clinical remission (partial Mayo score < 2) at 6 and 12 months. Secondary outcomes included endoscopic (endoscopic Mayo < 2) and deep remission (combined clinical and endoscopic remission) as well as the need for rescue therapy, hospitalization or colectomy. Univariate and multivariate logistic regression models were used to estimate the odds ratios and 95% CI for the outcomes. RESULTS: One hundred and twenty-one patients were followed over a period of 47 (SD = 34) months. Patients on 5-ASA had increased concomitant immunomodulator use (73.3% vs. 54.1%, p = 0.03). There was no difference in clinical remission at 6 (aOR 2.59, p = 0.07) or 12 months (aOR 0.43, p = 0.06). At 12 months, patients on concomitant 5-ASA were less likely to achieve endoscopic (aOR 0.08, p = 0.01) and deep remission (aOR 0.07, p = 0.02). Adverse outcomes such as need for rescue therapy, hospitalization, and colectomy did not differ between the groups. CONCLUSIONS: Our data suggest that 5-ASA may be stopped in patients with moderate-to-severe UC who have been escalated to infliximab therapy as it has no additional benefit to control inflammation.

Digital advantage in the COVID-19 response: perspective from Canada's largest integrated digitalized healthcare system.

The SARS-CoV-2 pandemic has challenged healthcare systems worldwide. Uncertainty of transmission, limitations of physical healthcare system infrastructure and supplies as well as workforce shortages require dynamic adaption of resource deployment to manage rapidly evolving care demands, ideally based on real time data for the entire population. Moreover, shut down of traditional face-to-face care infrastructure requires rapid deployment of virtual health care options to avoid collapse of health organizations. The Alberta Electronic Health Record Information System is one of the largest population based comprehensive electronic medical record (EMR) installations. Alberta's long standing solid telehealth hardware-, training-, provider remuneration- and legislation infrastructure has enabled quick transition to virtual healthcare. Virtual health services including asynchronous secure clinical communications, real-time virtual care via messaging, telephony or video conferencing (telehealth) and ancillary functions like triage, scheduling, documentation and reporting, the previously established virtual hospital program with home monitoring, virtual health assessments, medication review, education and support for patients and families and coordination between family doctors, specialists and other health team members help to control viral transmission, protect healthcare personnel and save supplies. Moreover, rapid launch of online screening and triage tools to guide testing and isolation, online result sharing, infected patient and contact tracing including a smartphone exposure tracking application (ABTraceTogether), electronic best practice alerts and decision support tools, test and treatment order sets for standardized COVID-19 management, continuous access to population level real-time data to inform healthcare provider, public health and government decisions have become key factors in the management of a global crisis in Alberta.

Darvadstrocel for the treatment of perianal fistulas in Crohn's disease.

INTRODUCTION: Perianal fistulizing Crohn's disease is associated with a poor quality of life and current medical and surgical treatment options are limited. Darvadstrocel, composed of mesenchymal stem (stromal) cells (MSC), has recently been approved by the European Medicines Agency (EMA) for the treatment for perianal disease. This drug profile educates the reader with this novel treatment approach. AREAS COVERED: A literature search was performed on PubMed with focus on perianal fistulizing Crohn's disease and mesenchymal stem (stromal) cells. This review summarizes evidence of the current standard of care and discusses the mechanism of action, manufacturing, and application and safety of darvadstrocel. EXPERT OPINION: Darvadstrocel is a safe and effective therapy for complex perianal fistulizing Crohn's disease.

Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention, and Management.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

An overview of clinical decision support systems: benefits, risks, and strategies for success.

Computerized clinical decision support systems, or CDSS, represent a paradigm shift in healthcare today. CDSS are used to augment clinicians in their complex decision-making processes. Since their first use in the 1980s, CDSS have seen a rapid evolution. They are now commonly administered through electronic medical records and other computerized clinical workflows, which has been facilitated by increasing global adoption of electronic medical records with advanced capabilities. Despite these advances, there remain unknowns regarding the effect CDSS have on the providers who use them, patient outcomes, and costs. There have been numerous published examples in the past decade(s) of CDSS success stories, but notable setbacks have also shown us that CDSS are not without risks. In this paper, we provide a state-of-the-art overview on the use of clinical decision support systems in medicine, including the different types, current use cases with proven efficacy, common pitfalls, and potential harms. We conclude with evidence-based recommendations for minimizing risk in CDSS design, implementation, evaluation, and maintenance.