Search

Background Fatigue is a disabling symptom in patients with inflammatory bowel disease (IBD). Its prevalence, mechanism, and impact remain poorly understood. We determined changes in fatigue status over time and identified predictors of incident or resolving fatigue. Methods This was a prospective study nested within the IBD Partners cohort. Participants prospectively completed the Multidimensional Fatigue Inventory and the Functional Assessment of Chronic Illness Therapy-Fatigue at baseline, 6 months, and 12 months. A Functional Assessment of Chronic Illness Therapy-Fatigue score ≤43 defined significant fatigue. Multivariable regression models using baseline covariates were used to identify risk factors for incident fatigue at 6 months and to predict the resolution of fatigue. Results A total of 2429 patients (1605 with Crohn disease, 824 with ulcerative colitis) completed a baseline assessment, and 1057 completed a second assessment at 6 months. Persistent fatigue (at baseline and at 6 months) was the most common pattern, affecting two-thirds (65.8%) of patients. One-sixth (15.7%) of patients had fatigue at 1 timepoint, whereas fewer than one-fifth (18.5%) of patients never reported fatigue. Among patients not fatigued at baseline, 26% developed fatigue at 6 months. The strongest predictor of incident fatigue was sleep disturbance at baseline (odds ratio, 2.91; 95% confidence interval, 1.48–5.72). In contrast, only 12.3% of those with fatigue at baseline had symptom resolution by month 6. Resolution was more likely in patients with a diagnosis of ulcerative colitis, quiescent disease, and an absence of significant psychological comorbidity. Conclusions Fatigue is common in patients with IBD. However, only a few fatigued patients experience symptom resolution at 6 or 12 months, suggesting the need for novel interventions to ameliorate its impact.

ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of full-length ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2 mRNA abundance and associated with APC tumor-suppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells. Significance: ECT2 overexpression and mislocalization support its role as a driver in colon cancer that is independent from its function in normal cell cytokinesis.

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA. Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis. Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02–7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11–2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45–1.08). Discussion/Conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC.

This article reviews epidemiological evidence of heritability and putative mechanisms in diverticular disease, with greatest attention to 3 recent studies of genetic associations with diverticular disease based on genome-wide or whole-genome sequencing studies in large patient cohorts. We provide an analysis of the biological plausibility of the significant associations with gene variants reported and highlight the relevance of ANO1, CPI-17 (aka PPP1R14A), COLQ6, COL6A1, CALCB or CALCA, COL6A1, ARHGAP15, and S100A10 to colonic neuromuscular function and tissue properties that may result in altered compliance and predispose to the development of diverticular disease. Such studies also identify candidate genes for future studies. Keywords: Diverticulum, Diverticulitis, Diverticular Hemorrhage

Background & Aims Increasing rates of young-onset colorectal cancer (CRC) have attracted substantial research and media attention, but we know little about racial disparities among younger adults with CRC. We examined racial disparities in young-onset CRC by comparing CRC incidence and relative survival among younger ( Methods Using data from the Surveillance, Epidemiology, and End Results program of cancer registries, we estimated CRC incidence rates (per 100,000 persons 20–49 years old) from 1992 through 2014 for different periods (1992–1996 vs 2010–2014) and races (white vs black). Relative survival was calculated as the ratio of observed survival to expected survival in a comparable cancer-free population. Results From 1992–1996 to 2010–2014, CRC incidence increased from 7.5 to 11.0 per 100,000 in white individuals and from 11.7 to 12.7 per 100,000 in black individuals. The increase in rectal cancer was larger in whites (from 2.7 to 4.5 per 100,000) than in blacks (from 3.4 to 4.0 per 100,000); in the 2010–2014 period, blacks and whites had similar rates of rectal cancer. Compared with whites, blacks had smaller increases in relative survival with proximal colon cancer but larger increases in survival with rectal cancer (from 55.3% to 70.8%). Conclusion In an analysis of the Surveillance, Epidemiology, and End Results database, we found racial disparities in incidence of young-onset CRC and patient survival for cancer of the colon but minimal difference for rectal cancer. Well-documented and recent increases in young-onset CRC have largely been due to increases in rectal cancer, especially in whites.

Pouchitis, the most common long-term complication after colectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), can lead to increased health care costs and diminished quality of life.1 In this study, we aimed to compare the total costs among patients diagnosed with pouchitis in the first 2 years after an IPAA with those among patients who were not diagnosed with pouchitis, using a large administrative claims database. Additionally, we aimed to investigate the specific drivers of cost among patients with an IPAA during the 2-year study period, including inpatient hospitalizations, emergency department visits, and pharmacy-related costs.

Background Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04). Conclusion In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.

