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Background Primary cutaneous B-cell lymphoma (PCBCL) presents only in the skin at the time of diagnosis with no evidence of extracutaneous disease, and primary cutaneous follicle center lymphoma (PCFCL) is the most common subtype. There is currently a lack of prospective randomized control trials and large retrospective studies investigating the efficacy of different treatment options for PCFCL. This retrospective study was conducted to describe our local clinical experience and outcomes of patients treated with rituximab-containing regimens. Objectives To describe our local clinical experience and treatment outcomes of patients treated with rituximab-containing regimens. Methods A retrospective study consisting of 25 PCFCL patients treated with different modalities. Patient records were reviewed and analyzed using a Kaplan-Meier estimation and SAS 9.4 software. Results After the initial treatment, all patients had CR except for 1 patient in the observation group. Further, 60% of patients in surgery, 20% in chemoimmunotherapy, 67% in rituximab monotherapy, 33% in steroid injection/systemic prednisone, and 33% in observation experienced a relapse. Although no significant difference was found between treatment groups due to the small sample size, time to relapse trends provides insight into treatment responses. Chemoimmunotherapy had the lowest relapse rate in the first 5 years post-treatment, whereas surgery had a higher tendency to relapse. Conclusions Despite the potential for rituximab-containing chemoimmunotherapy to yield adverse effects, it is effective in achieving a prolonged clinical remission in patients with PCFCL. It remains a reasonable treatment option for diffuse, extensive, or treatment-resistant disease.

We investigated sleep disturbances, bowel movement (BM) kinetics, and travel experience with different bowel preparation regimens in a substudy of patients enrolled in a randomized multicenter Canadian clinical trial.Patients scheduled to have a colonoscopy between 7:30 am and 10:30 am (early morning) were randomized to (i) 4-L single-dose polyethylene glycol (PEG) given in the evening before, (ii) 2-L split-dose PEG (+bisacodyl 15 mg), or (iii) 4-L split-dose PEG. Patients scheduled to undergo a colonoscopy between 10:30 am and 4:30 pm (afternoon) were randomized to (iv) 2-L single-dose PEG (+bisacodyl 15 mg) in the morning, (v) 2-L split-dose PEG (+bisacodyl 15 mg), or (vi) 4-L split-dose PEG. Patients were asked to record information on BM kinetics, sleep, and travel to the endoscopy unit. Continuous and categorical variables were compared between groups using a Kruskal-Wallis test or χ 2 test, respectively. Intention-to-treat analyses were performed.Overall, 641 patients were included in this substudy. Patients undergoing early morning colonoscopies reported the most awakenings in the night when assigned to 4-L single-dose day-before PEG and the highest reduction in sleep hours when assigned to 4-L split-dose PEG. There were no significant between-group differences in urgent BMs, fecal incontinence episodes, or travel interruptions. Overall, 17% of those traveling for more than an hour had to stop for a BM during travel, with no significant difference between groups.Day-before and split-dose high-volume PEG regimens for colonoscopies scheduled before 10:30 am lead to the greatest sleep disturbance.

Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD.Using health administrative data and validated algorithms, we identified all children (16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models.The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05).Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

Introduction Invasive medical procedures such as colonoscopies can cause psychological distress and anxiety. Mycolonoscopy.ca is a multilanguage website that provides online written and video information (individual items reported in prior publications to be highly rated by patients) regarding preparation and what to expect before, during, and after colonoscopy. Information about how to access the website is included with all colonoscopy appointment materials in Winnipeg, Manitoba. We evaluated the use of mycolonoscopy.ca among patients undergoing colonoscopy and examined the association between visitation to the website and patient outcomes. Methods A paper-based survey was distributed to patients attending their colonoscopy appointments between 11/2019 and 3/2020. Logistic regression analyses were performed to determine the factors associated with website visitation, procedural worry, and bowel preparation scores. Results Five hundred and ninety-three surveys were distributed, of which 506 were completed. 17.4% of participants had visited the website before their colonoscopy. Visitors to mycolonoscopy.ca were more likely to consume a split-dose bowel preparation (63.9%) compared with non-visitors (52.5%) (P = 0.006). 31.3% of website visitors were very/extremely worried about their colonoscopy compared with 17.9% of non-visitors. 76.6% of individuals agreed/strongly agreed that visiting the website helped them prepare for their colonoscopy and 69.7% who visited the website agreed/strongly agreed that it helped to reduce their stress/anxiety for the procedure. In multivariable analyses, visitation to website was associated with higher adequate bowel preparation (OR:10.55; 95% CI:1.35 to 82.4). Conclusion Use of an informative online platform such as mycolonoscopy.ca can help to improve patient education before colonoscopy, reduce worry surrounding the procedure, and improve bowel preparation.

