The impact of source and consumption of news on mental distress among inflammatory bowel disease patients during the COVID-19 pandemic.

Background: We sought to understand the trends in media use, and how consumption and source affected mental health of persons with inflammatory bowel disease during the early parts of the pandemic. Dissemination of news during the coronavirus disease 2019 (COVID-19) pandemic was integral to educating the public but also could be harmful if constantly consumed, leading to worsening anxiety. Methods: We performed a survey study in autumn 2020 during the second wave of COVID-19 in Manitoba. The survey included questions on consumption of COVID-19 news, along with validated measures of perceived stress, generalized anxiety, health anxiety, and depression. We used multivariable logistic regression analysis to assess trusted sources of news as a predictor of clinically significant mental health symptoms. Results: Of the 2940 participants in the registry, 1384 (47.1%) persons responded. The most trusted sources of news were television (64.2%), internet (46.1%), newspaper (27.6%), friends/family (21.7%), social media (16.9%), and radio (16.6%). Those who trusted social media had higher odds of depression (aOR 1.52, 95%CI 1.04-2.22), and perceived stress (aOR 2.56, 95%CI 1.09-2.21). Persons who reported extreme difficulty limiting their time-consuming news about COVID-19 and who spent more than 1 h daily consuming information on COVID-19 both had increased odds of any clinically significant mental health symptoms. Conclusions: It is unknown if consumption of COVID-19 news led to heightened mental health symptoms or if increasing anxieties and concerns led to consuming more news. Further research is needed to assess whether these elevated mental health symptoms led to worse disease outcomes.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

How Did COVID-19 Affect Mental Health and Access to Care in Persons With Inflammatory Bowel Disease.

The coronavirus disease pandemic globally affected public health and the world economy, leading to an increase in mental health symptoms, thought to be due in part to periods of quarantining, restrictions, and other interventions used to curb ongoing transmission of the virus. It is well established that persons with inflammatory bowel disease (IBD) have significantly higher rates of depression and anxiety than the general population and that mental health symptoms can exacerbate disease severity. For persons with IBD, psychological distress was correlated with challenges in accessing medical care. In the early stages of the pandemic, endoscopy suites were closed, leading to fewer colonoscopies, although this rebounded the following year. This likely led to fewer diagnoses of IBD initially as people avoided the health care system, and also a reduction in IBD-related dysplasia being detected during colonoscopy. Many hospitals and health care clinics adjusted by delivering telemedicine for ambulatory care. Persons with IBD had increased stress about accessing both their health care provider and gastroenterologist during the pandemic, although many had increased satisfaction with the level of care they received virtually. Telemedicine is now being used in most clinics in conjunction with in-person care, to help deliver care, and can be cost-effective. Additional research is needed to assess whether heightened levels of mental health symptoms have led to worsening disease activity, and further, if a delay in health care access including colonoscopies and surgeries, or the perceived decreased access to health care professionals for some will have detrimentally affected the disease course for persons with IBD.

The Impact of COVID-19 on Health Anxiety and Perceived Stress Among Persons with IBD: A Population-representative Study.

Background: The Corona Virus Immune Disease-2019 (COVID-19) pandemic has broadly impacted the mental health of individuals worldwide, especially with restrictions including social distancing and quarantining. Persons with IBD are at increased risk of mental health disorders. The aim was to understand how the COVID-19 pandemic affected adults with a chronic health issue, inflammatory bowel disease (IBD), using a population-based sample. Methods: A survey study in Manitoba was conducted during the second COVID-19 wave in autumn 2020. We assessed proportions of health anxiety and perceived stress using validated measures, as well as stressors during the COVID-19 pandemic. We used univariable and multivariable logistic regression analysis to assess predictors of perceived stress and health anxiety. Results: A total of 1,384 (47.1%) persons responded, with a mean age of 58.0, and 46.9% had Crohn's disease. Almost three quarters (73.7%) had increased stress, with 37.7% having increased stress about their IBD, and 33.6% worried about their IBD worsening. 46.0% felt increased stress about accessing their doctor or nurse, and 56.5% felt they had good access to their gastroenterologist. Elevated stress and health anxiety were seen in 63.5% and 17.2% of respondents, respectively. Younger age and being on immune-modifying therapy (IMT) was predictive of increased health anxiety and stress. Longer IBD duration was associated with decreased stress, including those on IMT. Conclusion: Persons with IBD reported high rates of stress and health anxiety early in the COVID-19 pandemic, especially among those on IMT. It will be important to determine how this evolved over time and to what extent this impacted on disease course.

