Marjorie Merrick

Fatigue is highly associated with poor health‐related quality of life, disability and depression in newly‐diagnosed patients with inflammatory bowel disease, independent of disease activity

Fatigue is common in Crohns disease (CD) and ulcerative colitis (UC). Data on fatigue in newly diagnosed patients are unavailable.

Challenges in IBD Research: updating the scientific agendas.

Substantial progress has been made since the first “Challenges in IBD Research” white paper was drafted in 1990. Advances in basic science—particularly in immunology, genetics, epithelial cell biology, signal transduction, molecular biology, and other areas—have added greatly to our understanding of disease pathogenesis and have identified many new targets for therapeutic intervention. One important realization that has emerged in the past few years is that a complex and active communication among the bacterial flora, epithelium, and immune cells exists in the intestine and that perturbation of these interactions can result in chronic intestinal inflammation. Thus, the major working hypothesis, particularly coming from basic research in experimental models, is that inflammatory bowel disease (IBD) is due to an abnormal cell-mediated immune reaction—primarily by CD4 T cells—to the antigens and adjuvants of the enteric bacteria in genetically susceptible hosts. Consequently, many of the priorities and associated resources are directed at gaining a better understanding of the interactions between enteric bacteria and the host as well as the regulation of T-lymphocyte activation and differentiation. Powerful new technologies are now available to define the molecular and genetic basis of complex diseases such as ulcerative colitis and Crohn’s disease. These technologies must be applied to clinical studies of patients, i.e., to define subsets of patients with common molecular and/or genetic features. One emerging theme of the 2002 meeting in Phoenix was that there must be closer integration of laboratory-based and clinical investigators to take advantage of these powerful new technologies. A second overriding theme was a focus on disease prevention by both laboratory-based and clinical investigators. One goal for basic research is the achievement of sufficient knowledge and understanding of disease pathogenesis to frame strategies to prevent the onset or recurrence of disease in genetically susceptible individuals, and one goal for clinical research is to develop better treatments for the prevention of relapse in patients who have achieved remission through medical therapy or surgery. Prevention of IBD will require the combined efforts of both laboratory-based and clinical investigators. Many worthy avenues of research were considered and discussed. The leading basic and clinical research priorities at the present time are the following:

Menstrual cycle changes in women with inflammatory bowel disease: a study from the ocean state Crohn's and colitis area registry.

Background:The effect of the inflammatory bowel diseases (IBD) on menstrual function is largely unknown. The aims of this study were to determine whether changes in menstrual function occur in the year before IBD diagnosis or in the initial years after diagnosis. Methods:Women aged 18 years and older in the Ocean State Crohns and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. Menstrual cycle characteristics were retrospectively assessed. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes. Results:One hundred twenty-one patients were studied. Twenty-five percent of patients experienced a change in cycle interval in the year before IBD diagnosis and 21% experienced a change in the duration of flow. Among women with dysmenorrhea, 40% experienced a change in the intensity of their menstrual pain and 31% experienced a change in its duration. Overall cycle regularity increased over time. Quality of life was significantly lower in women without regular cycles across all time points. Conclusions:Changes in menstrual function occur frequently in the year before IBD diagnosis; therefore, screening for menstrual irregularities should be considered in women with newly diagnosed IBD. Patients can be reassured that cycles typically become more regular over time.

Body image dissatisfaction in patients with inflammatory bowel disease.

Background:Despite the fact that the inflammatory bowel diseases (IBD) and their treatments may affect physical appearance, the effect of IBD on body image is poorly understood. The aims of this study were to determine whether body image dissatisfaction (BID) changes over time in patients with IBD and to examine the demographic and disease-related variables associated with decreased body image. Methods:Adults aged 18 and above in the Ocean State Crohns and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. BID was assessed using a modified version of the Adapted Satisfaction With Appearance questionnaire. Total Adapted Satisfaction With Appearance scores and 2 subscores were calculated. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes. Results:Two hundred seventy-four patients were studied. BID was found to be stable over time among men and women with IBD despite overall improvements in disease activity. No differences were found in BID according to IBD subtype. Female gender, greater disease activity, higher symptom burden, longer duration of steroid use, dermatologic and musculoskeletal manifestations of IBD, and ileocolonic disease location among patients with Crohns disease were associated with greater BID. Greater BID was associated with lower health-related quality of life. Conclusions:BID remains stable in an incident cohort of IBD despite improved disease activity and is associated with lower health-related quality of life.

