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INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: Weconducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases. [ABSTRACT FROM AUTHOR]

Background and Aims: In the United States, little is known about the rates of interval upper gastrointestinal (GI) cancer (possibly missed out) after an esophagogastroduodenoscopy (EGD) is performed. Data from non-US studies reported interval cancer rates of 7–26%. We aimed to study the rate and predictors of interval upper GI cancers in the United States. Methods: Using the random 5% sample of Medicare beneficiaries in the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified patients diagnosed with esophageal or gastric cancer during 2000–2007. EGD performed within 36 months prior to cancer diagnosis was identified using CPT codes. Cancers diagnosed 6–36 months after EGD were defined as interval (vs. detected) cancers. The chi-square test and the multivariate logistic model were used in statistical analysis. Results: Of 751 patients diagnosed with upper GI cancer, 52 patients (6.9%) were diagnosed with interval cancers 6–36 months after EGD. The rate of interval cancers was 5.5% (31/568) for gastroenterologists and 11.5% (21/183) for non-gastroenterologists (p < 0.01). In multivariate logistic regression, EGDs performed by gastroenterologists (vs. non-gastroenterologists: OR 0.46, 95% CI 0.25–0.83) and those in inpatient setting (vs. outpatient: OR 0.53, 95% CI 0.28–0.997) were associated with a lower likelihood of interval cancers. Sensitivity analyses limited to outpatient EGDs or interval cancers 6–30 months after EGDs led to similar results. Conclusions: The rate of interval cancers after EGD is the same as the rate of colonoscopy among Medicare patients in the United States. EGDs performed by gastroenterologists and in in-patient settings were associated with a lesser likelihood of interval cancers. [ABSTRACT FROM AUTHOR]

Background: The magnitude of racial/ethnic and regional differences in the prevalence of inflammatory bowel disease (IBD) in the United States remains largely unknown. Aims: To estimate differences in the prevalence of IBD by race/ethnicity and region. Methods: The Medical Expenditure Panel Survey, a nationally representative survey of US households and medical conditions, was used. A multivariate logistic model was used in statistical analysis. Results: Among 202,468 individuals surveyed during 1996-2007, 316 were diagnosed with IBD (26 Blacks, 21 Hispanics, and 5 Asians). The prevalence of IBD was higher in Whites [Crohn's disease: 154; ulcerative colitis (UC): 89] than Blacks (Crohn's disease: 68; UC: 25), Hispanics (Crohn's disease: 15; UC: 35), and Asians (Crohn's: 45; UC: 40) (all p < 0.05, except for UC in Asians). The differences in Crohn's disease between Whites and minorities and the difference in UC between Whites and Blacks remained significant in multivariate analysis. In multivariate analysis, there was no regional difference in the prevalence of Crohn's disease, but the prevalence of UC was higher in the Northeast than the South (p < 0.05). Conclusions: There were significant racial/ethnic differences in the prevalence of IBD in the USA. The underlying etiology of these differences warrants additional research. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Determining the relative cost-effectiveness between advanced therapeutic options for ulcerative colitis (UC) may optimize resource utilization. We evaluated total cost per response, cost per remission, and cost of safety events for patients with moderately-to-severely active UC after 52 weeks of treatment with advanced therapies at standard dosing. Methods: An analytic model was developed to estimate costs from the US healthcare system perspective associated with achieving efficacy outcomes and managing safety outcomes for advanced therapies approved for the treatment of UC. Numbers needed to treat (NNT) for response and remission, and numbers needed to harm (NNH) for serious adverse events (SAEs) and serious infections (SIs) were derived from a network meta-analysis of pivotal trials. NNT for induction and maintenance were combined with drug regimen costs to calculate cost per clinical remission. Cost of managing AEs was calculated using NNH for safety outcomes and published costs of treating respective AEs. Results: Costs per remission were $205,240, $249,417, $267,463, $365,050, $579,622, $750,200, and $787,998 for tofacitinib 10 mg, tofacitinib 5 mg, infliximab, vedolizumab, golimumab, adalimumab, and ustekinumab, respectively. Incremental costs of SAEs and SIs collectively were $136,390, $90,333, $31,888, $31,061, $20,049, $12,059, and $0 for tofacitinib 5 mg, golimumab, adalimumab, tofacitinib 10 mg, infliximab, ustekinumab, and vedolizumab (reference), respectively. Conclusions: Tofacitinib was associated with the lowest cost per response and cost per remission, while vedolizumab had the lowest costs related to SAEs and SIs. Balancing efficacy versus safety is important when evaluating the costs associated with treatment of moderate-to-severe UC. [ABSTRACT FROM AUTHOR]