OPTIMIZING TIMING OF FOLLOW-UP COLONOSCOPY: A PILOT CLUSTER RANDOMIZED TRIAL OF A KNOWLEDGE TRANSLATION TOOL.

BACKGROUND: Endoscopists have low adherence to guideline recommended colonoscopy surveillance intervals. We performed a cluster randomized single-blind pilot trial in Winnipeg, Canada to assess the effectiveness of a newly developed digital application tool which computes guideline recommended follow-up intervals. METHODS: Participant endoscopists were randomized to either receive access to the digital application (intervention group) or not receive access (control group). Pathology reports and final recommendations for colonoscopies performed in the 1-4 months before randomization and 3-7 months post-randomization were extracted. Generalized estimating equation models were used to determine if the access to the digital application predicted guideline congruence. RESULTS: We included 15 endoscopists in the intervention group and 14 in the control group (out of 42 eligible endoscopists in the city), with 343 patients undergoing colonoscopy before randomization, and 311 post-randomization. Endoscopists who received the application made guideline-congruent recommendations 67.6% of the time prior to randomization and 76.1% of the time after randomization. Endoscopists in the control group made guideline- congruent recommendations 72.4% and 72.9% of the time pre- and post-randomization, respectively. Endoscopists in the intervention group trended to have an increase in guideline adherence comparing post to pre-intervention (OR:1.50, 95%CI 0.82-2.74). In contrast, the control group had no change in guideline adherence (OR:1.07, 95%CI 0.50-2.29). Endoscopists in the intervention group with less than median guideline congruence pre-randomization had a significant increase in guideline congruent recommendations post-randomization. CONCLUSION: An application that provides colonoscopy surveillance intervals may help endoscopists with guideline congruence, especially those with a lower pre-intervention congruence with guideline recommendations. (ClincialTrials.gov number, NCT04889352).

The Association Between Increased Maladaptive Health Behaviours and Elevated Mental Health Symptoms Among Persons with IBD During the COVID-19 Pandemic.

Aim: To assess the association between maladaptive health behaviours and elevated mental health (MH) symptoms during the COVID-19 pandemic among persons with inflammatory bowel disease (IBD). Methods: Participants of the population-based University of Manitoba IBD Research Registry (n = 2,942) were invited to participate in a survey in November 2020, regarding their experiences during the COVID-19 pandemic. Maladaptive health behaviours included increased use of alcohol, marijuana, and cigarettes, and reduced exercise relative to pre-pandemic levels. Clinically significant MH symptoms were defined by the presence of elevated anxiety, depression, and/or post-traumatic stress. Adjusted logistic regression assessed the odds of elevated MH symptoms predicted by maladaptive health behaviours, stratified by gender. Results: Of 1,363 (46%) respondents, 319 (23%) had elevated MH symptoms. Those with elevated MH symptoms were older (mean age 54) and predominantly females (70%). The odds of any elevated MH symptoms were approximately two to four times greater among those who experienced maladaptive health behaviours during the pandemic including: increased alcohol use [aOR 2.14, 95% CI (1.50-3.05)], males who increased marijuana use [aOR 4.18, 95% CI (1.18-14.74)], females who increased smoking cigarettes [aOR 3.68 95% CI (1.15-11.86)] and any maladaptive health behaviour [aOR 1.93 95% CI (1.44-2.60)]. Conclusion: During the COVID-19 pandemic, persons with IBD who experienced any maladaptive health behaviour was associated with double the likelihood of experiencing clinically significant MH symptoms. For persons with elevated MH symptoms, it is important for health care providers to recognize the association of increased maladaptive behaviours. Alternatively, if it is determined that MH symptoms predated maladaptive health behaviours then, inquiries into MH and providing appropriate referrals should be pursued.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-IBD in Seniors.

Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn's disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider. Treatment of the elderly is similar to younger persons with IBD, though considerations of the increased risk of infections and malignancy must be considered when using immune modulating drugs. Whether anti-TNF therapies increase the risk of infections is not definitive, though newer biologics, including vedolizumab and ustekinumab, are thought to be safer with lower risk of adverse events. Polypharmacy and frailty are other considerations in the elderly when choosing a treatment, as frailty is associated with worse outcomes. Costs for IBD-related hospitalizations are higher in the elderly compared with younger persons. When elderly persons with IBD are cared for by a gastroenterologist, their outcomes tend to be better. However, as elderly persons with IBD continue to age, they may not have access to the same care as younger people with IBD due to deficiencies in their ability to use or access technology.