BackgroundProton 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).MethodsThe 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.ResultsA 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.ConclusionsPersons 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.

Background and Aims Although venous thromboembolism [VTE] is a well-known complication of inflammatory bowel disease [IBD] in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD. Methods We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children Results The 5-year incidence of VTE among 3593 children with IBD was 31.2 [95% CI 23.7–41.0] per 10 000 person-years [PY] compared to 0.8 [95% CI 0.4–1.7] per 10 000 PY among 16 289 children without IBD [unadjusted IRR 38.84, 95% CI 16.59–90.83; adjusted HR 22.91, 95% CI 11.50–45.63]. VTE was less common in Crohn’s disease than ulcerative colitis [unadjusted IRR 0.47, 95% CI 0.27–0.83; adjusted HR 0.52, 95% CI 0.29–0.94]. The findings were similar for deep vein thrombosis and pulmonary embolism when comparing children with and without IBD. Conclusions The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature. Conference Presentation: An abstract based on the data included in this paper was presented at Canadian Digestive Diseases Week [Montréal, Canada] in March 2020.

Objective This study aimed to determine whether having a diagnosis of asthma or allergic rhinitis (AR) increased the risk of being diagnosed with inflammatory bowel disease (IBD) and whether there was increased incidence of these diseases after a diagnosis of IBD. Design This is a retrospective, historical cohort–based study. We used the administrative data of Manitoba Health and the population-based University of Manitoba IBD Epidemiology Database. We used numbers of prescriptions for drugs used to treat asthma and to treat AR to identify diagnoses of asthma and AR, respectively. We calculated relative risks (RRs) to assess incidence of IBD compared with matched controls after diagnoses of asthma and AR and hazard ratios to determine the incidence of asthma and AR after IBD diagnosis. Results Compared with controls, a diagnosis of asthma or AR preceding a diagnosis of IBD was increased in cases (RR, 1.62; 95% confidence interval [CI], 1.50-1.75; and RR, 2.10; 95% CI, 1.97-2.24) with a similar outcome by subtype of IBD (Crohn’s disease vs ulcerative colitis) and by sex. On sensitivity analysis, diagnoses of asthma or AR were comparable when considering at least 5, 10, 15 or 20 drug prescriptions. Persons with IBD were more likely to develop asthma or AR than controls after being diagnosed with IBD (hazard ratio for asthma, 1.31, 95% CI, 1.18-1.45; and hazard ratio for AR, 2.62, 95% CI, 2.45-2.80). Conclusions The association between asthma, AR, and IBD suggest the possibility that whatever triggers the onset of these atopic diseases may trigger the onset of IBD as well, and aeroallergens are plausible culprits.

INTRODUCTION Venous thromboembolism (VTE) is known to be increased in inflammatory bowel disease (IBD). We aimed to determine whether rates of VTE in IBD have reduced over the past 30 years. METHODS We used the population-based University of Manitoba IBD Epidemiology Database (1984-2018) to determine the incidence of VTE in IBD and the incidence rate ratio vs matched controls. In persons with IBD with and without VTE, we assessed for variables that were associated with an increased risk of VTE on multivariate logistic regression. RESULTS The incidence of VTE in the IBD cohort was 7.6% which was significantly greater than in controls (3.3%, P < 0.0001). The overall age-standardized incidence rate of VTE was 433 per 100,000 in IBD and 184 per 100,000 in controls. The incidence of VTE was higher in Crohn's disease (8.4%) than in ulcerative colitis (6.9%, P = 0.0028). The incidence rate ratio in IBD vs controls was 2.36 (95% confidence interval 2.16-2.58). The increased risk was similar in males and females and in Crohn's disease compared with ulcerative colitis. The incidence rate among persons with IBD from 1985 to 2018 decreased very slowly, with annual percent change of -0.7% (P = 0.0003). Hospital admission, high comorbidity, use of antibodies to tumor necrosis factor for less than 3 years up until the time of the VTE, and the combination of steroid and antibodies to tumor necrosis factor increased the risk of VTE. DISCUSSION Despite advancements in IBD management in the past 30 years, the rates of VTE have only been slowly decreasing and remain significantly increased compared with controls.