Hospitalisation and surgery are considered to be markers of more severe disease in Crohn's disease. These are costly events and limiting these costs has emerged as one rationale for the cost of expensive biologic therapies. The authors sought to review the most recent international literature to estimate current hospitalisation and surgery rates for Crohn's disease and place them in the historical context of where they have been, whether they have changed over time, and to compare these rates across different jurisdictions. It is in this context that the authors could set the stage for interpreting some of the early data and studies that will be forthcoming on rates of hospitalisation and surgery in an era of more aggressive biologic therapy. The most recent data from Canada, the United Kingdom and Hungary all suggest that surgical rates were falling prior to the advent of biologic therapy, and continue to fall during this treatment era. The impact of biologic therapy on surgical rates will have to be analysed in the context of evolving reductions in developed regions before biologic therapy was even introduced. Whether more aggressive medical therapy will decrease the requirement for surgery over long periods of time remains to be proven. [ABSTRACT FROM AUTHOR]

Crohn's disease is an idiopathic chronic intestinal illness that requires specialized medical care for prompt disease diagnosis and appropriate management. Clinicians must accurately interpret and integrate findings from multitude of sources in order to achieve diagnostic certainty. Ileocolonoscopy remains the most relied modality, allowing for a direct mucosal visualization and biopsies for histologic assessments. Serologic markers currently serve an adjunctive role, often utilized in attempts to further subtype patients with indeterminate colitis. Radiologic imaging, such as computed tomography enterography can evaluate the far reaches of the small intestine, while also providing information about penetrating complications and extraintestinal disease manifestations. Treatment options and strategies continue to evolve with new biologic agents and ongoing testing of aggressive "top-down" approaches. In addition, identification of increased colorectal cancer risks in individuals with Crohn's colitis has led to formal surveillance guidelines. The clinical diagnosis and management of Crohn's disease continues to be an area of rapid change and exciting developments. [ABSTRACT FROM AUTHOR]

The article presents insights on a study on the use of algorithmic approach in community gastroenterology practices for decreasing the risk of Crohn's disease-related complications. Topics covered include the division of community practices to an algorithmic approach of early combined immunosuppression (ECI) and conventional management of the disease, the key predictors of development of serious Crohn's-related complications and the limitations of the study.

A rising trend in the incidence and prevalence of inflammatory bowel disease (IBD) in Asia has been recognized for the past two decades. It has been postulated that this phenomenon may be related to the westernization of lifestyles, including changes in dietary habits and environmental changes such as improved sanitation and industrialization. Previously we reported that the incidence and prevalence rates of IBD in Asia were low compared with the West, but there was a notably rising secular trend. In this review, we summarize the recent epidemiological data in Asia, characterize the clinical features, risk factors and genetic susceptibility of Asian IBD patients, and compare these to those of Western IBD patients. In the past decade, the incidence and prevalence of IBD reported across Asia, particularly in East Asia, has continued to increase. Familial clustering is generally uncommon in East Asia but appears to be higher in West Asia. The genetic susceptibilities in Asian IBD patients differ from those of White patients, as NOD2/CARD15 mutations are much less common. The clinical phenotypes and complication rates of Asian IBD resemble the White population in general, but with some differences, including lower surgical rates, higher prevalence of males, and higher prevalence of ileocolonic involvement among East Asian Crohn's disease patients, and a low frequency of primary sclerosing cholangitis among IBD patients in East and Southeast Asia. [ABSTRACT FROM AUTHOR]

PURPOSE: We sought to describe the types of colectomy, follow-up surgical/diagnostic procedures, and complications occurring within 180 days of colectomy in a population of privately insured individuals with ulcerative colitis (UC). METHODS: This was a retrospective analysis of claims data of privately insured patients (MarketScan) for the years 2001–2004. We identified a cohort of patients with UC who underwent colectomy. Colectomies were classified into four categories based on the surgery occurring on the first colectomy date: (a) total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA), (b) subtotal colectomy (SC) with ileostomy and Hartmann pouch or ileorectal anastomosis, (c) TPC with ileostomy, and (d) partial colectomy (PC). Follow-up surgical/diagnostic procedures and complications were compared across colectomy categories. RESULTS: A total of 25,586 UC patients were identified, of whom 215 patients had a colectomy and at least 180 days of pre- and postcolectomy follow-up. The colectomy distribution was: TPC-IPAA (52%), SC-ileostomy (22%), TPC-ileostomy (14%), and PC (13%). Within 180 days postcolectomy, 54% of patients had a second colectomy-related surgery (including unplanned surgeries in 15.3%), and 27% had a follow-up diagnostic procedure. Postcolectomy complications included abscesses (11.6% in the first 30 days postcolectomy, 16.3% in the day 31–180 postcolectomy period), fistulas (4.2% early, 6.0% late), and sepsis/pneumonia/bacteremia (7.9% early, 9.3% late). CONCLUSION: Postcolectomy surgical procedures and complications occur frequently after colectomy in privately insured patients with UC. [ABSTRACT FROM AUTHOR]

