Epidemiology, linkage to care and natural history of women of childbearing age with chronic hepatitis B: A population-based study.

Pregnant women with chronic hepatitis B (CHB) are a priority population for hepatitis B care. Identification of HBV status prior to pregnancy would facilitate timely maternal interventions and perinatal care. In our study, we aimed to study the epidemiology of CHB among women of childbearing age (WoCBA, 18-49 years) in Alberta, Canada. We retrospectively analysed Alberta Analytics databases to study CHB epidemiology, natural history and care linkage among WoCBA in Alberta, between April 2012 and March 2021. A Poisson regression was conducted to estimate incidence of newly identified CHB cases and prevalence trends, whereas predictors of care linkage were determined using logistic regression. Age/sex-adjusted incidence of newly identified CHB among WoCBA between 2015 and 2020 was 36.2/100,000 person/years, highest among individuals aged 30-39 years. Incidence of newly identified CHB decreased from 52.6 to 18.2/100,000 between 2015 and 2020, but prevalence increased from 131.7 to 248.6/100,000 in the same period. Newly identified CHB incident cases (n = 2124) had lower survival rates than age/sex-matched Canadians, with a standardized mortality ratio of 5.7 (95% CI 2.6-11.0). Increasing age (years) at diagnosis (HR, 1.2; 95% CI 1.1-1.3) was independently associated with mortality. Comorbid hepatocellular carcinoma, anti-HBV treatment and year of diagnosis were not significantly associated with mortality. Of the 1927 women with 2436 hepatitis B surface antigen-positive pregnancies from 2012 to 2020, only 27.6% had recommended HBV assessment during pregnancy. Of those women meeting criteria for antiviral therapy to prevent mother-to-child transmission (MTCT), only 66.4% received treatment. Suboptimal management during pregnancy and overall lower survival rates highlight the need to address care linkage barriers in women of childbearing age living with CHB.

Immunological effects and safety of live rotavirus vaccination after antenatal exposure to immunomodulatory biologic agents: a prospective cohort study from the Canadian Immunization Research Network.

BACKGROUND: People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6-12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network. METHODS: In this prospective cohort study, infants exposed to biologic agents in utero were referred to one of six SIC sites in Canada for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or older than 15 weeks were excluded. Clinical and laboratory evaluations were conducted according to a standard clinical pathway. Data were collected for relevant medical history, pregnancy outcomes, biologic agent exposure history, physical examination, laboratory results of the child, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunisation. After parental consent, deidentified data were transferred to a central database for analysis. Children recommended for rotavirus vaccination were followed up for 8 months after series initiation to ascertain severe and serious adverse events, including severe diarrhoea, vomiting, and intussusception. FINDINGS: Between May 1, 2017, and Dec 31, 2021, 202 infants were assessed and 191 eligible infants were enrolled (97 [51%] were female and 94 [49%] were male). When including those exposed to multiple agents, the most common biologic agents to which infants were exposed were infliximab (67 [35%] of 191), adalimumab (49 [26%]), ustekinumab (18 [9%]), and vedolizumab (17 [9%]). Biologic agent exposure continued into the third trimester for 178 (93%) infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. After SIC assessment, rotavirus vaccination was recommended for 187 (98%) of 191 infants, all of whom were followed up. By end of follow-up on Aug 19, 2022, 168 (90%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious adverse events after immunisation were reported, but three (2%) infants required medical attention, one for vomiting and change in stools who was subsequently diagnosed with gastroesophageal reflux disease, one for rash on labia unrelated to vaccination, and one for vomiting and diarrhoea associated with a milk allergy. INTERPRETATION: Findings from this study suggest that lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination can be offered to infants exposed to anti-TNF agents in utero. FUNDING: Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network.

Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods: We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results: A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn's disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion: Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.

Inflammatory Bowel Disease Among Canadian Children: Comparison Between Children of Non-European Descent and Children of European Descent.