Objectives Perioperative chemotherapy (P-CT) or neoadjuvant chemoradiation (C-RT) followed by surgical resection is the standard of care for locally advanced esophageal cancer (LAEC). We present an institutional review and outcome of patients with LAEC treated with neoadjuvant C-RT or P-CT followed by surgery. Methods Patients were identified through the Manitoba Cancer Registry. Overall survival (OS), recurrence-free survival (RFS), and time to recurrence (TTR) were compared using proportion hazard regression analysis. Metabolic and pathologic response rates were compared by the Fisher exact test. Results Sixty-seven patients were treated with C-RT and 32 with P-CT. Fifty-two percent of the patients had pretreatment and posttreatment positron emission tomography scans before surgery. Ninety-five percent of the patients in C-RT and 91% in P-CT had a partial metabolic response or stable disease. Sixty-one percent of C-RT and 34% of P-CT patients had tumor regression grade (TRG) 0 to 1; 39% of C-RT and 66% of P-CT had TRG 2 to 3 (P=0.018). Median OS was 37 and 18 months for patients with TRG 0 to 1 and 2 to 3, respectively (P=0.013, hazard ratio [HR]=1.96). Three-year OS was 43% versus 37% (P=0.37, HR=1.30), RFS was 34% versus 26% (P=0.87, HR=0.96), and median TTR was 30 versus 13 months (P=0.07, HR=0.59) for C-RT and P-CT, respectively. Conclusions C-RT was associated with a higher degree of pathologically tumor regression. Patients with major tumor regression had a better outcome than those with minimal to poor response. There was a trend toward improved TTR with C-RT but no difference in OS or RFS.

Manitoba implemented the first Canadian provincial program of reflex screening through mismatch repair immunohistochemistry (MMR-IHC) for all colorectal cancers diagnosed at age 70 years or younger in December 2017. We evaluated compliance to universal reflex testing and for referrals to Genetics for individuals with MMR-deficient tumors.We searched the provincial pathology database with "adenocarcinoma" in the colorectal specimen pathology reports between March 2018 and December 2020. We cross-referenced with paper and electronic records in the Program of Genetics and Metabolism to determine whether patients with MMR-deficient tumors had been referred for Genetic assessment and what proportion of patients and first-degree relatives accepted an appointment and genetic testing. We performed logistic regression analysis to identify predictors of testing.We identified 3,146 colorectal adenocarcinoma specimens (biopsies and surgical resections) from 1,692 unique individuals (mean age 68.66 years, male 57%). Of those aged 70 years or younger (n = 936), 89.4% received MMR-IHC screening. Individual pathologists (categorized by the highest, average, and lowest screening rates) were the biggest predictors of MMR-IHC screening on multivariable analysis (highest vs lowest: odds ratio 17.5, 95% confidence interval 6.05-50.67). While only 53.4% (n = 31) of 58 screen-positive cases were referred by pathologists for genetic assessment, other clinicians referred an additional 22.4% (n = 13), resulting in 75.8% overall referral rate of screen-positive cases. Thirteen (1.4%) patients (1.1%, aged 70 years or younger) were confirmed to experience Lynch syndrome through germline testing, and 8 first-degree relatives (an average of 1.6 per patient) underwent cascade genetic testing.The first Canadian Lynch syndrome screening program has achieved high rates of reflex testing.

