High-definition chromoendoscopy results in more significant dysplasia detection than white light endoscopy with random biopsies in ulcerative colitis patients: A single-center retrospective study.

The goal of this study was to determine whether high-definition white light endoscopy with random biopsies (HD-WLR) or chromoendoscopy (HDCE) yielded a higher dysplasia detection rate in ulcerative colitis patients. Ulcerative colitis (UC) patients have a 2.4-fold increased future risk of developing colorectal cancer compared to the general population and require careful dysplasia screening modalities. Both HD-WLR and HDCE are regularly used, and recent guidelines do not suggest a preference. UC patients who underwent dysplasia surveillance at our site between January 2019 and 2021 were retrospectively reviewed. We calculated the dysplasia detection rate of both techniques at the first CRC screening colonoscopy. Eighteen dysplastic lesions were detected in total, 3 by HD-WLR and fifteen by HDCE. Dysplasia was detected in 4% (3/75) and 20% (15/75) of UC patients by HD-WLR and HDCE respectively, with significantly fewer biopsies (4.44 ±â€…4.3 vs 29.1 ±â€…13.0) required using the former. HD-WLR detected 2 polypoid and one non-polypoid lesion, while HDCE detected eleven polypoid and 4 non-polypoid lesions. No invisible dysplasia or colorectal cancer was detected. Screening was performed at 10.8 ±â€…4.8 and 9.72 ±â€…3.05 years following UC diagnosis for HDCE and HD-WLR respectively. Median withdrawal time was 9.0 ±â€…2.7 minutes (HD-WLR) vs 9.6 + 3.9 minutes (HDCE). HDCE is associated with higher dysplasia detection rates compared to HD-WLR in a UC patient population. Given the former technique is less tedious and costly, our findings complement existing studies that suggest HDCE may be considered over HD-WLR for UC dysplasia surveillance.

Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program.

Objectives: The subjectivity of the Physician Global Assessment (PGA) is a limitation of the Mayo score in assessing severity of ulcerative colitis (UC). We compared treatment efficacy using endpoint definitions based on modified Mayo (mMayo) score, versus those based on Mayo score, using data from the tofacitinib OCTAVE program. Design: This post hoc analysis included data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain). Methods: Remission and clinical response [with nonresponder imputation (NRI)] were assessed using mMayo (without PGA) and Mayo scores, and further stratified by prior tumor necrosis factor inhibitor (TNFi) failure status. Results: At week 8 of OCTAVE Induction 1 and 2, remission rates with placebo and tofacitinib 10 mg twice daily (BID), respectively, were 7.7% and 24.8% (mMayo) and 6.0% and 17.6% (Mayo). At week 52 of OCTAVE Sustain, remission rates with placebo, tofacitinib 5 and 10 mg BID, respectively, were 12.1%, 35.9%, and 42.1% (mMayo) and 11.1%, 34.3%, and 40.6% (Mayo). A statistically significant (p < 0.05) treatment effect of tofacitinib versus placebo was observed for remission and clinical response at all time points, regardless of scoring definition or prior TNFi failure status. Conclusions: A significant effect of tofacitinib versus placebo was demonstrated across efficacy endpoints using mMayo score, consistent with previously reported data using Mayo score. Treatment effect sizes were generally similar regardless of scoring definition. This observation may help contextualize tofacitinib therapy outcomes with those of new UC therapies and support the use of Mayo score-based endpoints in UC clinical trials. Trail registration: ClinicalTrials.gov identifiers: NCT01465763; NCT01458951; NCT01458574.