Background & Aims Despite the increased numbers of older adults with inflammatory bowel diseases (IBDs), there are few studies regarding the safety and effectiveness of IBD treatments in older adults. The aim of this study was to compare the safety and effectiveness of anti–tumor necrosis factor (TNF)-α agents and vedolizumab in older adults with IBD. Methods We conducted a retrospective cohort study using an active comparator, new-user design for adults age 65 years and older with IBD initiating anti–TNF-α agents and vedolizumab in the Medicare claims database from 2014 to 2017. The primary safety outcome was infection-related hospitalization (excluding intra-abdominal and perianal abscesses). Co-primary outcomes to estimate effectiveness were IBD-related hospitalization, IBD-related surgery, and new corticosteroid use 60 days or more after biologic initiation. We performed propensity score weighting to control for confounding and estimated adjusted hazard ratios and 95% CIs using standardized morbidity ratio–weighted variables. Results We identified 1152 anti–TNF-α new users and 480 vedolizumab new users. The median age was 71 years in both cohorts and 11% were age 80 years or older. Crohn’s disease patients comprised 54% of the anti–TNF-α cohort and 57% of the vedolizumab cohort. There was no significant difference in demographics, health care utilization, or frailty in both cohorts. More than half of both cohorts had a Charlson comorbidity index of 2 or higher. Vedolizumab users had a decreased risk of infection-related hospitalization (adjusted hazard ratio, 0.47; 95% CI, 0.25–0.86). There was no significant difference in the outcomes approximating effectiveness. Conclusions Older IBD patients treated with vedolizumab had a lower risk of infection-related hospitalization compared with those initiating anti-TNFs. We observed no difference in effectiveness defined by hospitalizations, surgery, or new corticosteroid use.

Background & Aims This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. Methods Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC 50% among those with baseline FC >250 μg/g) and C-reactive protein (CRP) response (high-sensitivity CRP 50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). Results The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). Conclusions The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679

Background Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. Objective To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. Design Active-comparator, new-user, retrospective cohort studies. Setting Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants Immunocompetent adults with diverticulitis in the outpatient setting. Intervention Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. Measurements 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. Primary funding source National Institutes of Health.

BACKGROUND AND AIMS Anesthesia services for endoscopic procedures have proliferated with the promise of increased comfort and safety. Cirrhosis patients are higher risk for sedation, yet limited data are available describing anesthesia complications in this population. APPROACH AND RESULTS This cross-sectional study utilized the National Anesthesia Clinical Outcomes Registry, a multicenter quality-improvement database from 2010 to 2015. Patients with cirrhosis undergoing an endoscopy were identified by International Classification of Diseases, Ninth Revision (ICD-9)/Current Procedures Terminology (CPT) codes. The outcome of interest was serious anesthesia-related complication defined as cardiovascular, respiratory, neurological, drug related, patient injury, death, or unexpected admission. A mixed-effects multivariate logistic regression model determined odds ratios (ORs) between variables and serious complications, adjusting for potential confounders. In total, 9,007 endoscopic procedures were performed among patients with cirrhosis; 92% were esophagogastroduodenoscopies. The majority (81%) were American Society of Anesthesiologists (ASA) class ≥3, and 72% had a history of hepatic encephalopathy, ascites, varices, hepatorenal syndrome, or spontaneous bacterial peritonitis identified by ICD-9/CPT codes. In total, 87 complications were reported, 33 of which were serious. Frequency of serious complications was 0.4% or 378.6 per 100,000 procedures (95% confidence interval [CI], 260.8, 531.3). The majority of serious complications were cardiovascular (21 of 33), including 15 cardiac arrests. Serious complications were significantly associated with ASA 4/5 (OR, 3.84; 95% CI, 1.09, 13.57) and general anesthesia (OR, 4.71; 95% CI, 1.20, 18.50), adjusting for age, sex, ASA class, anesthesia type, inpatient status, portal hypertension history, and variable complication reporting practices. CONCLUSIONS Anesthesia complications among endoscopic procedures in cirrhosis are rare overall. Serious complications were predominantly cardiac and associated with sicker patients undergoing general anesthesia. The complexity of end-stage liver disease may warrant more intensive care during endoscopic procedures, including anesthesia monitoring.