Background We compared risks of nonmelanoma skin cancers (NMSCs) and melanoma preceding and following a diagnosis of inflammatory bowel disease (IBD) and to evaluate the effect of thiopurines and anti-tumor necrosis factor α (anti-TNF-α) on skin cancer risk in IBD. Methods This was a retrospective, historical cohort study using the population-based University of Manitoba IBD Epidemiology Database (11 228 IBD cases and 104 725 matched controls) linked to the Manitoba Cancer Registry. Logistic and Cox regression analyses were performed to calculate skin cancer risks prior to and after IBD diagnosis. Results Persons with ulcerative colitis (UC) were more likely to have basal cell carcinoma (BCC) predating their UC diagnosis (odds ratio, 1.32; 95% confidence interval [CI], 1.08-1.60). Risks of squamous cell carcinoma (SCC), other NMSCs, or melanoma prior to IBD diagnosis were not significantly increased. Post-IBD diagnosis, risks of BCC (hazard ratio, 1.53; 95% CI, 1.37-1.70) and SCC (hazard ratio, 1.61; 95% CI, 1.29-2.01) were significantly increased across all IBD groups except for SCC in UC. There was no significant association between melanoma and IBD post–IBD diagnosis. The risks of BCC and melanoma were increased in thiopurine and anti-TNF users, and risk of SCC was increased in only thiopurine users. Nested cohort analysis of persons with IBD with censoring at both thiopurines and anti-TNF use confirmed a higher baseline risk of BCC and no effect on SCC, comparable to pre-IBD diagnosis findings. Conclusions The risk of BCC preceding a diagnosis of UC is higher than in non-UC controls, compared with a generally increased risk of all NMSCs post–IBD diagnosis. Thiopurine and anti-TNF therapy increase the risks for skin cancers in persons with IBD after their diagnoses.

Metabolic and epigenetic reprogramming play important roles in cancer therapeutic resistance. However, their interplays are poorly understood. We report here that elevated TIGAR (TP53-induced glycolysis and apoptosis regulator), an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2 (nuclear receptor binding SET domain protein 2), is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 mark. Mechanistically, TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2, H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new (NSD2) and established (NQO1/2, PRDX1 and GSTM4) targets of NRF2, independent of its enzymatic activity. Nuclear TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy in vitro and in tumors through effective maintenance of redox homeostasis. In addition, nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor survival. These findings define a nuclear TIGAR-mediated epigenetic autoregulatory loop in redox rebalance for tumor therapeutic resistance.

Background Inflammatory bowel disease (IBD) is emerging in the developing world but phenotypic data are limited. We aimed to describe the phenotype, clinical presentation, disease behavior, and treatments of IBD in a large cohort in India. Methods All persons presenting to the Asian Institute of Gastroenterology in Hyderabad, India since 2004 with a confirmed diagnosis of IBD were enrolled. The demographic profile at the first visit, family history of IBD, smoking history, time from first symptom onset to diagnosis, use of anti-tuberculousis treatment before IBD-specific treatment, disease phenotype, and medication history were collected by interview and chart review. Disease and family history and treatments used were updated at each follow-up visit. Results Of 4006 persons enrolled, 59.9% had ulcerative colitis (UC) and the majority were male (60.3%). The median diagnostic delay in both UC and Crohn's disease (CD) was at least 2 years. At the time of diagnosis only 4.5% of CD were smokers and only 3.8% of UC were ex-smokers. Positive family history was uncommon (2.1%). The phenotype of persons with CD included 22.9% with stricturing disease and 9.4% with fistulizing disease. The most common site of disease was ileocolonic (40.9%) and only 2.5% had perineal fistulas. Among those with UC 18.7% had proctitis and 30.3% had pancolitis. Conclusions This is the largest cohort of persons with IBD reported from Asia. Although there are several demographic differences between persons with IBD from India compared with the West, the phenotypes of the disease are not highly different.

The timing of initiating biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations.We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups.Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery.Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC.