A Novel Decision Aid Improves Quality of Reproductive Decision-Making and Pregnancy Knowledge for Women with Inflammatory Bowel Disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) with poor IBD-specific reproductive knowledge experience more childlessness and fear of IBD medications in pregnancy. The Pregnancy in IBD Decision Aid (PIDA), developed by an international multidisciplinary team, offers personalized online decision support regarding pregnancy in IBD. AIMS: Assess the impact of PIDA on quality of reproductive decision-making and pregnancy-related knowledge among preconception (PC) and pregnant patients with IBD, and evaluate acceptability to patients and clinicians. METHODS: PC and pregnant patients with IBD aged 18-45 completed questionnaires pre- and post-PIDA to assess quality of decision-making (Decisional Conflict Scale (DCS); Decision Self-Efficacy Scale (DSES) and IBD-in-pregnancy knowledge (Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow)). Paired t test assessed for differences pre- and post-PIDA. Patients and clinicians completed acceptability surveys. RESULTS: DCS and DSES were completed by 74 patients (42 Crohn's disease, 32 ulcerative colitis); 41 PC and 33 pregnant. DCS improved significantly post-PIDA in PC patients regarding pregnancy planning (t(40) = 4.83, p < 0.0001, Cohen's dz = 0.75) and in pregnant patients regarding medication management (t(32) = 2.37, p = 0.0242, dz = 0.41). DSES for PC patients improved significantly post-PIDA (t(40) = -3.56, p = 0.001, dz = -0.56). CCPKnow improved significantly post-PIDA in PC (t(42) = 4.93, p < 0.0001, dz = -0.75) and pregnant patients (t(32) = 5.1, p < 0.0001, dz = -0.89). PIDA was deemed optimal for length, readability, and content amount and considered highly useful by patients (n = 73) and clinicians (n = 14). CONCLUSIONS: Patients using PIDA developed an improved quality of reproductive decision-making and IBD-in-pregnancy knowledge. PIDA is an accessible tool that can empower women with IBD to make values-congruent, evidence-based decisions regarding pregnancy and may reduce voluntary childlessness.

Shared decision making in pregnancy in inflammatory bowel disease: design of a patient orientated decision aid.

BACKGROUND: Research has indicated a lack of disease-specific reproductive knowledge among patients with Inflammatory Bowel Disease (IBD) and this has been associated with increased "voluntary childlessness". Furthermore, a lack of knowledge may contribute to inappropriate medication changes during or after pregnancy. Decision aids have been shown to support decision making in pregnancy as well as in multiple other chronic diseases. A published decision aid for pregnancy in IBD has not been identified, despite the benefit of pre-conception counselling and patient desire for a decision support tool. This study aimed to develop and test the feasibility of a decision aid encompassing reproductive decisions in the setting of IBD. METHODS: The International Patient Decision Aid Standards were implemented in the development of the Pregnancy in IBD Decision Aid (PIDA). A multi-disciplinary steering committee was formed. Patient and clinician focus groups were conducted to explore themes of importance in the reproductive decision-making processes in IBD. A PIDA prototype was designed; patient interviews were conducted to obtain further insight into patient perspectives and to test the prototype for feasibility. RESULTS: Issues considered of importance to patients and clinicians encountering decisions regarding pregnancy in the setting of IBD included fertility, conception timing, inheritance, medications, infant health, impact of surgery, contraception, nutrition and breastfeeding. Emphasis was placed on the provision of preconception counselling early in the disease course. Decisions relating to conception and medications were chosen as the current focus of PIDA, however content inclusion was broad to support use across preconception, pregnancy and post-partum phases. Favourable and constructive user feedback was received. CONCLUSIONS: The novel development of a decision aid for use in pregnancy and IBD was supported by initial user testing.

Management of Biological Therapy Before Elective Inflammatory Bowel Disease Surgeries.

Increasing uptake of biologic therapy has contributed to declining surgical rates for inflammatory bowel disease (IBD). However, a significant number of patients on biologic therapy will go on to require surgery. The literature is conflicted with regard to the preoperative management of biologic therapy before urgent or elective IBD surgery. This article reviews the available data on postoperative complications following preoperative treatment with anti-tumor necrosis factor alpha therapy, anti-integrin therapy, and anti-interleukin therapy.

Pregnant Women with Inflammatory Bowel Disease Are at Increased Risk of Vitamin D Insufficiency: A Cross-Sectional Study.

BACKGROUND AND AIMS: Vitamin D insufficiency is prevalent in individuals with inflammatory bowel disease [IBD], as well as in pregnant women; however, the prevalence of vitamin D insufficiency in pregnant women with IBD is unknown. This study assessed the prevalence of vitamin D insufficiency in pregnant women with IBD and the adequacy of recommended supplementation. METHODS: A cross-sectional study was conducted in pregnant women with inflammatory bowel disease [Crohn's disease = 61, ulcerative colitis = 41] and without inflammatory bowel disease [n = 574]. Chi square tests and log binomial regression were used to examine the prevalence of vitamin D insufficiency. Covariates included ethnicity and season. Adequacy of vitamin D supplementation during pregnancy was also assessed. RESULTS: The prevalence of vitamin D insufficiency [25-OHD ≤75 nmol/L] in those with Crohn's disease was 50.8% (95% confidence interval [CI]: 38.4%-63.2%) and 60.9% [95% CI: 45.3%-74.7%] with ulcerative colitis compared with 17.4% [95% CI: 14.6%-20.8%] without inflammatory bowel disease. Women with inflammatory bowel disease were more likely to be vitamin D insufficient after adjusting for ethnicity and season (Crohn's disease-adjusted relative risk [aRR] = 2.98,;: 2.19-4.04; ulcerative colitis-aRR = 3.61; 95% CI: 2.65-4.93). Despite vitamin D supplementation, 32.3% [95% CI: 17.8%-51.2%] of those with Crohn's disease, 58.3% [95% CI: 37.1%-76.9%] of those with with ulcerative colitis, and 10.8% [95% CI: 6.9%-16.6%] of those without inflammatory bowel disease were still vitamin D insufficient. CONCLUSIONS: Pregnant women with inflammatory bowel disease are at increased risk of vitamin D insufficiency compared with those without inflammatory bowel disease. The current guidelines for vitamin D supplementation may be inadequate for pregnant women with inflammatory bowel disease.