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. Design and setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). Main outcome measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a serious complication of inflammatory bowel disease. Given this fact, it is necessary to examine the opportunities for current and future approaches to colorectal cancer prevention. The value of surveillance colonoscopy and chemoprevention of colorectal cancer with 5′-aminosalicylic acid has been evaluated in the recent literature. The current state of knowledge in the epidemiology of and new approaches to the prevention of cancer and dysplasia in inflammatory bowel disease were reviewed. It is concluded that there is significant preclinical and clinical evidence to suggest that 5-aminosalicylate drugs reduce the risk of colorectal neoplasia. However, the minimal dosage to achieve this chemopreventive effect remains unclear. There is also indirect evidence to suggest that surveillance colonoscopy is beneficial for patients with inflammatory bowel disease, particularly in those with long-standing pancolitis or primary sclerosing cholangitis-associated inflammatory bowel disease. However, definitive proof from prospective clinical trials is not available. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVES:Most reports of fistulas to the urinary system in Crohn’s disease are relatively small. We sought to describe the clinical features and outcomes of these patients.METHODS:A centralized diagnostic index identified all Crohn’s disease patients with urinary tract fistulas who were evaluated at our institution between 1976 and 2000. Medical records were abstracted for patient demographics, presenting symptoms, diagnostic tests, and all therapies.RESULTS:A total of 78 patients (56% men) were identified. Patients presented with pneumaturia (68%), dysuria (64%), recurrent urinary tract infections (32%), and fecaluria (28%). Cystoscopy and CT of the abdomen/pelvis had the highest diagnostic yield (74% and 52%, respectively). Fistulas originated from the ileum (64%), colon (21%), rectum (8%), and multiple sites (7%). Urinary tract sites included bladder (88%), urethra (6%), urachus (3%), ureter (1%), and other (1%). Median follow-up was 1.1 yr (0–22.3 yr). A total of 70 patients (90%) had surgery, with medical treatment first attempted in four patients with antibiotics and/or immunosuppressants. One patient had adequate symptom relief without surgery on antibiotic suppression alone. Six patients required a partial cystectomy, but no patient had a cystectomy or nephrectomy. Only three surgical patients had recurrent urinary system fistulas.CONCLUSIONS:Urinary tract fistulas in Crohn’s disease occurred more often in men. Patients with these fistulas presented with pneumaturia, dysuria, recurrent infections, and fecaluria. The most helpful diagnostic tests were cystoscopy and CT of abdomen/pelvis. Surgery resulted in durable remission. Medical therapy for these fistulas deserves further study. [Copyright &y& Elsevier]

OBJECTIVES:Nonsteroidal anti-inflammatory drugs (NSAIDs) are relatively contraindicated in patients with inflammatory bowel disease (IBD) for fear of disease aggravation. Cyclooxygenase-2 inhibitors have fewer GI side effects than traditional NSAIDs in unselected patients. We report the safety of these agents in patients with IBD.METHODS:Patients with Crohn’s disease, ulcerative colitis, or pouchitis who used celecoxib or rofecoxib were identified from computerized prescription records. A retrospective chart review was conducted. Concomitant medications, past NSAID use, indication for cyclooxygenase-2 inhibitor, dose, and duration were obtained. IBD disease activity before cyclooxygenase-2 inhibitor use was graded using a modified disease activity index. Change in disease activity was graded as improved, no change, or worsened. Patients were contacted to provide data not found in the charts. The proportion of patients receiving cyclooxygenase-2 inhibitors who experienced exacerbation of IBD was determined.RESULTS:Eleven patients were treated with celecoxib (median dose = 200 mg/day), and 16 patients were treated with rofecoxib (median dose = 25 mg/day). Median duration of therapy was 9 months (range = 1 wk-22 months). The drug was beneficial in 14 patients, of partial benefit in eight, and of no benefit in five. Two patients (7.4%) (95% CI = 2–23%) had aggravations of IBD. Three patients (11%) had other adverse events (renal insufficiency, rash, and asymptomatic colonic ulceration). All adverse events were reversible.CONCLUSIONS:Our preliminary results suggest that cyclooxygenase-2 inhibitors may be safe and beneficial in most patients with IBD. A placebo-controlled trial to confirm these preliminary observations is needed. [Copyright &y& Elsevier]