Proton Pump Inhibitor Use Before and After a Diagnosis of Inflammatory Bowel Disease.

BACKGROUND: Proton pump inhibitors (PPIs) have an impact on the gut microbiome. We investigated whether increased use of PPIs was associated with a diagnosis of inflammatory bowel disease (IBD). METHODS: The University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD between 1984 and 2018 with age-, sex-, and geography-matched control subjects and comprehensive prescription drug data from April 1995. Subjects were considered to be users if they received 2 PPI prescriptions. We assessed PPI prescriptions prediagnosis and for 3 years postdiagnosis of IBD. The absolute and relative rates were calculated and compared for PPI use pre- and post-IBD diagnosis. RESULTS: A total of 5920 subjects were diagnosed with IBD after April 1996. Rates of PPI use in control subjects increased gradually from 1.5% to 6.5% over 15 years. Persons with IBD had a higher rate of PPI use, peaking up to 17% within 1 year of IBD diagnosis with a rate ratio (RR) of 3.1 (95% confidence interval [CI], 2.9-3.3). Furthermore, persons with Crohn's disease (RR, 4.2; 95% CI, 3.7-4.6) were more likely to have been PPI users prediagnosis than persons with ulcerative colitis (RR, 2.4; 95% CI, 2.2-2.7). Important predictors of increased PPI use were older age, year of data collection, and Crohn's disease diagnosis. CONCLUSIONS: Persons with IBD have higher PPI use preceding their diagnosis. Possibly, the use of a PPI alters the gut microbiome, increasing the risk for IBD diagnosis; or persons with IBD have increased rates of dyspepsia, warranting PPI use; or some IBD symptoms are treated with PPIs whether warranted or not.

Proton pump inhibitor (PPI) use is increased in persons with IBD for up to years prior to their diagnosis, raising the possibility that their use increases the risk for inflammatory bowel disease (IBD), or alternatively, persons with IBD have more upper gastrointestinal complaints. Another possibility is that early IBD-related symptoms are being managed rightly or wrongly with PPI therapy. Further, there is an increased use of PPI therapy post­IBD diagnosis compared with matched control subjects. While the use of PPI therapy in persons with IBD may be appropriate, physicians need to rigorously review their use at all times, especially in persons with IBD, as in this population their use may be excessive and possibly detrimental.

Beyond Neutrophils for Predicting Relapse and Remission in Ulcerative Colitis.

BACKGROUND AND AIMS: This study examines colonic histological features in ulcerative colitis [UC] in endoscopic remission to determine which cell types and biopsy sites best predict a patient's likelihood of remaining in remission. METHODS: This is a retrospective chart, endoscopy and histology review of 166 patients with UC in endoscopic remission followed in a single inflammatory bowel disease practice over a median of 6 years [range, 2-11 years]. Clinical remission was based on global physician assessment and colonoscopy reports, and clinical relapse on chart review. Histological features of previous injury and also number and location of plasma cells and eosinophils were assessed. We evaluated all of these features semi-quantitatively using a standard set of illustrations for the grade to maintain consistency. Multiple logistic regression and survival analyses were used to identify features associated with relapse. RESULTS: Clinical relapse occurred in 44 patients. Ulceration, especially in the left colon, was highly predictive of relapse. In the absence of acute inflammation of ulceration, the variables most predictive of relapse were increased plasma cells in the basal 20% of the lamina propria, and eosinophils in the left colon. The variable most predictive of persistent remission was the presence of intra-epithelial eosinophils whether in the surface epithelium or within crypts, especially in the right colon. Lamina propria eosinophils [grade > 2] throughout the colon predicted relapse. CONCLUSION: In the absence of neutrophils or ulceration, left-sided plasmacytosis in the basal 20% of the lamina propria and increased lamina propria eosinophils provide the best indicators of relapse in UC in clinical and endoscopic remission.

Patient Experiences in the Management of Inflammatory Bowel Disease: A Qualitative Study.