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

OBJECTIVES: Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. METHODS: A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. RESULTS: A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). CONCLUSIONS: In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

Clinical Predictors of the Risk of Early Colectomy in Ulcerative Colitis: A Population-based Study.

BACKGROUND: A subset of patients with ulcerative colitis (UC) will require colectomy within a few years of diagnosis. Thus, our aim was to determine the clinical predictors of early colectomy among patients with UC who are hospitalized with an acute flare. METHODS: Using population-based surveillance (1996-2009), all adults (≥18 years) hospitalized for UC within 3 years of diagnosis (n = 489) were identified. The primary outcome was a colectomy within 3 years of diagnosis. All medical charts were reviewed. A logistic regression model evaluated clinical variables that predicted colectomy within 3 years of diagnosis, and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. RESULTS: Among patients admitted to hospital with UC within 3 years of diagnosis, 57.7% underwent colectomy, with the odds of colectomy decreasing by 12% per year. Early colectomy was more likely among patients aged 35 to 64 years versus 18 to 34 years (OR 2.18 [95% CI, 1.27-3.74]), males (OR 2.03 [95% CI, 1.24-3.34]), those with pancolitis (OR 5.38 [95% CI, 3.20-9.06]), and living in rural areas (OR 2.81 [95% CI, 1.49-5.29]). Prescription of infliximab before hospitalization increased odds of surgery (OR 5.12 [95% CI, 1.36-19.30]). CONCLUSIONS: Patients hospitalized for UC have a high risk of early colectomy. This is particularly true in middle-aged men, those living in rural areas, and those without response to infliximab.

Long-term Maintenance of Clinical, Endoscopic, and Radiographic Response to Ustekinumab in Moderate-to-Severe Crohn's Disease: Real-world Experience from a Multicenter Cohort Study.

BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. While effective in clinical trials for Crohn's disease (CD), long-term maintenance of response in the real-world setting is unclear. We aim to assess the efficacy of ustekinumab for maintaining clinical, endoscopic, and radiographic response in CD. METHODS: A retrospective multicenter cohort study was performed on patients with CD achieving steroid-free clinical response to ustekinumab induction, and advanced onto a regularly scheduled maintenance ustekinumab regimen between 2011 and 2016. The primary outcome was loss of response, defined by an increase in Harvey Bradshaw Index of >3 points from baseline requiring ustekinumab dose escalation, reinduction, rescue corticosteroids, immunomodulators, surgery, or ustekinumab discontinuation. Multivariate Cox proportional hazards regression was used to identify clinical factors associated with loss of response. RESULTS: One hundred four patients with CD achieving steroid-free response with ustekinumab induction were included; 92.3% (96/104) had previously failed antitumor necrosis factor therapy. Median follow-up was 57.2 weeks (interquartile range (IQR): 36.7-103.4). Cumulative probability of maintained response at 52 weeks was 71.8%. Sixty-seven patients (64.4%) maintained endoscopic or radiographic response. Thirty-five patients (33.7%) lost response at a median time of 47.4 weeks (IQR: 35.3-68.4). Dose escalation was required in 17 patients (16.3%); response was recaptured in 9/17 (52.9%). Nine patients (8.7%) required surgery. In Cox multivariate regression, concurrent immunomodulation was associated with reduced risk of loss of response (hazards ratio 0.39 (95% CI, 0.17-0.92)). CONCLUSIONS: Subcutaneous ustekinumab is an effective treatment option for maintaining long-term clinical, endoscopic, and radiographic response in patients with moderate-to-severe CD failing antitumor necrosis factor therapy.

Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy.

BACKGROUND & AIMS: It is unclear what are the best and most appropriate endoscopic procedures for detecting colonic neoplasia in patients with long-term colonic inflammatory bowel disease (IBD). Dye chromoendoscopy (DCE) is the standard used in IBD surveillance colonoscopies. However, studies are needed to determine the optimal endoscopic technique for detecting dysplastic lesions. We investigated current practices used in surveillance colonoscopies by IBD gastroenterologists at a single tertiary center. We also determined the rate of neoplasia detection among different surveillance endoscopic techniques in an analysis of random or targeted biopsies. METHODS: We collected data on 454 patients with IBD (54.5% male; mean age, 50 y; mean disease duration, 14.5 y; 55.9% with ulcerative colitis, 42.7% with Crohn's disease, and 1.3% with indeterminate colitis) who underwent surveillance colonoscopy from April 2011 through March 2014 at the University of Calgary in Canada. Subjects were examined using white-light standard-definition endoscopy (WLE), high-definition (HD) colonoscopy, virtual electronic chromoendoscopy (VCE), or DCE; random or targeted biopsy specimens were collected. Endoscopic and histologic descriptions with suspected neoplasia were recorded. Rates of neoplasia detection by the different endoscopic procedures were compared using chi-square analysis. RESULTS: Of the patients analyzed, 27.7% had WLE endoscopy with random collection of biopsy specimens, 27.3% had HD colonoscopy with random collection of biopsy specimens, 14.1% had VCE with random collection of biopsy specimens, 0.9% had DCE with random collection of biopsy specimens, 12.8% had HD colonoscopy with collection of targeted biopsy specimens, 11.9% had VCE with collection of targeted biopsy specimens, and 5.3% had DCE with collection of targeted biopsy specimens. Neoplastic lesions were detected in 8.2% of the procedures performed in the random biopsy group (95% confidence interval, 5.6-11.7) and 19.1% of procedures in the targeted biopsy group (95% confidence interval, 13.4-26.5) (P < .001). Neoplasias were detected in similar proportions of patients by HD colonoscopy, VCE, or DCE, with targeted biopsy collection. CONCLUSIONS: In a large cohort of IBD patients undergoing surveillance colonoscopy, targeted biopsies identified greater proportions of subjects with neoplasia than random biopsies. Targeted collection of biopsy specimens appears to be sufficient for detecting colonic neoplasia in patients undergoing HD colonoscopy, DCE, or VCE, but not WLE.

The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy.

BACKGROUND & AIMS: The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered. METHODS: A systematic literature search identified studies on the management of IBD during pregnancy. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. RESULTS: Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti-tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn's disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy. CONCLUSIONS: Optimal management of IBD before and during pregnancy is essential to achieving favorable maternal and neonatal outcomes.

Ulcerative colitis-associated hospitalization costs: a population-based study.

BACKGROUND: Hospitalization costs for ulcerative colitis (UC) following the introduction of infliximab have not been evaluated. OBJECTIVE: To study predictors of costs for UC patients who were hospitalized for a flare or colectomy. METHODS: Population-based surveillance identified adults (≥18 years of age) admitted to hospital for UC flare or colectomy between 2001 and 2009 in the Calgary Health Zone (Alberta). Medical charts were reviewed and patients stratified into three admission types: responsive to inpatient medical therapy (n=307); emergent colectomy (n=227); and elective colectomy (n=208). The annual median cost with interquartile range (IQR) was calculated. Linear regression determined the effect of admission type on hospital charges after adjusting for age, sex, smoking, comorbidities, disease extent, medication use (eg, infliximab) and year. The adjusted cost increase was presented as the percent increase with 95% CIs. Joinpoint analysis assessed for an inflection point in hospital cost after the introduction of infliximab. RESULTS: Median hospitalization cost for UC flare, emergent colectomy and elective colectomy, respectively, were: $5,499 (IQR $3,374 to $8,904), $23,698 (IQR $17,981 to $32,385) and $14,316 (IQR $11,932 to $18,331). Adjusted hospitalization costs increased approximately 6.0% annually (95% CI 4.5% to 7.5%). Adjusted costs were higher for patients who underwent an elective colectomy (percent increase cost 179.8% [95% CI 151.6% to 211.1%]) or an emergent colectomy (percent increase cost 211.1% [95% CI 183.2% to 241.6%]) than medically responsive patients. Infliximab in hospital was an independent predictor of increased costs (percent increase cost 69.5% [95% CI 49.2% to 92.5%]). No inflection points were identified. CONCLUSION: Hospitalization costs for UC increased due to colectomy and infliximab.