BACKGROUND: Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. METHODS: Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups. Prospectively collected data at diagnosis and follow-up were compared between ancestral groups. RESULTS: Among 1447 children (63.2% Crohn's disease, 30.7% ulcerative colitis), 67.8% were European, 9.4% were South Asian, 3.8% were West Central Asian and Middle Eastern, 2.3% were African, 2.2% were East/South East Asian, 2.0% were Caribbean/Latin/Central/South American, 9.9% were mixed, and 2.6% were other. Children of African descent with ulcerative colitis had an older age of diagnosis compared with children of European descent (median 15.6 years vs 13.3 years; P = .02). Children of European descent had a higher proportion of positive family history with IBD (19.3% vs 12.1%; P = .001) compared with children of non-European descent. Children of European descent also had a lower proportion of immigrants and children of immigrants compared with children of non-European descent (9.8% vs 35.9%; P < .0001; and 3.6% vs 27.2%; P < .0001, respectively) . CONCLUSIONS: Important differences exist between different ancestral groups in pediatric patients with IBD with regard to age of diagnosis, family history, and immigrant status. Our study adds to the knowledge of the impact of ancestry on IBD pathogenesis.

This study explores the ancestral and phenotypic variation of Canadian children newly diagnosed with inflammatory bowel disease. It identifies differences between children of European and non-European descent in phenotypes of inflammatory bowel disease, disease location and behavior, family history, and immigrant status.

Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

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

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

Observational data from the adalimumab post-marketing PYRAMID registry of patients with Crohn's disease who became pregnant: A post hoc analysis.

BACKGROUND: PYRAMID was an international post-marketing registry that aimed to collect data on the long-term safety and effectiveness of adalimumab treatment per local standard of care in patients with moderately to severely active Crohn's disease (CD). Here, we present post hoc analyses of observational data from patients who became pregnant while participating in this registry and receiving adalimumab. METHODS: From the subpopulation of patients receiving adalimumab who became pregnant while taking part in PYRAMID, data on patient characteristics, pregnancy outcomes, and complications of pregnancy were analysed retrospectively. RESULTS: Across the PYRAMID registry, 293 pregnancies occurred in patients who had gestational adalimumab exposure (average disease duration at last menstrual period: 8.6 years), resulting in 300 pregnancy outcomes. A total of 197 pregnancies (67.2%) were exposed to adalimumab in all trimesters per physician's decision. Of the known reported outcomes (96.3%), 81.7% (236/289) were live births, 10.4% (30/289) were spontaneous abortions, 4.8% (14/289) elective terminations, 2.8% (8/289) ectopic pregnancies, and 0.3% (1/289) was a stillbirth. Congenital malformations (pulmonary valve stenosis and tricuspid valve incompetence) were reported in one infant. In addition to the pregnancy outcomes described above, 23 complications of pregnancy were reported in 20 patients. CONCLUSIONS: This analysis showed that adalimumab treatment in patients with CD, who became pregnant whilst participating in the PYRAMID registry, contributed no additional adverse effects during the pregnancy course or on pregnancy outcomes.

Association between chronic conditions and urinary incontinence in females: a cross-sectional study using national survey data.