Metabolic and epigenetic reprogramming play important roles in cancer therapeutic resistance. However, their interplays are poorly understood. We report here that elevated TIGAR (TP53-induced glycolysis and apoptosis regulator), an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2 (nuclear receptor binding SET domain protein 2), is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 mark. Mechanistically, TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2, H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new (NSD2) and established (

Introduction We aimed to determine both direct (medical) and indirect (lost wages) costs of IBD and the association between the degree of IBD-related disability and extent of IBD-related costs. Methods Persons age 18-65 from the population-based University of Manitoba IBD Research Registry completed a survey including the IBD Disability Index (IBDDI) and questions related to employment, missed work (absenteeism), and reduced productivity at work (presenteeism). Administrative health data including surgeries, hospitalizations, physician claims, and prescriptions were linked to the survey and assessed. To calculate annual wage loss, number of days of missed work was multiplied by the average wage in Manitoba for the given occupation per Statistics Canada. Costs were adjusted to 2016-17 Canadian dollars. Using descriptive and regression analysis, we explored the association between IBDDI and annual direct and indirect costs associated with IBD. Results Average annual medical costs rose from $1918 among those with IBDDI 0-4 to $9,993 among those with IBDDI 80-86. Average annual cost of lost work rose from $0 among those with IBDDI 0-4 to $30,101 among those with IBDDI 80-86. Using linear regression, each additional unit of IBDDI was associated with an increase of $77 in annual medical cost (95% CI, $52-102; P < .001) and an increase of $341 in annual cost of lost wages (95% CI, $288-395; P < .001). Conclusions Costs related to IBD are significantly associated with the degree of IBD-related disability. Among the approximate 30% of the IBD population with IBDDI scores ≥40, the indirect costs of absenteeism and presenteeism accounts for ~75% of the total IBD-related costs.

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p &lt, 0.01), however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p &lt, 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p &lt, 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.

Objective To describe the patterns of care when persons with inflammatory bowel disease (IBD) present to the Emergency Department (ED) and post-ED follow-up. Methods We linked the University of Manitoba IBD Epidemiology Database with the Emergency Department Information System of the Winnipeg Regional Health Authority from January 1, 2010 to December 31, 2012. We then generated a list of all ED attendances by persons with IBD at four of six hospitals within the City of Winnipeg (two academic and two community hospitals). The charts were reviewed by two investigators extracting data on testing, consulting and treatment undertaken in the ED as well as postdischarge follow-up. We focused on outcomes among those attending the ED but not admitted to hospital. Results Of 1275 IBD patients with a first visit to the ED, 523 (41%) were for IBD-specific complaints. Three hundred and twenty-seven (62.5%) were discharged from the ED without an in-hospital admission. Nearly 80% had an identified gastrointestinal (GI) specialist (either gastroenterologist or GI surgeon) involved in their care. A gastroenterologist was consulted in the ED 20% of the time. Follow-up post-ED with a gastroenterologist was only documented in 36%. For those who saw a gastroenterologist in the ED, there was more likely to be a change in medications and follow-up arranged with a gastroenterologist. ED consultation with a gastroenterologist was the only predictor of seeing a gastroenterologist in follow-up post-ED. Conclusions ED gastroenterology consultation is more likely to effect IBD management change. When discharged from the ED gastroenterology, follow-up should be arranged and documented.

In addition to its morbidities, inflammatory bowel disease (IBD) has a major financial burden on patients and healthcare systems. However, there is a paucity of evidence on IBD-attributable costs in children.To determine the trends of IBD-attributable direct costs over time using a population-based analysis.Data were extracted from Manitoba Health Provider Claims and other population registry datasets from 1995 to 2017. Children with IBD were matched by age, sex and location with children without IBD. IBD-attributable direct costs were calculated using utilization counts from the administrative data and cost estimates from different sources. Inpatient hospitalisation and outpatient procedure costs were estimated using the resource intensity weight (RIW) that is attached to each record in the data. Costs were expressed in Canadian dollars.We included 733 (428 with Crohn's disease) prevalent cases who were diagnosed with IBD before the age of 18 years and were followed for 2450 person-years. A matched control group of 6763 persons who were followed for 21 558 person-years was included. The median annual costs of physician services billed per patient increased from $381 (IQR 215-1064) in 1995 to $936 (IQR 579-1932) in 2017 (P 0.001). The annual medication costs per patient increased from a median of $270 in 1995 to $7944 in 2017 (P 0.0001). The median annual direct cost per patient was $1810 in 2004 as compared to $14 791 (P 0.0001) in 2017.Over two decades, there was a significant increase in the paediatric IBD-attributable direct costs mainly driven by medication costs.