Background: Inflammatory bowel disease (IBD) can lead to substantial impairments of quality-of-life. Clinical guidelines and quality indicators aid physicians in practice but may not reflect the perspectives and experiences of patients with IBD. To address this, the objectives of this study were to understand patient experiences with IBD care and to explore priorities. Methods: Based on a convenience sample of 36 participants, five focus groups were completed at four sites across Canada. Data were analyzed using a deductive thematic analysis approach to assess emergent themes and variability in participants' experiences. Results: Our results are organized by themes of structure, process and outcomes to illustrate common issues with respect to how care is organized in the healthcare system, how patients receive and experience care and how patients perceive the outcomes of their care. Our results frame a health systems quality approach that signal needed improvements in access to care, the need for innovation with respect to virtual medicine, the potential expansion of multidisciplinary team-based care and the importance of addressing the psychosocial dimensions for patients with IBD and their caregivers in order to better deliver patient-centred care. Conclusions: The issues identified have the potential to impact priority areas in the system, IBD care delivery, and how outcomes can be improved by focusing on 'lived experience' and patient-centred care. The differing values and perspectives of all those involved in caring for patients with IBD underscore the importance of good communication with patients, caregivers and family members, as well as staying responsive to evolving needs.

Controversies in Crohn's Disease Before and After Pouch Surgery.

BACKGROUND: IPAA is rarely performed in patients with a known diagnosis of Crohn's disease, although it may be done in highly selected patients with an absence of perianal disease or small bowel inflammation. Patients with a preoperative diagnosis of Crohn's disease are, however, at increased risk of developing Crohn's disease of the pouch. Crohn's disease of the pouch can also occur in people with a preoperative diagnosis of ulcerative colitis; however, it is unknown whether this phenotype is similar to classic Crohn's disease involving an intact bowel, or whether it is a distinct entity. OBJECTIVE: This study aimed to describe Crohn's disease of the pouch, including luminal inflammation, and fibrostenotic and perforating phenotypes, as well as management of these conditions. RESULTS: Crohn's disease of the pouch can present in similar ways as classic Crohn's disease, classified as either inflammatory, fibrostenotic, or penetrating. Criteria involving the diagnosis of Crohn's disease of the pouch are stringent to prevent unnecessary treatments, because a diagnosis of Crohn's disease after IPAA for presumed ulcerative colitis can cause mental anguish. Treatment of Crohn's disease of the pouch depends on the presenting phenotype, although therapies are similar to classic Crohn's disease. Endoscopic, or even surgical treatment, may be required for fibrostenotic and fistulizing diseases. LIMITATIONS: Crohn's disease of the pouch is a newly described disease of patients who undergo an ileoanal pouch anastomosis; and therefore, most of the evidence comes from retrospective trials in patients with an initial diagnosis of ulcerative colitis. CONCLUSIONS: While Crohn's disease of the pouch is controversial and perhaps a distinct disease within the spectrum of inflammatory bowel diseases, it nonetheless requires long-term medical therapy and close follow-up.

Effect of clinical versus administrative data definitions on the epidemiology of C. difficile among hospitalized individuals with IBD: a population-based cohort study.

BACKGROUND: Hospitalization admissions and discharge databases (DAD) using the International Classification of Diseases (ICD) codes are often used to describe the epidemiology of Clostridioides difficile infections (CDI) among those with Inflammatory bowel disease (IBD), even though DAD CDI definition can miss many cases of CDI. There are no data comparing the assessment of the epidemiology of CDI among those with IBD by DAD versus laboratory diagnosis. We used a population-based dataset to determine the effect of using DAD versus laboratory CDI diagnosis on CDI assessment among those with IBD. METHODS: We linked the University of Manitoba IBD Epidemiology Database to the provincial CDI laboratory dataset for the years 2005-2014. Time trends of CDI were assessed using joinpoint analyses. We used stratified logistic regression analysis to assess factors associated with CDI among individuals with IBD. RESULTS: Time trends of CDI among hospitalized individuals with IBD were similar when using DAD or the laboratory CDI diagnosis. Prior hospital admission and antibiotic exposure were associated with CDI using either of the CDI definitions, 5-ASA use was associated with CDI using DAD but not laboratory diagnosis, whereas corticosteroid exposure was associated with laboratory-based CDI diagnosis. Using laboratory results as gold standard, DAD had a sensitivity and specificity of 75.4% and 99.6% for CDI among those with IBD. CONCLUSIONS: Using ICD codes in the DAD for CDI provides similar epidemiological time trend patterns as identifying CDI in the laboratory dataset. Hence, ICD codes are reliable to determine CDI epidemiology among hospitalized individuals with IBD.