OBJECTIVE:The optimal strategy for the management of definite low grade dysplasia (LGD) detected in surveillance in ulcerative colitis (UC) is unknown, because the natural history of LGD has not been well described.METHODS:We reviewed the Mayo Clinic records of patients with UC found to have flat LGD between 1990 and 1993 in whom a nonoperative strategy was pursued for 2 months or more.RESULTS:Eighteen patients with UC and LGD were observed for a median of 32 months. Nine of 18 patients identified with UC and LGD developed advanced neoplastic lesions during follow-up, which were defined as adenocarcinoma, raised dysplasia, or high grade dysplasia. The cumulative incidence of progression to an advanced lesion was 33% at 5 yr (95% CI = 9–56%). Only one patient developed adenocarcinoma, diagnosed 74 months after his initial finding of LGD and 20 months after his last surveillance exam. Besides this patient, adenocarcinoma was not detected in the colectomy specimens of 13 other patients who underwent surgery. Colectomies were performed for dysplasia or cancer in seven patients, active colitis in five patients, and unknown reasons in two patients. Four patients did not have colectomies.CONCLUSIONS:Neoplastic progression in patients with UC and LGD is common. Total proctocolectomy should be offered to all patients with flat LGD. Our study illustrates numerous pitfalls in the practice of surveillance. [Copyright &y& Elsevier]

INTRODUCTION: Limited data exist evaluating antiobesity medications (AOM) in patients with inflammatory bowel disease (IBD). METHODS: We performed a case-control study evaluating the effectiveness and safety of AOM in patients with IBD with obesity, matched to non-IBD controls. RESULTS: After 12 months, the case (n = 36) and control (n = 36) groups achieved similar percent total body weight loss of -6.9 ± 8.3 and -8.1 ± 7.0 (P = 0.30), respectively. Side effect profiles were similar between groups. Seven patients experienced an IBD flare, all managed medically. DISCUSSION: AOM use in patients with IBD demonstrated similar effectiveness and safety when compared with that observed in the non-IBD population. [ABSTRACT FROM AUTHOR]

The decision to use opioid analgesics in the management of chronic pain in patients with Crohn's disease is a complex one. Little is known about the effects of long-term high-dose opioids on cognitive function or risk of opioid addiction. At higher doses, opioids affect the gastrointestinal tract adversely and may result in perturbations of the endocrine and immune systems. Distinguishing functional gastrointestinal symptoms from inflammatory symptoms can further complicate this issue. Cross and colleagues have attempted in a retrospective cross-sectional study to identify factors which may predict narcotic use in patients with Crohn's disease. Increased disease activity, polypharmacy (particularly with neuropsychiatric drugs) and cigarette smoking were found to be independent predictors of chronic narcotic use in these patients. Future research in this area is greatly needed to improve patient care. In patients with Crohn's disease, caution should be exercised when it comes to the liberal use of narcotics. [ABSTRACT FROM AUTHOR]

This article focuses on matters related to understanding tests of heterogeneity in metaanalysis. A case scenario is presented of an 18-yr-old woman with right lower quadrant abdominal discomfort, unintentional 5-pound weight loss and intermittent diarrhea for the past 3 months. Initial evaluation reveals mild normocytic anemia, elevated ESR and stool cultures with normal flora. Small bowel follow through demonstrates a structure of the distal 15 cm of the ileum. Colonoscopy reveals inflammation in the terminal ileum and biopsies are consistent with Crohn's disease. The patient is started on prednisone 40 mg daily and the dose is tapered over 8 wk.

Background: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridioides difficile infection (CDI) with an increased risk of adverse outcomes including increased in-hospital mortality, IBD treatment failure, re-hospitalization, and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors [body mass index (BMI), statin use, opioid use, and antidepressant use] on CDI risk and adverse outcomes in these patients. Methods: Using a retrospective design, variables were abstracted from records for patients with IBD and CDI from 2008 to 2013. Statistical analysis comprised descriptive statistics and univariate and multivariate logistic regression analyses. Results: There were 137 patients with IBD and CDI included in this study. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe, complicated CDI, compared with 22% of patients in the underweight/normal BMI [odds ratio (OR) 2.85, p = 0.02] and 19% in the obese category (OR 3.95, p = 0.04). Statin use was associated with severe or severe, complicated CDI when controlling for age and BMI (OR 5.66, p = 0.01). There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Conclusions: An overweight BMI and statin use were associated with severe or severe, complicated CDI in IBD patients. Further studies are needed to better understand how these factors impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of complications from CDI. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridioides difficile infection (CDI) with an increased risk of adverse outcomes including increased in-hospital mortality, IBD treatment failure, re-hospitalization, and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors [body mass index (BMI), statin use, opioid use, and antidepressant use] on CDI risk and adverse outcomes in these patients. Methods: Using a retrospective design, variables were abstracted from records for patients with IBD and CDI from 2008 to 2013. Statistical analysis comprised descriptive statistics and univariate and multivariate logistic regression analyses. Results: There were 137 patients with IBD and CDI included in this study. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe, complicated CDI, compared with 22% of patients in the underweight/normal BMI [odds ratio (OR) 2.85, p = 0.02] and 19% in the obese category (OR 3.95, p = 0.04). Statin use was associated with severe or severe, complicated CDI when controlling for age and BMI (OR 5.66, p = 0.01). There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Conclusions: An overweight BMI and statin use were associated with severe or severe, complicated CDI in IBD patients. Further studies are needed to better understand how these factors impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of complications from CDI. [ABSTRACT FROM AUTHOR]

Background: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking.Methods: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52.Results: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years.Conclusions: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.). [ABSTRACT FROM AUTHOR]

Examines imaging and therapy for perianal Crohn's disease. Need for an aggressive and multimodal approach in the preservation of the anorectum; Inaccuracy of barium fistulography for perianal disease; Comparison of endoscopic ultrasound, magnetic resonance imaging and examination under anesthesia.