Background Prior studies have identified racial disparities in the treatment and outcomes of inflammatory bowel disease (IBD). These disparities could be secondary to differences in biology, care delivery, or access to appropriate therapy. The primary aim of this study was to compare medication use among Medicaid-insured black and white patients with IBD, given uniform access to gastroenterologists and therapies. Methods We analyzed Medicaid Analytic eXtract data from 4 states (California, Georgia, North Carolina, and Texas) between 2006 and 2011. We compared the use of IBD-specific therapies, including analyses of postoperative therapy among patients with Crohn disease (CD). We performed bivariate analyses and multivariable logistic regression, adjusting for potential confounders. Results We identified 14,735 patients with IBD (4672 black [32%], 8277 with CD [58%]). In multivariable analysis, there was no significant difference in the odds of anti-tumor necrosis factor use by race for CD (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 0.99-1.28] or ulcerative colitis (aOR = 1.12; 95% CI, 0.96-1.32). Black patients with CD were more likely than white patients to receive combination therapy (aOR = 1.50; 95% CI, 1.15-1.96), and black patients were more likely than white patients to receive immunomodulator monotherapy after surgery for CD (31% vs 18%; P = 0.004). Conclusions In patients with Medicaid insurance, where access to IBD-specific therapy should be similar for all individuals, there was no significant disparity by race in the utilization of IBD-specific therapies. Disparities in IBD treatment discussed in prior literature seem to be driven by socioeconomic or other issues affecting access to care.

Although hemorrhoids are responsible for considerable economic cost and personal suffering, they have received surprisingly little research attention. In the United States, hemorrhoids are the third most common outpatient gastrointestinal diagnosis with nearly 4 million office and emergency department visits annually. The etiology of hemorrhoids is speculative. A low-fiber diet and constipation have historically been thought to increase the risk for hemorrhoids, but not proven. Symptoms commonly attributed to hemorrhoids include bleeding, pain, pruritus, fecal seepage, prolapse, and mucus discharge. Research has found that these symptoms were equally reported by patients with and without hemorrhoids. Medical therapies for hemorrhoids have not been formally studied except for fiber where the results have been inconsistent. A number of office-based interventions such as rubber band ligation and infrared coagulation are widely used and economically favorable for practitioners. Surgical procedures are effective at eliminating hemorrhoids but may be painful. Given the burden of disease and numerous gaps in our understanding, the time has come for targeted research to understand the cause, symptoms, and best treatment for patients with symptomatic hemorrhoids.

BACKGROUND & AIMS: Acute pouchitis is the most common non-surgical complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We used validated case-finding definitions for pouchitis to search administrative claims data and determine the incidence of pouchitis in the first 2 years after IPAA. METHODS: We identified all patients who underwent proctocolectomy with IPAA for UC in the IQVIA Legacy PharMetrics Adjudicated Claims Database, from January 1, 2007 through June 1, 2016. The primary outcome was the development of pouchitis within 2 years after IPAA. Secondary outcomes included isolated acute vs recurrent pouchitis, immunosuppressive therapy, further surgery, and admission to the hospital. RESULTS: Among 594 patients, the cumulative incidence of pouchitis within 2 years of IPAA was 48% (95% CI, 44%–52%). The cumulative incidence of isolated acute pouchitis was 29% (95% CI, 26%–33%). Compared to patients with isolated acute pouchitis, patients who received a diagnosis of recurrent pouchitis (cumulative incidence, 19%: 95% CI, 16%–22%) demonstrated increased outpatient visits, emergency department visits, and inpatient admissions (all P

Background High levels of patient activation (having the knowledge, skills, and confidence to effectively manage one’s care), have been associated with improved outcomes in many chronic conditions. There have been few studies of the effects of activation in patients with inflammatory bowel disease (IBD). We performed a large, prospective Internet-based study to assess the relationship between patient activation level and clinical remission in patients with Crohn’s disease or ulcerative colitis. Methods We administered the Patient Activation Measure (Insignia Health) to 1486 cohort participants. Patients completed a follow-up survey within 13 months (median, 189 days). We collected demographic and clinical data; anxiety and depression were assessed using Patient-Reported Outcomes Measurement Information System instruments. We used bivariate analyses and multivariable logistic regression to identify characteristics associated with low or high patient activation and to evaluate the association between levels of patient activation and subsequent disease activity. Results Higher anxiety (adjusted odds ratio [aOR], 0.32; 95% confidence interval [CI], 0.29–0.36) and depression (aOR, 0.33; 95% CI, 0.29–0.37) scores were associated with a decreased odds of high patient activation. After we adjusted for education status, smoking, medication use, and other confounders, we found that patients with high activation at baseline were more likely to be in clinical remission during the follow-up period (aOR, 1.71; 95% CI, 1.20–2.45). Conclusions In a large, prospective Internet-based cohort of patients with IBD, we found a strong association between patient activation and clinical remission. These findings suggest that patient activation affects disease outcomes.