BACKGROUND: Urinary incontinence affects up to half of women, yet few speak to their health care provider about or receive treatment for the condition. To aid with identifying subpopulations at risk for urinary incontinence, we examined the associations between 10 chronic health conditions and urinary incontinence among Canadian adult females. METHODS: We conducted a cross-sectional analysis of survey data from the Canadian Community Health Survey (2013-2014) involving female respondents aged 25 years or older living in a private dwelling. Presence of chronic conditions and urinary incontinence were measured by self-report. We used logistic regression modelling with sampling weights, controlling for age, income, ethnicity, body mass index and smoking. Multiple imputation and probabilistic bias analysis were used to address missing covariate data and unmeasured confounding from parity. RESULTS: Our analysis included 60 186 respondents representing more than 12 million Canadian females, of whom 45.8% (95% confidence interval [CI] 45.0%-46.6%) reported at least 1 chronic condition. Chronic conditions were associated with more than twice the odds of urinary incontinence (adjusted odds ratio [OR] 2.42, 95% CI 2.02-2.89). Associations were largest for bowel disorders (adjusted OR 2.92, 95% CI 2.44-3.49); modest for chronic obstructive pulmonary disease (adjusted OR 2.00, 95% CI 1.63-2.45), asthma (adjusted OR 1.82, 95% CI 1.52-2.19), arthritis (adjusted OR 1.98, 95% CI 1.74-2.24) and heart disease (adjusted OR 1.73, 95% CI 1.48-2.02); and smallest for diabetes (adjusted OR 1.20, 95% CI 1.02-1.41) and high blood pressure (adjusted OR 1.27, 95% CI 1.12-1.44). Results slightly attenuated but did not substantively change after imputation and bias analysis. INTERPRETATION: We found that chronic conditions are associated with significantly higher odds of comorbid urinary incontinence among Canadian adult females, which is consistent with previous research. Our findings support routine inquiry regarding urinary incontinence symptoms among women accessing health care for chronic conditions.

Ustekinumab Therapeutic Drug Monitoring-Impact on Clinical Practice: A Multicenter Cross-Sectional Observational Trial.

BACKGROUND AND AIMS: The value of ustekinumab (UST) therapeutic drug monitoring (TDM) in clinical practice remains unclear. This study examined the impact of UST TDM on clinical decision making in patients with Crohn's disease (CD). METHODS: A total of 110 consecutive UST-treated CD patients were enrolled in this multicenter, single-arm cross-sectional study. During a single study visit, clinical decisions, disease characteristics, and serum and fecal samples were obtained. The primary outcome was congruency of the actual and two hypothetical clinical decisions based on provision of UST TDM (with and without fecal calprotectin [FCP]) to participating clinicians. Decisions were compared against those of a review panel. A sub-study retrospectively measured the associations of clinical outcomes at the next follow-up visit with serum UST concentration [UST]. RESULTS: No differences in the pattern of decisions by clinicians were observed before and after provision of UST TDM (P = 1.0) or UST TDM + FCP (P = 0.86). However, 39% (TDM) and 50% (TDM + FCP) of hypothetical decisions differed from the initial decisions. The review panel's decisions differed with the addition of TDM + FCP (P = 0.0006), but not TDM alone (P = 0.16). The sub-study (n = 53) failed to detect an association between therapeutic serum [UST] at the initial study visit and clinical outcomes at the next visit. CONCLUSIONS: In consecutive CD patients treated with UST, the addition of TDM into routine clinical practice did not significantly impact clinical decisions and there was no association between short-term clinical outcomes and serum [UST]. Further studies are warranted before clinicians routinely implement UST TDM into clinical practice.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Surgery for Inflammatory Bowel Disease Has Unclear Impact on Female Fertility: A Cochrane Collaboration Systematic Review.

BACKGROUND AND AIMS: Surgical treatment of inflammatory bowel disease (IBD) may impair female fertility. We conducted a systematic review to determine the risk of infertility and pregnancy outcomes in women with IBD who underwent surgery. METHODS: We identified studies evaluating the impact of IBD surgery on infertility and pregnancy outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were pooled when data were presented using contingency tables. Odds ratios (OR) were pooled when raw numbers were not provided. GRADE was used to evaluate the certainty of evidence. RESULTS: Sixteen observational studies were included, comparing women with and without surgery, open and laparoscopic surgery and before and after surgery. All studies were of low quality. The effect of surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57) was uncertain. Similarly, the fertility effects of laparoscopic versus open surgery method were unclear (RR 0.70, 95% CI 0.38 to 1.27). The impact of IBD surgery on pregnancy outcomes should be interpreted with caution. Surgery was associated with miscarriage (OR 2.03, 95% CI 1.14 to 3.60), use of assisted reproductive technologies (RR 25.09, 95% CI 1.56 to 403.76) and caesarean section (RR 2.23, 95% CI 1.00 to 4.95), but not with stillbirth (RR 1.96, 95% CI 0.42 to 9.18), preterm birth (RR 1.91, 95% CI 0.67 to 5.48), low birth weight (RR 0.61, 95% CI 0.08 to 4.83) or small for gestational age (RR 2.54, 95% CI 0.80 to 8.01). CONCLUSION: The effect of surgical therapy for IBD on rates of female infertility and pregnancy-related outcomes was uncertain due to poor quality of existing literature.