Background: Tumor necrosis factor (TNF)-α inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome.Methods: We performed a systematic review of the English-language literature to investigate if treatment with TNF-α blockers during pregnancy in women with IBD increases the risk of spontaneous abortions, preterm delivery, stillbirth, low birth weight, congenital malformations, or risk of infections in the offspring. Of 552 articles and abstracts reviewed, 58 articles or abstracts with unique content were identified and included in this systematic review. However, most presentations were case reports or case series supplied by a limited number of observational studies. No randomized controlled studies were available.Results: TNF-α inhibitors do not seem to affect either outcome of pregnancy in mothers with IBD, or the outcome in the offspring (congenital malformations and immunosuppression). Further, recent data have not identified any increased risk of infections in the first year of life in the offspring of mothers who received biologics, even in combination with immunomodulators (thiopurines).Conclusions: From the present systematic review, no association was found between administration of TNF inhibitors for IBD during pregnancy and adverse pregnancy outcome or congenital abnormalities. Further, no increased relative risk of infections has been reported in the first year of life in offspring of mothers who received biologics. Biologics should be discontinued during pregnancy solely if the IBD is in remission using the same stopping criteria as for patients with IBD in general, as uncontrolled activity of IBD may expose the mother and child to a risk greater than those only potentially coming from the use of TNF-α inhibitors. In such cases, inoculation of the offspring with live vaccines is contraindicated until the biologic agent is no longer detectable in the child's circulation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with ulcerative colitis (UC) regard rapid onset of action among the most important aspects of their treatment. We used the partial Mayo Clinic Score (pMCS) and component patient-reported subscores to assess the rapidity and sustainability of response to filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, in adults with moderately to severely active UC in the phase 2b/3 SELECTION trial. The association between early symptomatic improvements and health-related quality of life (HRQoL) outcomes was also assessed. METHODS: In these post hoc analyses of the double-blinded, randomized, placebo-controlled 58-week SELECTION trial (NCT02914522), rectal bleeding and stool frequency diary data on days 1–15 and pMCS remission and response at multiple time points including weeks 10 and 58 were evaluated. HRQoL was assessed using the Inflammatory Bowel Disease Questionnaire at weeks 10 and 58. RESULTS: Filgotinib 200 mg relative to placebo improved rectal bleeding and stool frequency within 7 days (P < 0.05). By week 2, greater proportions of filgotinib 200 mg-treated patients than placebo-treated patients achieved pMCS remission (biologic-naive, 15.1% vs 8.0%, P = 0.0410; biologic-experienced, 10.3% vs 4.2%, P = 0.0274). A similar treatment effect was observed at week 58 (P < 0.0001). Day 7 rectal bleeding and stool frequency subscores were associated with the Mayo Clinic Score response at weeks 10 and 58. Patients in pMCS remission at weeks 10 and 58 had greater improvements in the Inflammatory Bowel Disease Questionnaire score than those not in pMCS remission. DISCUSSION: Filgotinib 200 mg daily resulted in rapid and sustained improvements in both UC symptoms and HRQoL. [ABSTRACT FROM AUTHOR]

A response by Darell S. Pardi and colleagues to a letter to the editor about their article "The epidemiology of microscopic colitis: a population-based study in Olmsted County, Minnesota" in the previous issue is presented.

Microscopic colitis, a chronic diarrheal condition, is characterized by colonic intraepithelial lymphocytosis, expansion of the lamina propria with acute and chronic inflammatory cells, and preserved crypt architecture. These changes, in association with a thickened subepithelial collagen band, are termed collagenous colitis, whereas changes occurring without a thickened collagen band are classified as lymphocytic colitis. Population-based epidemiologic studies confirm that microscopic colitis is most frequently diagnosed in middle-aged or elderly women and that its incidence is rising. Although these disorders diminish patients'' quality of life, they are not associated with an increased risk of colorectal cancer, and survival is not diminished. Clinical and histologic improvement after therapy have been noted in one randomized trial of bismuth subsalicylate and three randomized clinical trials of oral delayed-release budesonide. A treatment algorithm for microscopic colitis is proposed. [Copyright &y& Elsevier]

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7–60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = −3.9%; 95% CI: −4.4, −3.3) and morality rates (AAPC = −4.7%; 95% CI: −5.6, −3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum. [ABSTRACT FROM AUTHOR]