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

BACKGROUND & AIMS: There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. METHODS: We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. RESULTS: In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). CONCLUSIONS: Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries.

Intrapartum corticosteroid use significantly increases the risk of gestational diabetes in women with inflammatory bowel disease.

BACKGROUND AND AIMS: Women with inflammatory bowel disease (IBD) may be at higher risk of adverse pregnancy outcomes. This study compared perinatal outcomes in women with and without IBD. METHODS: The population-based Data Integration, Measurement, and Reporting (DIMR) administrative discharge database was used to identify women (≥18 years of age) in Alberta, Canada, with IBD who delivered a baby between 2006 and 2009 inclusive. Women without IBD were randomly sampled and matched in a 3:1 ratio to IBD cases by age at conception (±1 year). Odds ratios of gestational diabetes, preterm birth, low birth weight, cesarean section, and neonatal intensive care unit admission were calculated. RESULTS: One hundred and sixteen IBD patients were age-matched to 381 pregnant women without IBD. Gestational diabetes, preterm birth, and cesarean section were more common in women with IBD compared with controls (6.9 versus 1.8%, p = 0.03; 12.9 versus 0.3%, p < 0.0001; 43.1 versus 21.0%, p = 0.009, respectively). On multivariate analysis, women with IBD were independently more likely to have gestational diabetes (odds ratio [OR] = 4.3; 95% confidence interval [CI] 1.2-16.3), preterm birth (OR = 19.7, 95% CI 2.2-173.9), and to deliver by cesarean section (OR = 2.7, 95% CI 1.6-4.6) after adjusting for age and smoking status. CONCLUSION: Intrapartum corticosteroid use significantly increases the risk of gestational diabetes in women with IBD. Furthermore, IBD patients are at higher risk of preterm delivery and are more likely to undergo cesarean section compared with a healthy age-matched population. The finding of a higher risk of gestational diabetes is a novel finding not previously reported in the IBD literature.

Colectomy is a risk factor for venous thromboembolism in ulcerative colitis.

AIM: To compare venous thromboembolism (VTE) in hospitalized ulcerative colitis (UC) patients who respond to medical management to patients requiring colectomy. METHODS: Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by: (1) responsive to inpatient medical therapy (n=382); (2) medically refractory requiring emergent colectomy (n=309); and (3) elective colectomy (n=329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course (i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications (i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios (OR) with 95%CI. RESULTS: The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparin prophylaxis. In contrast, VTE was higher among patients who underwent an emergent (8.7%) and elective (4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal (45.8%) followed by lower extremity (19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective (adjusted OR=3.69; 95%CI: 1.30-10.44) and emergent colectomy (adjusted OR=5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time (adjusted OR=1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE. CONCLUSION: VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.

Funding a smoking cessation program for Crohn's disease: an economic evaluation.

OBJECTIVES: Patients with Crohn's disease (CD) who smoke are at a higher risk of flaring and requiring surgery. Cost-effectiveness studies of funding smoking cessation programs are lacking. Thus, we performed a cost-utility analysis of funding smoking cessation programs for CD. METHODS: A cost-utility analysis was performed comparing five smoking cessation strategies: No Program, Counseling, Nicotine Replacement Therapy (NRT), NRT+Counseling, and Varenicline. The time horizon for the Markov model was 5 years. The health states included medical remission (azathioprine or antitumor necrosis factor (anti-TNF), dose escalation of an anti-TNF, second anti-TNF, surgery, and death. Probabilities were taken from peer-reviewed literature, and costs (CAN$) for surgery, medications, and smoking cessation programs were estimated locally. The primary outcome was the cost per quality-adjusted life year (QALY) gained associated with each smoking cessation strategy. Threshold, three-way sensitivity, probabilistic sensitivity analysis (PSA), and budget impact analysis (BIA) were carried out. RESULTS: All strategies dominated No Program. Strategies from most to least cost effective were as follows: Varenicline (cost: $55,614, QALY: 3.70), NRT+Counseling (cost: $58,878, QALY: 3.69), NRT (cost: $59,540, QALY: 3.69), Counseling (cost: $61,029, QALY: 3.68), and No Program (cost: $63,601, QALY: 3.67). Three-way sensitivity analysis demonstrated that No Program was only more cost effective when every strategy's cost exceeded approximately 10 times their estimated costs. The PSA showed that No Program was the most cost-effective <1% of the time. The BIA showed that any strategy saved the health-care system money over No Program. CONCLUSIONS: Health-care systems should consider funding smoking cessation programs for CD, as they improve health outcomes and reduce costs.