A prospective pilot study was carried out on 34 CLL patients treated with ibrutinib, evaluating the effects on symptoms and physical function with changes in plasma exosomes (EXs), β2-microglobulin (β2M) and 26 plasma cytokines. The revised Edmonton Symptom Assessment Scale (ESAS-R) demonstrated moderate fatigue, shortness of breath and a sense of unwellness before treatment, which significantly improved within 2 weeks of starting ibrutinib. These changes were associated with a rapid improvement in sit-to-stand and 4 m walking speeds. The plasma levels of CCL11, IL-7, -8 and -10 dropped initially while the levels of TNF-α/-β, CCL3, CCL4, CCL17, and IL-16 continued to decline for 12 months. Despite the initial lymphocytosis, plasma β2M levels fell but no consistent change in plasma EXs occurred. Thus, ibrutinib can produce a rapid and sustained improvement in symptoms and physical function in CLL, associated with a decline in multiple plasma cytokines.

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.

Introduction Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear. Methods We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time. Results The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1-4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1-2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC. Discussion Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.

Background We aimed to determine the prevalence of adverse childhood experiences (ACEs) in persons with inflammatory bowel disease (IBD) and whether having ACEs was associated with health care utilization post-IBD diagnosis. Method Three hundred forty-five participants from the population-based Manitoba IBD Cohort Study self-reported ACEs (ie, physical abuse, sexual abuse, death of a very close friend or family member, severe illness or injury, upheaval between parents, and any other experience thought to significantly impacts one’s life or personality) at a median of 5.3 years following IBD diagnosis. Cohort study data were linked to administrative health databases that captured use of hospitals, physician visits, and prescription drugs; use was classified as IBD-related and non-IBD-related. Mean annual estimates of health care use were produced for the 60-month period following the ACE report. Generalized linear models (GLMs) with generalized estimating equations (GEEs) with and without covariate adjustment were fit to the data. Results The prevalence of at least 1 ACE was 74.2%. There was no statistically significant association between having experienced an ACE and health care use. However, unadjusted mean annual non-IBD-related general practitioner visits were significantly higher for participants exposed to physical and sexual abuse than those not exposed. Selected adjusted rates of IBD-related health care use were lower for participants who reported exposure to an upheaval between parents and high perceived trauma from ACEs. Conclusion The estimated prevalence of at least 1 self-reported ACE in persons with diagnosed IBD was high. Health care use among those who experienced ACEs may reflect the impacts of ACE on health care anxiety.

Background We aimed to determine the costs of emergency department (ED) attendance by persons with inflammatory bowel disease (IBD) not admitted to hospital from the ED. Methods This was a population-based administrative database study linking the University of Manitoba IBD Epidemiology Database with the Winnipeg Regional Health Authority (WRHA) ED Information Service database. We identified persons with IBD who presented to the ED and were not admitted between January 1, 2009 and March 31, 2012. We then applied costs in Canadian dollars for these visits including an average ED visit cost plus 26% for overhead (total = $508), an average estimated cost of laboratory investigations ($50), and costs for each of radiographic imaging, lower endoscopy and consultation with an internist/gastroenterologist or a surgeon. We tallied the costs of each unique ED presentation. We determined average costs for visits associated with specific consultations or investigations. Results One thousand six hundred and eighty-two persons with IBD (4,853 individual visits) attended the ED and did not get hospitalized. The average cost per ED visit by a person with IBD who did not get hospitalized was $650. This resulted in a total expenditure of $3,152,227 on these persons for their ED attendance or $969,916 per year. The visits with the highest mean costs were those associated with an abdominal computerized tomography scan ($979), those associated with surgical consultation ($1019), and those associated with an internist/gastroenterologist consultation ($942). Conclusion Better strategies for management of acute issues for persons with IBD that can reduce the use of an ED are needed and can be considerably cost saving.