Background/Aims: The benefits of colonoscopy in reducing colorectal cancer (CRC) risk for patients over 75 years are controversial. We aimed to determine whether colonoscopy use is associated with a decreased risk of CRC in patients 76-85 years old in the United States (US). Patients and Methods: All patients in the Medicare 5% random sample of the Surveillance, Epidemiology and End Results-Medicare linked database 76-85 years old at outpatient colonoscopy between January 1, 1998 and December 31, 2002 were identified. Using the Kaplan-Meier method, we estimated the cumulative incidence of CRC in the above-mentioned colonoscopy group and compared with the control group of patients without colonoscopy. All patients were followed until diagnosis of CRC or carcinoma in situ, death or December 31, 2005. The multivariate Cox proportional hazards model was used in statistical analysis. CRC was separated by location into distal vs. proximal CRC in subgroup analysis. Results: Of 5,701 patients in the colonoscopy group, 37 (0.65%) patients were diagnosed with CRC, compared to 379 (1.55%) out of 24,437 patients in the control group (p < 0.001). The cumulative incidences of distal and proximal CRC were lower in the colonoscopy group compared to those in the control group (5-year distal CRC: 0.26 vs. 0.77%; 5-year proximal CRC: 0.43 vs. 0.79%, both p < 0.05). In multivariate Cox regression, colonoscopy was associated with decreased risk of all CRC (hazard ratio ((HR) 0.42, 95% CI 0.28-0.65), distal CRC (HR 0.36, 95% CI 0.18-0.70), and proximal CRC (HR 0.53, 95% CI 0.30- 0.92)). Conclusion: Among patients 76-85 years old in the United States, colonoscopy use was associated with decreased risks of both distal and proximal CRC, with a smaller risk reduction in distal colon. Due to inherent limitations associated with our retrospective design, future prospective studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Patients with longstanding inflammatory bowel disease (IBD) involving large intestine proximal to rectum are considered to be at increased risk for colorectal cancer (CRC). One prior study showed low utilization of surveillance colonoscopy in patients with ≥8 years of ulcerative colitis (UC) in the USA. Aims: To study use of surveillance colonoscopy among Medicare beneficiaries with IBD in the 2-year period prior to CRC diagnosis. Data and Methods: Our study sample included Medicare beneficiaries in the SEER-Medicare-linked database who were diagnosed with CRC during 2001-2005 and had ≥3 physician visits with ICD-9 diagnosis code for IBD prior to CRC diagnosis. Medicare beneficiaries aged >85 years without Part B coverage or enrolled in HMOs were excluded. Colonoscopy performed within 6-30 months prior to CRC diagnosis was defined as surveillance colonoscopy. The χ2 test and multivariate logistic regression were used in statistical analysis. Results: Of 241 Medicare beneficiaries with IBD and diagnosed with CRC, 92 (38%) patients underwent ≥1 surveillance colonoscopy in the 2 years prior to cancer diagnosis. The use of surveillance colonoscopy was similar between Crohn's disease (28/86, 33%) and UC (64/155, 41%). In multivariate logistic regression, older age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-0.99) was negative associated with surveillance colonoscopy use and personal history of colon polyp (OR 2.73, 95% CI 1.09-6.87) was positively associated with surveillance colonoscopy use. Conclusions: Use of surveillance colonoscopy was low among Medicare beneficiaries with IBD in the 2 years prior to CRC diagnosis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aim: Inflammatory bowel diseases (IBD) have been associated with increased risk of cardiovascular events. We aimed to investigate the outcomes of myocardial infarction (MI) in patients with IBD. Methods: We performed a cross-sectional study utilizing data from the Nationwide Inpatient Sample from the years 1998 to 2010. ICD-9-CM codes were used to identify patients with Crohn's disease (CD) (555.X), ulcerative colitis (UC) (556.X), and acute MI (410.X). Outcomes in patients with MI with and without IBD were compared. Univariate analysis was performed. Multivariate logistic regression was used to determine the effect of UC and CD on in-hospital MI mortality after adjusting for confounders. Results: A total of 2,629,161 MI, 3,607 UC and 3784 CD patients were analyzed. UC (odds ratio [OR], 1.12; 95% CI 0.98–1.29) and CD (OR 0.99; 95% CI 0.86–1.15) did not affect in-hospital mortality in patients with MI. There was no difference between in-hospital mortality in patients with MI with or without UC (7.75% vs. 7.05%; p = 0.25) or in patients with MI with or without CD (6.50% vs. 6.59%; p = 0.87). The length of stay (LOS) was higher in IBD patients and total charges were statistically higher in patients with UC as compared to non-IBD patients ($65,182 vs. $53,542; p < 0.001). Conclusions: This study shows that IBD does not impact in-hospital mortality from MI. However, patients with MI with IBD have longer LOS. Patients with UC have higher total hospitalization charges than patients with MI without IBD. Further prospective studies are needed to assess the outcomes of MI in IBD patients. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1–10 (1 5 strongly disagree and 10 5 strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous.During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. Itwas recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10–15 mg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti–tumor necrosis factor therapy. It was recommended to perform proactive TDMafter induction and at least once during maintenance. Consensus was achieved inmost cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti–tumor necrosis factors. [ABSTRACT FROM AUTHOR]