Smoking May Reduce the Effectiveness of Anti-TNF Therapies to Induce Clinical Response and Remission in Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Cigarette smoking worsens prognosis of Crohn's disease [CD]. We conducted a systematic review and meta-analysis to examine the association between smoking and induction of clinical response or remission with anti-tumour necrosis factor [TNF] therapy. METHODS: MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL [June 2019] were searched for studies reporting the effect of smoking on short-term clinical response and remission to anti-TNF therapy [≤16 weeks following the first treatment] in patients with CD. Risk ratios [RR] with 95% confidence intervals [CI] were calculated using random-effects models. RESULTS: Eighteen observational studies and three randomised controlled trials [RCT] were included. Current smokers and non-smokers [never or former] had similar rates of clinical response [observational studies RR: 0.96; 95% CI: 0.88, 1.05; RCTs RR: 1.09; 95% CI: 0.84, 1.41]. When restricted to studies clearly defining the smoking exposure, smokers treated with anti-TNF were less likely to achieve clinical response than non-smokers [smokers defined as having ≥5 cigarettes/day for ≥6 months RR: 0.63; 95% CI: 0.48, 0.83; lifetime never smokers vs ever smokers excluding former smokers RR: 0.81; 95% CI: 0.71, 0.93]. Current smokers were also less likely to achieve clinical remission in observational studies [RR: 0.75; 95% CI: 0.57, 0.98], though this association was not seen in RCTs [RR: 1.04; 95% CI: 0.89, 1.21]. CONCLUSIONS: Smoking is significantly associated with a reduction in the ability of infliximab or adalimumab to induce short-term clinical response and remission when pooling studies where smoking status was clearly defined. When patients with CD are treated with highly effective therapy, including anti-TNF agents, concurrent smoking cessation may improve clinical outcomes.

Patient preferences for maintenance therapy in Crohn's disease: A discrete-choice experiment.

OBJECTIVE: To quantify patient preferences for maintenance therapy of Crohn's disease and understand the impact on treatment selection. METHODS: We conducted a discrete-choice experiment in patients with Crohn's disease (n = 155) to measure the importance of attributes relevant to choosing between different medical therapies for maintenance of Crohn's disease. The attributes included efficacy and withdrawals due to adverse events, as well as dosing and other rare risks of treatment. From the discrete-choice experiment we estimated the part-worth (importance) of each attribute level, and explored preference heterogeneity through latent class analysis. We then used the part-worths to apply weights across each outcome from a prior network meta-analysis to estimate patients' preferred treatment in pairwise comparisons and for the overall group of treatments. RESULTS: The discrete-choice experiment revealed that maintaining remission was the most important attribute. Patients would accept a rare risk of infection or cancer for a 14% absolute increased chance of remission. Latent class analysis demonstrated that 45% of the cohort was risk averse, either to adverse events or requiring a course of prednisone. When these preferences were used in modelling studies to compare pairs of treatments, there was a ≥ 78% probability that all biologic treatments were preferred to azathioprine and methotrexate, based on the balance of benefits and harms. When comparing all treatments, adalimumab was preferred by 53% of patients, who were motivated by efficacy, and vedolizumab was preferred by 30% who were driven by the preference to avoid risks. However, amongst biologic treatment options, there was considerable uncertainty regarding the preferred treatment at the individual patient level. CONCLUSION: Patients with Crohn's disease from our population were, on average, focused on the benefits of treatment, supporting intensive treatment approaches aimed at maintaining remission. Important preference heterogeneity was identified, however, highlighting the importance of shared decision making when selecting treatments.

Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old, or Obstetric.

The epidemiology of inflammatory bowel disease (IBD) is progressively evolving impacting the type of patients with IBD we will see in clinical practice. In this review, we discuss specific challenges and solutions in the management of (1) obese, (2) older and (3) obstetric (pregnant) patients with IBD. With the global obesity epidemic, almost 1 in 3 patients with IBD are obese. Obesity is associated with greater difficulty in achieving remission, higher risk of disease relapse and higher burden and costs of hospitalization in patients with IBD. Obese patients also have inferior response to biologic therapy related to altered pharmacokinetics and obesity-mediated chronic inflammation. Surgical management of obese patients with IBD is also challenging. Similar to obesity, the prevalence of IBD in older patients is rising and it is anticipated that almost one-third of patients with IBD will be older than 60 years within the next decade. Older patients present unique diagnostic and therapeutic dilemmas, and management of these individuals warrants careful consideration of the risks of disease-related versus treatment-related complications, non-IBD-related extra-intestinal complications (eg, cardiovascular disease, malignancy), in the context of individual values, preferences, functional status and comorbidities. With evolving therapeutics, medical management of IBD surrounding pregnancy continues to be challenging. Overall, the management of pregnant patients requires a pro-active, multidisciplinary approach, with an emphasis on optimal disease control not just during, but prior to pregnancy. This often involves continuation of highly effective therapies, of which the vast majority are safe during pregnancy and breastfeeding, resulting in a reduction of risk of adverse maternal fetal outcomes.

Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease.

BACKGROUND & AIMS: Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. METHODS: We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. RESULTS: The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. CONCLUSIONS: Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

The impact of surgical therapies for inflammatory bowel disease on female fertility.