Purpose To describe changes in symptom cluster membership over 1 year and to examine which demographic and clinical factors predict changes in symptom cluster membership among adults with inflammatory bowel disease. Design A retrospective longitudinal study of the Crohn's & Colitis Foundation of America Partners Cohort from 2012 to 2015. Methods We measured symptoms of pain interference, fatigue, sleep disturbance, depression, and anxiety. We used latent transition analysis to describe changes in symptom cluster membership (baseline, 6 months, and 12 months) and multinomial regressions to examine factors associated with symptom cluster membership transition. Findings Four groups were identified (N = 5,296): high symptom burden (32.3%-35.3%), low symptom burden (24.2%-27.1%), physical symptoms (19.0%-20.9%; pain, fatigue, sleep disturbance), and psychological symptoms (20.0%-21.5%; depression, anxiety). The probability of staying in the same group was .814 to .905. Moving from active disease into remission was associated with moving from the high burden to low burden and psychological symptom groups. Conclusions Symptom cluster membership was quite stable over 1 year. Research is needed to understand the underlying etiology of symptom clusters better and to develop interventions to reduce symptom burden in this vulnerable population. Clinical relevance Careful consideration of symptom management options should be done with patients to select options that are effective and potentially target multiple symptoms.

Aspects of sexual health, which can be adversely affected by chronic disease, have been inadequately explored in inflammatory bowel disease (IBD). We evaluated patient-reported interest in sexual activity and satisfaction with sex life in a large cohort of IBD patients. We conducted a cross-sectional study within the Crohn’s and Colitis Foundation Partners Internet cohort. Sequential participants completed a 6-question supplemental online survey to examine sexual interest and satisfaction using the Patient-Reported Outcome Measurement Information System® (PROMIS®) Sexual Function and Satisfaction measures. One-sample t tests were used to compare interest and satisfaction scores to general population norms. Among 2569 individuals, 1639 had Crohn’s disease (CD), 930 had ulcerative colitis (UC) or indeterminate colitis, and 71% were women. Mean PROMIS scores for sexual interest were comparable to the general US population in men (CD: 49 and UC: 48 vs. population mean 50) and women (CD: 41 and UC: 40 vs. population mean 42). However, sexual satisfaction scores were lower than the US population in men (CD: 48 and UC: 48 vs. 51) and women (CD: 47 and UC: 46 vs. 49), p

BACKGROUND: Many women with inflammatory bowel disease (IBD) report changes in symptoms in association with hormonal changes during menses, pregnancy, and hormonal contraceptive use, suggesting a hormonal influence on disease activity. We aimed to identify and characterize IBD symptom fluctuations in women during times of hormonal variation. METHODS: From June 2012 through September 2012, women enrolled in Crohn’s and Colitis Foundation of America Partners , an online Internet cohort of patients with IBD, were invited to participate in this study. Using a 5-point Likert scale, participants were asked to rate symptom changes during their menstrual cycle, pregnancy, the postpartum period, and after menopause. Clinical and demographic differences were assessed using univariate and multivariable methods. RESULTS: A total of 1,203 female patients with Crohn’s disease (CD) and ulcerative colitis (UC) participated (64% CD, 34% UC). Over half of the women with IBD reported worsening symptoms during menses. Symptom changes were similar between women with CD vs UC, except in pregnancy, where symptom worsening during pregnancy was more commonly seen in UC than CD (P = 0.02). Overall, women reporting symptom worsening were younger at the time of IBD diagnosis (P < 0.01), had lower quality of life (SIBDQ) scores (P < 0.01), and had a higher BMI (25 vs 24) than women without symptom worsening. CONCLUSIONS: Women with IBD report changes in symptom severity during times of hormone fluctuation. Further clarification of the role of hormones in IBD is warranted in order to understand these relationships and to identify potential management strategies for women with IBD and hormonally sensitive gastrointestinal symptoms.

OBJECTIVES Depression is prevalent in inflammatory bowel disease (IBD) patients. The impact of depression on IBD is not well-studied. It is unknown how providers should assess depression. METHODS We used data from the Sinai-Helmsley Alliance for Research Excellence cohort, to assess methods of diagnosing depression and effects of baseline depression on disease activity at follow-up. A patient health questionnaire (PHQ-8) score ≥5 was consistent with mild depression. Relapse was defined as a modified Harvey-Bradshaw Index ≥5 or Simple Clinical Colitis Activity Index >2. We performed binomial regression to calculate adjusted risk ratios (RRs). RESULTS We included 2,798 Crohn's disease (CD) patients with 22-month mean follow-up and 1,516 ulcerative colitis (UC) patients with 24-month mean follow-up. A total of 64% of CD patients and 45% of UC patients were in remission at baseline. By self-report, 20% of CD and 14% of UC patients were depressed. By PHQ-8, 38% of CD and 32% of UC patients were depressed (P