: ObjectivesThe occurrence of Crohn''s disease (CD) in a patient with an ileal-pouch anstomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients.: MethodsMedical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1–16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions.: ResultsAt a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3–44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab.: ConclusionsInfliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients. [Copyright &y& Elsevier]

OBJECTIVE:There are no reports of the clinical features or treatment outcomes in large series of patients with lymphocytic colitis, and it is not known whether treatments that appear to be beneficial in patients with collagenous colitis are also beneficial in lymphocytic colitis. We sought to analyze these issues in our patients with lymphocytic colitis.METHODS:All patients with biopsy-proven lymphocytic colitis evaluated at our institution between January 1, 1997, and December 31, 1999, were identified. Clinical features on presentation and treatment outcomes were abstracted from the medical records.RESULTS:A total of 170 patients with lymphocytic colitis were identified (median age 67 yr, 61% female). Diarrhea, bloating, rectal urgency, fecal incontinence, weight loss, concomitant autoimmune disorders, and aspirin or nonsteroidal anti-inflammatory drug use were common. Loperamide, diphenoxylate/atropine, and bismuth subsalicylate were effective therapies and were well tolerated. However, no therapy produced a complete response in more than 40% of patients.CONCLUSIONS:Lymphocytic colitis typically presents in elderly patients as chronic diarrhea. Nocturnal stools, urgency, and abdominal pain occur frequently, as do weight loss, fecal incontinence, and concomitant autoimmune disorders. Many empiric treatment options are used, but overall response rates are disappointing. Randomized controlled trials are needed to determine the optimum therapeutic approach to these patients. [Copyright &y& Elsevier]

The inflammatory bowel diseases (IBD), which consist of Crohn's disease and ulcerative colitis, are chronic, incurable immunemediated inflammatory disorders of the intestine. As IBD incidence continues to increase globally and its mortality is low, prevalent cases of IBD are rapidly increasing, thereby leading to a substantial increase in health care costs. Although the introduction of biologic agents for IBD management has revolutionized the armamentarium of IBD therapy, the high cost of this therapy is concerning. With the expirations of patents for existing biologic agents (originals), biosimilars with cheaper costs have been highlighted in the field of IBD. Despite concerns regarding their short- and long-term efficacy, safety, immunogenicity, and interchangeability, increasing evidence via prospective observations and phase III or IV clinical trials, which aim to prove the "biosimilarity" of biosimilars to originals, has partly confirmed their efficacy, safety, and interchangeability. Additionally, although patients and physicians are reluctant to use biosimilars, a positive budget impact has been reported owing to their use in different countries. In the near future, multiple biosimilars with lower costs, and efficacy and safety profile similar to originals, could be used to treat IBD; thus, further consideration and knowledge dissemination are warranted in this new era of biosimilars. [ABSTRACT FROM AUTHOR]