Achieving Histologic Normalization in Ulcerative Colitis Is Associated With a Reduced Risk of Subsequent Dysplasia.

BACKGROUND: Complete histologic normalization is associated with improved clinical outcomes in ulcerative colitis (UC). However, it is currently unknown what effect achieving histologic normalization has on the development of dysplasia. METHODS: We performed a retrospective analysis of 495 patients with a confirmed diagnosis of UC from a tertiary center. Patients were categorized according to the best histologic assessment they had during their disease course: histologic normalization, histologic quiescence, or persistent histologic activity. We assessed dysplasia rates in these patient groups after achieving histologic normalization or histologic quiescence, or 8 years after UC diagnosis in those with persistent histologic activity. Kaplan-Meier graphs and Cox regression analyses were performed to estimate this effect. RESULTS: The incidence rate of dysplasia development after achieving histologic normalization was statistically significantly less when compared with the incidence rate after achieving histologic quiescence (P = 0.001) and in those with persistent histologic activity 8 years after UC diagnosis (P = 0.033). In multivariate analysis, at any point throughout UC duration, dysplasia development was statistically lower in those with histologic normalization (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.13-0.81) but not in those with histologic quiescence (aHR, 0.52; 95% CI, 0.25-1.10), compared with those with persistent histologic inflammation. When assessing the time after achieving histologic normalization, histologic quiescence, or 8 years post UC diagnosis in those with persistent histologic activity, we found that patients with histologic normalization had a subsequent decreased risk of developing dysplasia (aHR, 0.09; 95% CI, 0.01-0.72), compared with patients without normalization. CONCLUSIONS: Histologic normalization is associated with a decreased risk in patients with UC of developing subsequent dysplasia, compared with patients without histologic normalization. These findings have implications for surveillance intervals.

Combining Cyclosporine With Ustekinumab in Acute Severe Ulcerative Colitis.

We have demonstrated the effectiveness and safety of combining cyclosporine and vedolizumab to treat ulcerative colitis (UC). We present 2 cases of hospitalized acute severe UC who had failed therapy with antitumor necrosis factor and vedolizumab and were treated successfully with induction cyclosporine and safely bridged to ustekinumab maintenance therapy. Both patients have avoided colectomy. There were no adverse events. We propose this novel treatment combination in medically resistant acute severe UC.

Real-World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis From 2 Tertiary IBD Centers in the United States.

Background: Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on real-world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from 2 US tertiary inflammatory bowel disease centers. Methods: Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Health (New York, New York) and University of Chicago Medical Center (Chicago, Illinois) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of ≤2, with a combined rectal bleeding and stool frequency subscore of ≤1. Results: Sixty-six UC patients were included. Ninety-two percent of patients had prior exposure to biologics or tofacitinib. Forty-three percent and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF nonresponse and endoscopic Mayo score of 3 were negative predictors of clinical remission. Thirty-three percent of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P < 0.01) and lower stool frequency (P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). Conclusions: In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials.

Cost-Effectiveness of 5-Aminosalicylate Therapy in Combination With Biologics or Tofacitinib in the Treatment of Ulcerative Colitis.