Serum Proteome Profiles in Stricturing Crohn's Disease: A Pilot Study.

Background:Crohns disease (CD) is a form of inflammatory bowel disease with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of inflammatory bowel disease. We performed a pilot study to examine differences in the proteome among patients with stricturing CD, nonstricturing CD, and ulcerative colitis. Methods:Serum samples were selected from the Ocean State Crohns and Colitis Area Registry, an established cohort of patients with inflammatory bowel disease. Patients with CD with surgically resected stricture were matched with similar patients with CD without known stricture and with ulcerative colitis. Serum samples from each patient were digested and analyzed using liquid chromatography–mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture. Results:Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the 3 groups. We quantified 7668 peptides and 897 proteins for analysis. Receiver operating characteristic analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides and determined their function based on previously published literature. Conclusions:The serum of patients with stricturing CD, nonstricturing CD, and ulcerative colitis is distinguishable through proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.

Incidence of Crohn's Disease and Ulcerative Colitis in Rhode Island: Report from the Ocean State Crohn's and Colitis Area Registry.

Background:Studies describing the incidence of Crohns disease (CD) and ulcerative colitis (UC) are uncommon in the United States. We sought to determine the incidence of CD and UC in the state of Rhode Island. Methods:The Ocean State Crohns and Colitis Area Registry is a state-based inception cohort of patients newly diagnosed with inflammatory bowel disease (IBD) in Rhode Island. To confirm a diagnosis of CD, UC, or IBD unclassified (IBDU), the National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium criteria were applied in a review of medical records from gastroenterology practices located in the state of Rhode Island and adjacent to the Rhode Island border in Massachusetts and Connecticut. Using population-based data, we determined the statewide incidence of IBD in Rhode Island from 2008 to 2010. Results:A total of 971 Rhode Island residents were diagnosed with IBD, including 444 with CD, 486 with UC, and 41 with IBD unclassified from 2008 to 2010. The overall age- and sex-adjusted IBD incidence was 30.2 (95% confidence interval, 28.3–32.1) per 100,000 persons in this time frame with 13.9, 15.1, and 1.3 per 100,000 diagnosed with CD, UC, and IBD unclassified, respectively. Of the total incident cases in Rhode Island, 30% (n = 291) were enrolled in Ocean State Crohns and Colitis Area Registry for follow-up. Conclusions:The incidence of IBD in Rhode Island is higher than that previously reported by other population-based cohorts in the United States. Prospective follow-up of individuals enrolled in the community-based Ocean State Crohns and Colitis Area Registry cohort is ongoing.

Testing for Clostridium difficile in Patients Newly Diagnosed with Inflammatory Bowel Disease in a Community Setting

Background:The incidence of Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) is increasing, and CDI has a negative impact on IBD outcomes with both increased morbidity and mortality. Data are lacking regarding the rate of appropriate testing for CDI at the time of diagnosis. Methods:We sought to determine the rate of CDI testing and CDI positivity at diagnosis of IBD using data collected through the Ocean State Crohns and Colitis Area Registry (OSCCAR), a prospective cohort of patients with newly diagnosed IBD. CDI testing and CDI positivity were determined by reviewing the medical records of patients enrolled into the registry and diagnosed with IBD between January 2008 and July 2011. Results:Of 320 enrolled patients, 227 (70.9%) reported diarrhea, and CDI testing was performed for 113 (49.8%) of the 227 patients. CDI testing was not recorded as being performed for the remaining 114 patients who reported having diarrhea. An additional 24 patients were tested for CDI but did not report having diarrhea. Seven (5.1%) of the 137 patients tested for CDI were positive. Conclusions:Testing for CDI is significantly lower than expected at diagnosis of IBD. Although the prevalence of CDI among tested patients is approximately 5%, a low testing rate suggests a significant quality issue in the diagnosis of IBD, with the potential for delayed diagnosis of CDI.