Background Metastases play a role in about 90% of cancer deaths. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells might provide diagnostic information about the likelihood that cancer cells have detached from the primary tumor. Used together with established diagnostic tests of detachment—lymph node evaluation and radiologic imaging—EMT marker measurements might improve the ability of clinicians to assess the patient’s risk of metastatic disease. Translation of EMT markers to clinical use has been hampered by a lack of valid analyses of clinically-informative parameters. Here, we demonstrate a rigorous approach to estimating the sensitivity, specificity, and prediction increment of an EMT marker to assess cancer cell detachment from primary tumors. Methods We illustrate the approach using immunohistochemical measurements of the EMT marker E-cadherin in a set of colorectal primary tumors from a population-based prospective cohort in North Carolina. Bayesian latent class analysis was used to estimate sensitivity and specificity in a setting of multiple imperfect diagnostic tests and no gold standard. Risk reclassification analysis was used to assess the extent to which addition of the marker to the panel of established diagnostic tests would improve mortality prediction. We explored how changing the latent class conditional dependence assumptions and definition of marker positivity would impact the results. Results All diagnostic accuracy and prediction increment statistics varied with the choice of cut point to define marker positivity. When comparing different definitions of marker positivity to each other, numerous trade-offs were observed in terms of sensitivity, specificity, predictive discrimination, and prediction model calibration. We then discussed several implementation considerations and the plausibility of analytic assumptions. Conclusions The approaches presented here can be extended to any EMT marker, to most forms of cancer, and to different kinds of EMT marker measurements, such as RNA or gene methylation data. These methods provide valid, clinically-informative assessment of whether and how to use a given EMT marker to refine tumor staging and consequent treatment decisions. Electronic supplementary material The online version of this article (10.1186/s12885-017-3964-3) contains supplementary material, which is available to authorized users.

Symptoms (pain, fatigue, sleep disturbance, depression, and anxiety) in inflammatory bowel disease (IBD) are associated with reduced quality of life. Understanding how IBD symptoms cluster and the clinical and demographic factors associated with symptom clusters will enable focused development of symptom management interventions. The study purposes were to (i) identify symptom cluster membership among adults with IBD and (ii) examine associations between demographic (age, gender, race/ethnicity, and education) and clinical factors (smoking status, time since diagnosis, medication type, IBD type, disease activity), and membership in specific symptom cluster groups. We conducted a retrospective study of data from the Crohn's and Colitis Foundation of America's (CCFA) Partners Cohort and used Patient Reported Outcome Measurement Information System (PROMIS) measures to measure pain interference, fatigue, sleep disturbance, anxiety, and depression. The sample included 5,296 participants with IBD (mean age 44, 72% female). In latent class analysis (LCA), four groups of participants were identified based on symptoms: "low symptom burden" (26% of sample), "high symptom burden" (38%), "physical symptoms" (22%), and "psychological symptoms" (14%). In multinomial regression, female gender, smoking, corticosteroids, Crohn's disease, and active disease state were associated with membership in the high symptom burden group. Additional research is needed to test interventions that may be effective at reducing symptom burden for individuals with IBD.

BACKGROUND Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the standard surgical treatment for the majority of patients with inflammatory bowel disease (IBD) who require colectomy. We evaluated the prevalence of pouch-related symptoms among the Crohn's and Colitis Foundation of America Partners cohort and the effect of pouch-related symptoms on Patient-Reported Outcome Measurement Information System measures. METHODS We performed analyses nested in the Crohn's and Colitis Foundation of America Partners cohort. We used bivariate analyses to compare demographics and medication use among patients with ulcerative colitis or indeterminate colitis and pouch-related symptoms and those with IPAA without symptoms. We also compared Patient-Reported Outcome Measurement Information System domains (measured in T-scores) and short IBD questionnaire quality of life scales between symptomatic pouch patients (over the past 6 mo) and those without symptoms. RESULTS Among 243 patients reporting a history of IPAA, 199 (82%) reported a history of pouch symptoms. Patients with recent pouch symptoms demonstrated higher mean T-scores in pain interference (53.0 versus 45.3; P < 0.001), depression (51.0 versus 46.4; P = 0.002), and fatigue (56.3 versus 47.0; P < 0.001). Symptomatic pouch patients reported lower mean scores in social role satisfaction (47.4 versus 54.6) and short IBD questionnaire (4.8 versus 5.8) (both P < 0.001). These differences were all clinically meaningful. CONCLUSIONS In a large sample of patients with IBD, nearly all patients with IPAA reported a history of pouch symptoms. Patients experiencing symptoms within the 6 months before the survey assessment demonstrated clinically meaningful decrements in patient-reported outcomes in multiple domains of physical and psychosocial functioning.

Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4 ) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas. In the parent study, 1121 participants with a recent adenoma were randomized to study agents to be taken until the next surveillance colonoscopy about 3 years later. In this pilot study, LXA4 and RvD1 from samples taken near the end of study treatment were measured in a randomly selected sub-set of 200 participants. Commercially available ELISA kits to assay the analytes were validated using a metabololipidomic LC-MS/MS assay. Poisson regression with a robust error variance was used to calculate risk ratios and 95% confidence intervals. Plasma LXA4 and RvD1 were not associated with the risk of adenoma occurrence. LXA4 at the end of study follow-up was 32% (P = 0.01) proportionately higher in women compared to men. A similar non-significant trend toward higher levels among women was observed for RvD1. Our preliminary findings provided no evidence that plasma LXA4 or RvD1 are associated with reduced risk of colorectal adenoma occurrence, but suggest LXA4 may differ among men and women. Future studies focusing on SPM's local effects and levels in the colon are needed.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.