The changing epidemiology of inflammatory bowel disease (IBD) across time and geography suggests that environmental factors play a major role in modifying disease expression. Disease emergence in developing nations suggests that epidemiological evolution is related to westernisation of lifestyle and industrialisation. The strongest environmental associations identified are cigarette smoking and appendectomy, although neither alone explains the variation in incidence of IBD worldwide. Urbanisation of societies, associated with changes in diet, antibiotic use, hygiene status, microbial exposures and pollution have been implicated as potential environmental risk factors for IBD. Changes in socioeconomic status might occur differently in different geographical areas and populations and, consequently, it is important to consider the heterogeneity of risk factors applicable to the individual patient. Environmental risk factors of individual, familial, community-based, countrybased and regionally based origin may all contribute to the pathogenesis of IBD. The geographical variation of IBD provides clues for researchers to investigate possible environmental aetiological factors. The present review aims to provide an update of the literature exploring geographical variability in IBD and to explore the environmental risk factors that may account for this variability. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The Crohn's Disease Activity Index (CDAI) is used to judge efficacy in clinical trials. We explored the effect of CDAI response definitions for induction on study efficiency. METHODS: We analyzed primary CDAI data from induction studies in patients with mildly to moderately active Crohn's disease, not receiving concomitant aminosalicylates, corticosteroids, or immunomodulator therapy, and without fistulizing or stricturing complications. The 12 definitions of clinical response included: CDAI decrease from baseline by 50, 70, 100, or 150 points; decrease by 25% from baseline and by 70 or 100 points; CDAI <100 or 150 points; CDAI <150 points plus decrease by 70 or 100 points; CDAI <150 points at any time sustained for the duration of the trial; or decrease in the CDAI by 70 points for the last two consecutive visits. Response definitions were ranked according to ability to optimize the effect difference between treatment arms. The effect of time, baseline disease activity (CDAI 200–299 or ≥300 points), and previous surgical resections on response definitions were evaluated and ranked. Multivariate analysis on additional factors of age (<40 or ≥40 yr), gender and duration of disease (<2 or ≥2 yr) were performed to determine predictors of response when applied to these CDAI definitions. RESULTS: Treatment effect differences in placebo-controlled studies were maximized by response definitions that incorporated either a decrease CDAI ≥70 points for the last two consecutive visits or decrease in baseline CDAI ≥100 points, and remained optimal when evaluated for the composite effect of time, baseline activity, and prior resections. A decrease in baseline CDAI ≥100 points had some advantages over a decrease CDAI ≥70 points over two visits in terms of study efficiency, as it produced a lower control response rate and was not influenced by any of the baseline factors. CONCLUSION: Clinical trial efficiency for induction studies in patients with mildly to moderately active Crohn's disease can be improved by using either a decrease in CDAI by ≥70 points for the last two consecutive visits or a decrease in baseline CDAI by ≥100 points as the primary end point for the trial. These findings are valid for patients with ileocecal Crohn's disease not refractory to aminosalicylates, corticosteroids, immunomodulators, and biologics, and patients who do not have stricturing or penetrating complications. It is unclear if these CDAI response criteria would similarly increase study efficiency in trials that recruited patients with moderately to severely active disease, patients refractory to aminosalicylates, corticosteroids, immunomodulators, and biologics, and patients with stricturing or penetrating complications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: For diagnosis, assessing disease activity, complications and extraintestinal manifestations, and monitoring response to therapy, patients with inflammatory bowel disease undergo many radiological studies employing ionizing radiation. However, the extent of radiation exposure in these patients is unknown. METHODS: A population-based inception cohort of 215 patients with inflammatory bowel disease from Olmsted County, Minnesota, diagnosed between 1990 and 2001, was identified. The total effective dose of diagnostic ionizing radiation was estimated for each patient. Linear regression was used to assess the median total effective dose since symptom onset. RESULTS: The number of patients with Crohn's disease and ulcerative colitis was 103 and 112, with a mean age at diagnosis of 38.6 and 39.4 yr, respectively. Mean follow-up was 8.9 yr for Crohn's disease and 9.0 yr for ulcerative colitis. Median total effective dose for Crohn's disease was 26.6 millisieverts (mSv) (range, 0–279) versus 10.5 mSv (range, 0–251) for ulcerative colitis ( P < 0.001). Computed tomography accounted for 51% and 40% of total effective dose, respectively. Patients with Crohn's disease had 2.46 times higher total effective dose than ulcerative colitis patients ( P= 0.001), adjusting for duration of disease. CONCLUSIONS: Annualizing our data, the radiation exposure in the inflammatory bowel disease population was equivalent to the average annual background radiation dose from naturally occurring sources in the U.S. (3.0 mSv). However, a subset of patients had substantially higher doses. The development of imaging management guidelines to minimize radiation dose, dose-reduction techniques in computed tomography, and faster, more robust magnetic resonance techniques are warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The relationship between abnormal hepatic biochemistries and inflammatory bowel disease (IBD) is unclear. We determined the prevalence of abnormal hepatic biochemistries and chronic liver disease in a cohort of IBD patients, and we compared patients with normal and abnormal liver biochemistries. METHODS: Patients with IBD evaluated at our institution between January 1, 2000 and December 31, 2000 were identified. Data on gender, age, IBD subtype, extent and activity, medications, liver disease history, liver biochemistries, and vital status were collected. The χ2 test, Student's t-test, and Cox proportional regression were used. RESULTS: We identified 544 patients with available hepatic biochemistries. Abnormal hepatic biochemistries were found in 159 (29%). Defined chronic liver disease was present in 5.8% of patients (primary sclerosing cholangitis in 4.6%). The prevalence of abnormal hepatic biochemistries was 27% for those with active IBD and 36% for those in remission ( P= 0.06). Patients with abnormal hepatic biochemistries were less frequently on 5-aminosalicylates (35% vs 51%, P < 0.001), and a smaller proportion was alive at last follow-up (90.4% vs 98.5%, P < 0.0001). The age-adjusted risk of death was 4.8 times higher in patients with abnormal hepatic biochemistries, after excluding patients with any diagnosis of liver disease. CONCLUSIONS: Abnormal hepatic biochemistries were present in nearly one-third of our patients, and surprisingly, they were not associated with IBD activity. Abnormal hepatic biochemistries and chronic liver disease appeared to have a negative impact on vital status. Persistently abnormal hepatic biochemistries should be evaluated, and not attributed to IBD activity. [ABSTRACT FROM AUTHOR]