Opportunistic Screening for Bone Disease Using Abdominal CT Scans Obtained for other Reasons in Newly Diagnosed IBD Patients

Summary Bone disease is prevalent among patients with inflammatory bowel disease (IBD), though bone density screening remains underutilized. We used CT scans performed for other indications in IBD patients to identify and monitor osteopenia using CT attenuation values at the lumbar spine. Significant rates of bone disease were detected which would have otherwise gone undiagnosed.

Dietary behaviors in newly diagnosed youth with inflammatory bowel disease

ABSTRACT The impact of dietary behaviors on health outcomes in youth with inflammatory bowel disease (IBD) is unclear. The present study examined dietary behaviors and their association with biomedical factors in youth with IBD. Eighty-six newly diagnosed youth (mean age = 12.6) were included in analyses. Biomedical factors included disease activity and inflammatory markers. Despite adequate total caloric intake, estimated nutrient and fruit and vegetable intakes were below recommended levels. There was a significant negative association between vegetable intake and C-Reactive Protein (p = 0.04). Results suggest that dietary behaviors play an important role in IBD health outcomes.

P-025 Corticosteroid Use in A Prospective, Community-Based Cohort of Newly Diagnosed Inflammatory Bowel Disease Patients

BACKGROUND: Previous population-based studies report corticosteroid (CS) exposure rates that range from 39% to 75% within the first year of diagnosis with surgical resection rates as high as 13%–18% in the same timeframe.1–2 These reports represent an older cohort of patients enrolled over prolonged periods of time and do not necessarily reflect current treatment approaches. In this study, we examine CS use during the first year of IBD diagnosis in a novel, inception cohort. METHODS: Data were derived from the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), a prospective inception cohort of IBD patients who are residents of Rhode Island. Participants are enrolled within 12 months of diagnosis and complete follow-up assessments quarterly over the course of the first year. Participants who had been enrolled within 3 months from the date of diagnosis and had a confirmed diagnosis based on the NIDDK IBD Genetics Consortium criteria were included in current analyses. RESULTS: Table 1 outlines baseline clinical characteristics of patients included in our analyses (N = 272). Overall, 60% of Crohn’s disease (CD) and 57% of ulcerative colitis (UC) patients were exposed to at least one course of systemic CS during year 1.83% of patients treated with CS received their first course within 3 months of enrollment. Twenty-seven percent were exposed to topical steroid preparation (budesonide or rectal steroids) in year 1. Of the 66 patients with CD and 45 with UC not exposed to CS, 18 (27%) and 8 (18%) were treated with a topical steroid, respectively. Table 2 summarizes clinical outcomes. Five patients (2%) required a surgical resection in year 1.17% of all patients were treated with a biologic in year 1.26% of CD and 17% of UC patients exposed to systemic CS during year 1 were ultimately treated with a biologic. However, 17% of CD patients not exposed to CS during year 1 were treated with a biologic. All UC patients treated with a biologic were exposed to CS at some point during year 1. As of April 2013, 84 of the 272 (31%) patients included in our analyses had been treated with a biologic and 15 (6%) ultimately required a surgical resection. CONCLUSIONS: In this community-based cohort, 59% were exposed to at least one course of CS during their first year of enrollment. In contrast to previous studies, OSCCAR represents a more modern cohort of patients. While steroid exposure rates were similar or slightly higher than in previous reports, we observed a low rate of surgical resection. Future analysis will focus on how the effects of more contemporary treatments may have played a role in the low rates of surgery we observe.