Background There is a growing interest in the role of gut bacteria in a number of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently, fecal microbiota transplantation (FMT) is utilized for the treatment of Clostridium difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for the treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an Internet-based cohort. Methods Patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on the use of FMT between January 2017 to September 2018 (n = 5430). A cross-sectional analysis was performed within patients who completed the survey and did not have a pouch or ostomy. Patients’ demographic characteristics, disease activity and phenotype, mode of FMT delivery, and patient-reported efficacy were compared. Results Among 3274 eligible patients, 51 (1.6%) responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had ulcerative colitis/indeterminate colitis (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient-reported efficacy was lower for FMT given for a non-C. difficile indication. Conclusions Patients undergoing FMT for an indication other than C. difficile infection were more likely to have ulcerative colitis, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of proven benefit associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite., Lay Summary In a survey-based study of 3247 patients with inflammatory bowel disease, 51 reported having a fecal transplant in the past. Patients were more likely to self-administer the transplant and reported lower response rates if done for an indication other than C. difficile.

Background Improved treatment approaches for ulcerative colitis (UC), including novel medications, might reduce the need for colectomy. We performed a retrospective cohort study of adult patients (age 18–64) with UC in the United States to examine time trends for colectomy and biologic use from 2007 to 2016. Methods We estimated quarterly rates for colectomy and biologic use using the IQVIA Legacy PharMetrics Adjudicated Claims Database. We used interrupted time series methods with segmented regression to assess time trends with 95% confidence intervals (CIs) for biologic use and colectomy before and after the emergence of newly available biologic therapies in 2014. Results Among 93,930 patients with UC, 2275 (2.4%) underwent colectomy from 2007 to 2016. Biologic use rates increased significantly from 2007 to 2016, from 131 per 1000 person-years in 2007 (95% CI, 121 to 140) to 589 per 1000 person-years in 2016 (95% CI, 575 to 604; P < 0.001). Colectomy rates decreased significantly between 2007 and 2016, from 7.8 per 1000 person-years (95% CI, 7.4 to 8.2) to 4.2 per 1000 person-years in 2016 (95% CI, 3.2 to 5.1; P < 0.001). An interruption in 2014 was associated with a positive trend deflection for biologic use (+72 treatments per 1000 person-years per year (95% CI, 61 to 83) and a negative trend deflection for colectomy (–0.76 per 1000 person-years per year; 95% CI, –1.47 to –0.05). Conclusions Among commercially insured patients in the United States from 2007 to 2016, biologic use rates increased, colectomy rates decreased, and both trends were impacted by the interruption in 2014. These findings suggest that new biologic therapies may have contributed to decreased colectomy rates.

Background & Aims The prevalence of diverticulosis differs with demographic features of patients, but evidence is limited. Well-defined demographic studies are necessary to understand diverticulosis biology. We estimated the prevalence of diverticulosis among patients of different ages, sexes, and races and ethnicities and calculated odds ratios. Design Using data from an endoscopic database, we identified 271,181 colonoscopy procedures performed from 2000 through 2012 at 107 sites in the United States. Our analysis included individuals 40 years and older who underwent colonoscopy examination for average-risk screening. The outcome was any reported diverticulosis on colonoscopy. Multivariate analyses were performed using logistic regression to estimate odds ratios (ORs) and 95% CI values, adjusting for confounding variables. Results The prevalence of diverticulosis increased with age in men and women of all races and ethnicities. Women 40-49 years old had significantly lower odds of any diverticulosis (OR, 0.71; 95% CI, 0.63-0.80) compared with men 40-49 years old, after adjustment. The strength of this association decreased with age. Compared with non-Hispanic white individuals, non-Hispanic black individuals (OR, 0.80; 95% CI, 0.77-0.83) and Asian/Pacific Islanders (OR, 0.38; 95% CI, 0.35-0.41) had lower odds of any diverticulosis. However, non-Hispanic black individuals (OR, 1.53, 95% CI, 1.44-1.62) had increased odds of any proximal diverticulosis, whereas Asian/Pacific Islanders (OR, 3.12; 95% CI, 2.67-3.66) had increased odds of only proximal diverticulosis. Conclusions In an analysis of data from 271,181 colonoscopy procedures, diverticulosis was less prevalent in women compared with men in the same age groups, indicating that sex hormones might affect pathogenesis. Differences in the odds of diverticulosis by race and ethnicity indicate a genetic contribution to risk.