Management of the pregnant inflammatory bowel disease patient on anti-tumour necrosis factor: state of the art and future directions.

Antitumour necrosis factor (anti-TNF) therapy has been a major advance in the treatment of inflammatory bowel disease (IBD) by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta), recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.

Update on ustekinumab for the treatment of Crohn's disease.

Despite the success of antitumor necrosis factor (TNF) therapy in Crohn's disease, there remains a need for biologic therapy that targets other immune pathways of disease. Ustekinumab is a fully human monoclonal immunoglobulin antibody that targets the interleukin (IL)-12 and IL-23 shared P40 subunit. It has been studied in 2 phase 2 randomized, double-blind, placebo-controlled trials in Crohn's disease. This article reviews the clinical efficacy and safety data of ustekinumab in Crohn's disease in anticipation of the final results of the phase III development program in moderate to severe Crohn's disease.

Assessment of variables associated with smoking cessation in Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) who smoke have a more complicated disease course. AIMS: Our primary objective was to assess smoking related variables that were associated with smoking cessation versus continued smoking in patients with CD. METHODS: A multi-center study identified CD patients who were seen at the University of Chicago and University of Calgary IBD clinics. Patients were categorized into three subgroups: lifetime non-smokers, current smokers, or ex-smokers. Participants completed questionnaires assessing their cigarette smoking behavior. Current smokers were prospectively followed for 6 months to assess smoking status and attempts to quit. Logistic regression analysis was performed to identify factors associated with smoking cessation. RESULTS: Three hundred patients were enrolled with 148 identifying themselves as lifetime non-smokers, 70 as current smokers, and 82 as ex-smokers. Patients who reported their first cigarette within 5 min of waking were more likely to be current smokers (OR = 21; 95% CI 3.94-107.3) as compared to patients who waited greater than 60 min. Current smokers were more likely to have one or more household members who smoked compared to ex-smokers (P < 0.05). Nearly half (49%) of the current smokers were in the precontemplation stage of change (i.e. no intention to quit smoking). At the 6-month follow-up, only 11% reported they quit smoking. CONCLUSIONS: Patients who report a short time to first cigarette in the morning may have more difficulty in smoking cessation. Current smokers were more likely to have another smoker in the household compared to ex-smokers. Current smokers had low levels of motivation to quit smoking and consequently with no intervention, very few quit 6 months after the baseline assessment.

Inflammatory bowel disease patients who leave hospital against medical advice: predictors and temporal trends.

BACKGROUND: Leaving hospital against medical advice (AMA) may have consequences with respect to health-related outcomes; however, inflammatory bowel disease (IBD) patients have been inadequately studied. Thus, we determined the prevalence of self-discharge, assessed predictors of AMA status, and evaluated time trends. METHODS: We analyzed the 1995-2005 Nationwide Inpatient Sample (NIS) to identify 93,678 discharges with a primary diagnosis of IBD admitted to the hospital emergently and did not undergo surgery. We described the proportion of IBD patients who left AMA. Predictors of AMA status were evaluated using a multivariate logistic regression model and temporal trend analyses were performed with Poisson regression models. RESULTS: Between 1995 and 2005, 1.31% of IBD patients left hospitals AMA. Crohn's disease (CD) patients were more likely to leave AMA (adjusted odds ratio [aOR], 1.53; 95% confidence intervals [CI]: 1.30-1.79). Characteristics associated with leaving AMA included: ages 18-34 (aOR, 7.77, 95% CI: 4.34-13.89); male (aOR, 1.75; 95% CI: 1.55-1.99); Medicaid (aOR, 4.55; 95% CI: 3.81-5.43) compared to private insurance; African Americans (aOR, 1.34; 95% CI: 1.09-1.64) compared to white; substance abuse (aOR, 2.75; 95% CI: 2.14-3.54); and psychosis (aOR, 1.55; 95% CI: 1.13-2.14). The incidence rates of self-discharge for CD patients were stable (P > 0.05) between 1995 and 1999, while they significantly (P < 0.0001) increased after 1999. In contrast, AMA rates for UC patients remained stable during the study period. CONCLUSIONS: Approximately 1 in 76 IBD patients admitted emergently for medical management leave the hospital AMA. These were primarily disenfranchised patients who may lack adequate outpatient follow-up.