Eric I Benchimol,1–5 M Ellen Kuenzig,1,2,5 Charles N Bernstein,6,7 Geoffrey C Nguyen,5,8 Astrid Guttmann,5,9 Jennifer L Jones,10 Beth K Potter,4 Laura E Targownik,6,7 Christina A Catley,5 Zoann J Nugent,6,11 Divine Tanyingoh,12,13 Nassim Mojaverian,5 Fox E Underwood,12,13 Shabnaz Siddiq,1,2 Anthony R Otley,14 Alain Bitton,15 Matthew W Carroll,16 Jennifer C deBruyn,17 Trevor JB Dummer,18 Wael El-Matary,19 Anne M Griffiths,9 Kevan Jacobson,20,21 Desmond Leddin,10 Lisa M Lix,22 David R Mack,1–3 Sanjay K Murthy,4,23 Juan Nicolás Peña-Sánchez,24 Harminder Singh,6,7 Gilaad G Kaplan12,13 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium 1Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 2Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 3Department of Pediatrics, University of Ottawa, Ottawa, Canada; 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 5ICES, Toronto, Canada; 6University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada; 7Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; 8Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Canada; 9Department of Paediatrics, University of Toronto, Toronto, Canada; 10Department of Medicine, Dalhousie University, Halifax, Canada; 11CancerCare Manitoba, Winnipeg, Canada; 12Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 13Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 14Department of Pediatrics, Dalhousie University, Halifax, Canada; 15Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; 16Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada; 17Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada; 18School of Population and Public Health, University of British Columbia, British Columbia, Canada; 19Department of Pediatrics, University of Manitoba, Winnipeg, Canada; 20Department of Pediatrics, The University of British Columbia, British Columbia, Canada; 21Child and Family Research Institute, The University of British Columbia, British Columbia, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada; 23The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada Background and aims: Canada’s large geographic area and low population density pose challenges in access to specialized health care for remote and rural residents. We compared health services use, surgical rate, and specialist gastroenterologist care in rural and urban inflammatory bowel disease (IBD) patients in Canada.Methods: We used validated algorithms that were applied to population-based health administrative data to identify all people living with the following three Canadian provinces: Alberta, Manitoba, and Ontario (ON). We compared rural residents with urban residents for time to diagnosis, hospitalizations, outpatient visits, emergency department (ED) use, surgical rate, and gastroenterologist care. Multivariable regression compared the outcomes in rural/urban patients, controlling for confounders. Provincial results were meta-analyzed using random-effects models to produce overall estimates.Results: A total of 36,656 urban and 5,223 rural residents with incident IBD were included. Outpatient physician visit rate was similar in rural and urban patients. IBD-specific and IBD-related hospitalization rates were higher in rural patients (incidence rate ratio [IRR] 1.17, 95% CI 1.02–1.34, and IRR 1.27, 95% CI 1.04–1.56, respectively). The rate of ED visits in ON were similarly elevated for rural patients (IRR 1.53, 95% CI 1.42–1.65, and IRR 1.33, 95% CI 1.25–1.40). There were no differences in surgical rates or prediagnosis lag time between rural and urban patients. Rural patients had fewer IBD-specific gastroenterologist visits (IRR 0.79, 95% CI 0.73–0.84) and a smaller proportion of their IBD-specific care was provided by gastroenterologists (28.3% vs 55.2%, P65years (33.0% vs 59.2%, P

Background and Aims We aimed to determine whether monitoring of duodenoscope cleaning by rapid adenosine triphosphate (ATP) combined with channel-purge storage could eliminate high-concern microorganisms. Methods In a simulated-use study, suction channels, as well as lever recesses, from 2 duodenoscopes models and the unsealed elevator guidewire (EGW) channel from 1 of these 2 duodenoscopes (the other model has a sealed EGW) were perfused with ATS2015 containing approximately 8 Log 10 colony-forming units (CFU)/mL of both Enterococcus faecalis and Escherichia coli . Pump-assisted cleaning was monitored by rapid ATP testing. Duodenoscopes exceeding 200 relative light units (RLUs) were recleaned. Clean duodenoscopes were processed through an automated endoscope reprocessor and then stored in a channel-purge storage cabinet for 1 to 3 days. Cultures of EGW channel and instrument channel combined with the lever recess (IC-LR) were taken after storage. The impacts of extended cleaning and alcohol flush were evaluated. Results E coli was reliably eliminated in IC-LR and EGW channels of 119 duodenoscope tests (59 with sealed EGW and 60 with nonsealed EGW). However, actionable levels of E faecalis and environmental bacteria persisted. Neither alcohol flush nor extended cleaning resulted in a reduction of actionable levels for these organisms. Identification of isolates indicated that residual organisms in duodenoscope channels were hardy Gram-positive bacteria (often spore formers) that likely originated from environmental sources. Conclusions These data indicate that high-concern Gram-negative bacteria but not E faecalis or environmental bacteria can be reliably eliminated by use of the manufacturer's instructions for reprocessing with ATP monitoring of cleaning and channel-purge storage conditions.

Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome. Using the MTB, we performed immunohistochemistry on lung cancer tissue to determine expression of the AR and Ki67. These were then correlated with patient outcome. Of the 136 cases, 55% were female and 55% were adenocarcinoma. AR expression was not independently associated with outcome. Ki67 was associated with a significantly higher hazard ratio for death and recurrence (HR 2.19, 95% CI 1.30-3.70; HR 1.92, 95% CI 1.07-3.46, respectively). AR expression modified the effect of Ki67 on outcome, such that when both were expressed, there was no association with recurrence or survival (HR 2.39, 95% CI 1.31-4.36 for AR- Ki67+ vs HR 1.54, 95% CI 0.44-5.37 for AR+ Ki67+). Ki67 was associated with poorer outcomes alone. AR status alone was not associated with outcome. Although the mechanism remains unclear, AR status seems to negate the association of a high Ki67 and poor outcome.

Background Background: In addition to its symptomatic burden, inflammatory bowel disease (IBD) has a major financial burden on patients and healthcare systems. However, there is a paucity of evidence on IBD-attributable costs in children. In a population-based analysis, we determined the trends of IBD-attributable direct costs over 22 years. Methods Data were extracted from Manitoba Health Provider Claims, and other population registry datasets from 1995 to 2017. Children with IBD were matched by age, sex, and location with children without IBD. IBD-attributable direct costs were calculated using utilization counts from the administrative data and cost estimates from different sources. Inpatient hospitalization and outpatient procedure costs were estimated using the resource intensity weight (RIW) that is attached to each record in the data. Costs were expressed in 2018 Canadian dollars. Results We included 733 (428 with Crohn’s disease) prevalent cases who were diagnosed with IBD before the age of 18 years and were followed for 2450 person-years. An age, sex and geography matched control group of 6763 persons without IBD who were followed for 21558 person-years was included. The median annual physician’s billing fees increased from $381 (IQR 215–1064) in 1995 to $936 (IQR 579–1932) in 2017 (p Conclusion Over 2 decades, there was a significant increase in the pediatric IBD-attributable direct costs mainly driven by medication costs mainly anti-TNF biologics.

OBJECTIVEBiofilm has been implicated in bacterial persistence and survival after endoscope reprocessing. In this study, we assessed the impact of different methods of reprocessing on organic residues and viable bacteria after repeated rounds of biofilm formation when each was followed by full reprocessing.METHODSATS-2015, an artificial test soil containing 5–8 Log10 colony-forming units (CFU) of Enterococcus faecalis and Pseudomonas aeruginosa, was used to form biofilm in polytetrafluroethylene channels overnight on 5 successive days. Each successive day, full pump-assisted cleaning using bristle brushes or pull-through devices in combination with enzymatic or nonenzymatic detergents followed by fully automated endoscope reprocessor disinfection using peracetic acid was performed. Residuals were visualized by scanning electron microscopy (SEM). Destructive testing was used to assess expected cutoffs for adenosine triphosphate (ATP; 2), and viable bacteria count (0 CFU).RESULTSProtein residuals were above 2 µg/cm2, but ATP residuals were CONCLUSIONSSurviving E. faecalis and P. aeruginosa were only detected when the non-enzymatic detergent was used, emphasizing the importance of the detergent used for endoscope channel reprocessing. Preventing biofilm formation is critical because not all current reprocessing methods can reliably eliminate viable bacteria within the biofilm matrix.Infect Control Hosp Epidemiol 2017;38:1284–1290