BACKGROUND. Although hemorrhoids are a common indication for seeking health care, there are no contemporary estimates of burden and cost. We examined data from an administrative claims database to estimate health care use and aggregate costs. METHODS. We conducted a cross-sectional study using the MarketScan(®) Commercial Claims and Encounters Database for 2014. The analysis included 18.9 million individuals who were aged 18-64 and continuously enrolled with prescription coverage. Outpatient hemorrhoid claims were captured using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes in the first position, as well as Common Procedural Terminology codes. Prescription medications were identified using National Drug Codes. Annual prevalence and costs were determined by summing gross payments for prescription medications, physician encounters and facility costs. We used validated weights to standardize annual cost estimates to the US employer-insured population. RESULTS. In 2014, we identified 227,638 individuals with at least one outpatient hemorrhoid-related claim (annual prevalence, 1.2%). Among those, 119,120 had prescription medication claims, 136,125 had physician claims and 28,663 had facility claims. After standardizing, we estimated that 1.4 million individuals in the US employer-insured population sought care for hemorrhoids in 2014 for a total annual cost of $770 million. This included $322 million in physician claims, $361 million in outpatient facility claims and $88 million in prescription medication claims. CONCLUSIONS. The estimated economic burden of hemorrhoids in the employer-insured population approaches $800 million annually. Given the substantial and rising burden and cost, expanded research attention should be directed to hemorrhoidal etiology, prevention, and treatment.

There is increased interest in measuring patient-reported outcomes (PROs) such as quality of life (QoL) among patients with inflammatory bowel disease (IBD). We aimed to create and validate a new measure of QoL to assess the psychosocial burden of IBD using publicly available assessment tools.Using the Crohn'sColitis Foundation's IBD Partners cohort, we performed several cross-sectional and longitudinal analyses to create a new PRO-based evaluation (PROBE) of QoL among patients with Crohn's disease (CD) and ulcerative colitis (UC). We used factor analysis and Pearson correlation test to identify candidate questions for inclusion, Wilcoxon rank-sum test to examine responsiveness of the PROBE to changes in disease activity, and test-retest reliability assessments in patients with stable disease activity. We also compared the PROBE to the Short Inflammatory Bowel Disease Questionnaire to assess construct validity.A total of 4,854 patients (64% CD, 36% UC) completed surveys with 6 items included in the final PROBE. Compared with baseline there was a significant decrease in PROBE scores at follow-up among patients who experienced a flare for UC (25.0 vs 22.2, P = 0.001) and CD (23.1 vs 21.0, P0.001). Among patients with stable disease activity, Cronbach alpha was 0.87 in CD and 0.82 in UC. The PROBE correlated well with the Short Inflammatory Bowel Disease Questionnaire in CD (r = 0.88) and UC (r = 0.86).We created a novel measure to assess QoL in patients with IBD using publicly available survey items. This new PROBE can be used to facilitate clinical care, clinical and epidemiological research, and quality improvement.

Objective Therapeutic diets have been used to treat symptomatic Crohn's disease (CD). The Specific Carbohydrate Diet (SCD) and Mediterranean Diet (MD) have been associated with reduced CD symptoms. This study compared the effectiveness of these two diets for mild to moderate CD symptoms. Methods The Diet to INducE Remission in Crohn's Disease (DINE CD) study was a multicenter randomized comparative effectiveness trial of SCD vs MD. The study included adult patients with CD and with mild-moderate symptoms defined as a short Crohn's Disease Activity Index (sCDAI) score 176-399. Patients were randomly assigned 1:1, stratified by use of biologic medications, to consume either the SCD or MD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks compliant with their assigned diet. After 6 weeks, participants could purchase some or all of their food while following the diet on their own. The primary outcome was symptomatic remission (sCDAI 50% from baseline among those with baseline FC >250 μg/g), C Reactive Protein (CRP) response (high-sensitivity CRP (hsCRP) 50% reduction from baseline among those with hsCRP >5mg/L), short IBDQ and PROMIS measures of fatigue, pain, sleep and social isolation. Comparisons between groups used Cochrane-Mantel-Haenszel chi2 or t-test and within groups used paired t-test. Results 194 patients were randomized, but due to an error, 3 participants had a baseline sCDAI 0.2 for all comparisons). The percentage of participants who achieved symptomatic remission at week 6 did not differ by diet (43.5% with MD and 46.5% with SCD; p=0.77) (Figure). Clinical remission was achieved in 47.8% with MD and 48.5% with SCD (p=0.93). FC response was achieved in 4 participants (30.8%) with MD and 8 participants (34.8%) with SCD (p=0.83). CRP response was achieved in only 1 participant (3.6%) with MD and 2 participants (5.4%) with SCD (p=0.68). There was no evidence of heterogeneity of response based on presence or absence of confirmed inflammation at screening (Figure; test for interaction P=0.68). Conclusions Symptomatic remission was achieved in ≥40% with both diets regardless of confirmed inflammation. CRP response was uncommon. None of the effectiveness measures were significantly different by treatment group. Download : Download high-res image (86KB) Download : Download full-size image Table 1 . Change in symptoms from screening to week 6 by treatment arm Download : Download high-res image (73KB) Download : Download full-size image Figure 1 . Comparative effectiveness of Specific Carbohydrate Diet and Mediterranean Diet

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4-6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis.