INTRODUCTION: Medications are major cost drivers in the treatment of patients with inflammatory bowel disease. Recent analyses suggest that there is no added efficacy in continuing nor harm in stopping 5-aminosalicylate (ASA) therapy in patients with inflammatory bowel disease escalated to biological therapies or tofacitinib. We assessed the cost-effectiveness of discontinuing 5-ASA therapy in patients with ulcerative colitis on biological therapies or tofacitinib, compared with continuing 5-ASA therapy. METHODS: We performed a cost-effectiveness analysis of 5-ASA with biologic therapy and tofacitinib compared with the same treatment without 5-ASA. Our primary outcome was to determine whether biologic/tofacitinib monotherapy was cost-effective compared with biologic/tofacitinib and 5-ASA combination therapy using the incremental cost-effectiveness ratio at a willingness to pay of $50,000/quality-adjusted life year. Owing to the uncertainty surrounding outcome probabilities, probabilistic sensitivity analyses with 10,000 simulations were also performed. We conducted a sensitivity analysis comparing biologic/tofacitinib and 5-ASA therapy compared with biologic/tofacitinib monotherapy, whereby vedolizumab was the first biologic used, followed by infliximab and finally tofacitinib. RESULTS: Our model shows that biologic/tofacitinib monotherapy dominates (cheaper and more effective) combination therapy of biologics/tofacitinib with 5-ASA. Probabilistic sensitivity analyses simulations resulted in biologic/tofacitinib monotherapy dominating 100% of the scenarios, with mean cost savings of $24,483.01 over 2 years. When vedolizumab was the first-line therapy in the sensitivity analysis, biologic/tofacitinib monotherapy continued to dominate the combination of 5-ASA and biologic/tofacitinib therapy. DISCUSSION: This analysis in patients with ulcerative colitis who require treatment with biologics or tofacitinib demonstrates that continuing 5-ASA therapy is not a cost-effective strategy. Discontinuation of 5-ASA therapy in these patients is safe and less expensive and should be recommended.

Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group. DISCUSSION: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.

Time trends and predictors of laboratory-confirmed recurrent and severe Clostridioides difficile infections in Manitoba: a population-based study.

BACKGROUND: Many previous studies of Clostridioides difficile infection (CDI) epidemiology have used hospital discharge data codes, which can have limited accuracy. We used a data set of laboratory-confirmed cases of CDI in the province of Manitoba, Canada, to describe the epidemiology of CDI over a decade. METHODS: We conducted a population-based historical cohort study using Manitoba Health's population-wide laboratory-based CDI data set linked to administrative health databases. All individuals living in Manitoba and experiencing a CDI episode between 2005 and 2015 were included (n = 8471) and followed up from CDI diagnosis. We assessed time trends of CDI, incidence and predictors of recurrence and severe outcomes, and health care encounters after CDI diagnosis. CDI episodes were stratified by community versus hospital site of acquiring CDI. RESULTS: Between 2005 and 2009, overall CDI diagnoses decreased by an average of 12.6% per year (95% confidence interval [CI] -4.4 to -20.0), with no statistically significant change from 2010 to 2015. In stratified analysis, incident and recurrent CDI had a similar decrease in the initial study time period and then stabilized. The proportion of community-associated CDI cases increased by an average of 4.8% per year (95% CI 2.8 to 6.8) during the study period. CDI acquired in a health care facility had a higher recurrence rate and more severe outcomes. Recurrence of CDI increased the likelihood of admission to hospital. INTERPRETATION: Between 2005 and 2015, the rates of overall laboratory-confirmed CDI, incident CDI, recurrent CDI and severe outcomes following CDI initially decreased before stabilizing, and an increasing proportion of CDI cases were community-associated. There is an increasing need to test for CDI among outpatients with diarrhea and to increase efforts to prevent recurrent CDI.

Cost-effectiveness analysis of a fecal microbiota transplant center for treating recurrent C.difficile infection.

OBJECTIVE: We assessed the cost-effectiveness of establishing a fecal microbial transplant (FMT) unit in Canada for the treatment of recurrent CDI. DESIGN: We performed a cost-effectiveness analysis to determine the number of patients with recurrent CDI needed to treat (NNT) annually to make establishing a FMT unit cost-effective. We compared treating patients for their second recurrence of CDI with FMT in a jurisdiction with a FMT unit, compared to being treated with antibiotics; then sent to a medical center with FMT available for the third recurrence. We used a willingness to pay threshold of $50,000 per quality-adjusted-life-year gained. RESULTS: The minimum annual NNT was 15 for FMT via colonoscopy, 17 for FMT via capsule, and 44 for FMT via enema compared with vancomycin, and 16, 18, and 47 compared with fidaxomicin, respectively. A medical center's minimum catchment area when establishing a FMT unit would have to be 56,849 if using FMT via colonoscopy, or 64,429 if using capsules. CONCLUSION: We report the minimum number of patients requiring treatment annually with FMT to achieve cost-effectiveness, when including start-up and ongoing costs. FMT is cost-effective in Canada in populations with a sufficient number of eligible patients, ranging from 15 to 47 depending on the FMT modality used. This is crucial for medical jurisdictions making decisions about establishing a FMT unit for the treatment of recurrent CDI. The cost-effectiveness can be generalized in other countries.