BACKGROUND: Women with inflammatory bowel disease (IBD) may require surgery, which may result in higher risk of infertility. Restorative proctocolectomy with ileal anal pouch anastomosis (IPAA) may increase infertility, but the degree to which IPAA affects infertility remains unclear, and the impact of other surgical interventions on infertility is unknown. OBJECTIVES: Primary objective• To determine the effects of surgical interventions for IBD on female infertility.Secondary objectives• To evaluate the impact of surgical interventions on the need for assisted reproductive technology (ART), time to pregnancy, miscarriage, stillbirth, prematurity, mode of delivery (spontaneous vaginal, instrumental vaginal, or Caesarean section), infant requirement for resuscitation and neonatal intensive care, low and very low birth weight, small for gestational age, antenatal and postpartum hemorrhage, retained placenta, postpartum depression, gestational diabetes, and gestational hypertension/preeclampsia. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to September 27, 2018, to identify relevant studies. We also searched references of relevant articles, conference abstracts, grey literature, and trials registers. SELECTION CRITERIA: We included observational studies that compared women of reproductive age (≥ 12 years of age) who underwent surgery to women with IBD who had a different type of surgery or no surgery (i.e. treated medically). We also included studies comparing women before and after surgery. Any type of IBD-related surgery was permitted. Infertility was defined as an inability to become pregnant following 12 months of unprotected intercourse. Infertility at 6, 18, and 24 months was included as a secondary outcome. We excluded studies that included women without IBD and those comparing women with IBD to women without IBD.. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and extracted data. We used the Newcastle-Ottawa Scale to assess bias and GRADE to assess the overall certainty of evidence. We calculated the pooled risk ratio (RR) and 95% confidence interval (CI) using random-effects models. When individual studies reported odds ratios (ORs) and did not provide raw numbers, we pooled ORs instead. MAIN RESULTS: We identified 16 observational studies for inclusion. Ten studies were included in meta-analyses, of which nine compared women with and without a previous IBD-related surgery and the other compared women with open and laparoscopic IPAA. Of the ten studies included in meta-analyses, four evaluated infertility, one evaluated ART, and seven reported on pregnancy-related outcomes. Seven studies in which women were compared before and after colectomy and/or IPAA were summarized qualitatively, of which five included a comparison of infertility, three included the use of ART, and three included other pregnancy-related outcomes. One study included a comparison of women with and without IPAA, as well as before and after IPAA, and was therefore included in both the meta-analysis and the qualitative summary. All studies were at high risk of bias for at least two domains.We are very uncertain of the effect of IBD surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57; 114 participants; 2 studies) and at 24 months (RR 3.59, 95% CI 1.32 to 9.73; 190 participants; 1 study). Infertility was lower in women who received laparoscopic surgery compared to open restorative proctocolectomy at 12 months (RR 0.70, 95% CI 0.38 to 1.27; 37 participants; 1 study).We are very uncertain of the effect of IBD surgery on pregnancy-related outcomes, including miscarriage (OR 2.03, 95% CI 1.14 to 3.60; 776 pregnancies; 5 studies), use of ART (RR 25.09, 95% CI 1.56 to 403.76; 106 participants; 1 study), delivery via Caesarean section (RR 2.23, 95% CI 1.00 to 4.95; 20 pregnancies; 1 study), stillbirth (RR 1.96, 95% CI 0.42 to 9.18; 246 pregnancies; 3 studies), preterm birth (RR 1.91, 95% CI 0.67 to 5.48; 194 pregnancies; 3 studies), low birth weight (RR 0.61, 95% CI 0.08 to 4.83), and small for gestational age (RR 2.54, 95% CI 0.80 to 8.01; 65 pregnancies; 1 study).Studies comparing infertility before and after IBD-related surgery reported numerically higher rates of infertility at six months (before: 1/5, 20.0%; after: 9/15, 60.0%; 1 study), at 12 months (before: 68/327, 20.8%; after: 239/377, 63.4%; 5 studies), and at 24 months (before: 14/89, 15.7%; after: 115/164, 70.1%; 2 studies); use of ART (before: 5.3% to 42.2%; after: 30.3% to 34.3%; proportions varied across studies due to differences in which women were identified as at risk of using ART); and delivery via Caesarean section (before: 8/73, 11.0%; after: 36/75, 48.0%; 2 studies). In addition, women had a longer time to conception after surgery (two to five months; 2 studies) than before surgery (5 to 16 months; 2 studies). The proportions of women experiencing miscarriage (before: 19/123, 15.4%; after: 21/134, 15.7%; 3 studies) and stillbirth (before: 2/38, 5.3%; after: 3/80: 3.8%; 2 studies) were similar before and after surgery. Fewer women experienced gestational diabetes after surgery (before: 3/37, 8.1%; after: 0/37; 1 study), and the risk of preeclampsia was similar before and after surgery (before: 2/37, 5.4%; after: 0/37; 1 study). We are very uncertain of the effects of IBD-related surgery on these outcomes due to poor quality evidence, including confounding bias due to increased age of women after surgery.We rated evidence for all outcomes and comparisons as very low quality due to the observational nature of the data, inclusion of small studies with imprecise estimates, and high risk of bias among included studies. AUTHORS' CONCLUSIONS: The effect of surgical therapy for IBD on female infertility is uncertain. It is also uncertain if there are any differences in infertility among those undergoing open versus laparoscopic procedures. Previous surgery was associated with higher risk of miscarriage, use of ART, Caesarean section delivery, and giving birth to a low birth weight infant, but was not associated with risk of stillbirth, preterm delivery, or delivery of a small for gestational age infant. These findings are based on very low-quality evidence. As a result, definitive conclusions cannot be made, and future well-designed studies are needed to fully understand the impact of surgery on infertility and pregnancy outcomes.