BACKGROUND Inflammatory bowel disease (IBD) patients with persistent symptoms despite no or minimal inflammation are frequently described as having an overlap of IBD and irritable bowel syndrome (IBD-IBS). Limited data are available on how IBS impacts the individual patient with IBD. In this study, we aimed to evaluate the prevalence of IBD-IBS and investigate its impact on patient-reported outcomes. METHOD We performed a cross-sectional analysis within the CCFA Partners Study. Bivariate analyses and logistic regression models were used to investigate associations between IBD-IBS and various demographic, disease factors, and patient-reported outcomes including anxiety, depression, sleep disturbances, pain interference, and social satisfaction. RESULTS Of the 6309 participants included, a total of 1279 (20%) reported a coexisting IBS diagnosis. The prevalence of IBD-IBS in this cohort was similar within disease subtypes. A diagnosis of IBD-IBS was associated with higher narcotic use compared with those with no IBS diagnosis for both Crohn's disease, 17% versus 11% (P < 0.001) and ulcerative colitis/indeterminate colitis, 9% versus 5% (P < 0.001). Quality of life, as measured by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was lower in patients with IBD-IBS compared with those without. IBD-IBS diagnosis was associated with anxiety, depression, fatigue, sleep disturbances, pain interference, and decreased social satisfaction. CONCLUSIONS In this sample of patients with IBD, high prevalence of concomitant IBS diagnosis was observed. IBD-IBS diagnosis was associated with increased narcotic use and adverse patient-reported outcome. Appropriate diagnosis, treatment, and counseling may help improve the functional status of IBD-IBS patients and decrease narcotic use.

Background: Inflammatory bowel disease (IBD) is increasing in Asians. We sought to better understand differences in IBD between Asians and whites in the United States (US). Methods: We used data from the Sinai-Helmsley Alliance for Research Excellence cohort to assess disease characteristics for US-born Asians, Asian immigrants, and whites. We used bivariate analyses to describe clinical characteristics by race. We used logistic regression to determine baseline odds of immunosuppression and binomial regression to estimate risk ratios for worsening disease at follow-up. Results: We included 5,223 whites, 35 US-born Asians, and 81 Asian immigrants. Crohn disease (CD) was present in 64% of whites, 40% of US-born Asians, and 51% of Asian immigrants. At baseline, 58% of whites, 62% of US-born Asians, and 67% of Asian immigrants were in remission by disease activity index score (p = 0.238). There were no significant differences in CD location and behavior or ulcerative colitis extent. Asians had significantly more perianal disease than whites (33 vs. 18%, p = 0.007). Asians were more likely to have ocular manifestations than whites (3.4 vs. 0.7%, p = 0.022). Asians were also significantly less likely to be depressed than whites (25 vs. 35%, p = 0.022). Adjusting for confounders, Asians had half the odds of being treated with biologics compared with whites (OR: 0.45, 95% CI: 0.30-0.67). Adjusting for disease behavior and remission status, there were no differences in IBD-related surgery or hospitalization, new biologic or steroid prescription, or relapse rates between Asians and whites at follow-up. Conclusion: Asians are more likely to have perianal disease and ocular extraintestinal manifestations. After controlling for confounders, Asians were less likely to be treated with biologic agents. Despite this, there were no significant differences in outcomes over time between Asians and whites. Differences in disease phenotypes in Asians may reflect differences in genetics.

BACKGROUND As variation in care has previously been linked to quality, we aimed to describe variations in inflammatory bowel diseases care by gastroenterology (GI) practice setting. METHODS We performed a cross-sectional study within the Crohn's and Colitis Foundation of America Partners and used bivariate analyses to compare patient characteristics by GI practice setting (GI-academic [GIA], GI-private, or GI-other). Regression models were used to describe the effects of provider type on steroid use, disease activity, and the quality of life. RESULTS The study included 12,083 patients with inflammatory bowel diseases (7576 with Crohn's disease [CD] and 4507 with ulcerative colitis [UC]). Nearly 95% reported visiting a GI provider annually. Also, CD patients seen by GIA were younger, better educated, used less 5-aminosalicylate agents, and had higher biologic and immunomodulator use (P < 0.001 for all). On multivariate analysis of CD patients, GIA used less steroids when compared with GI-private (odds ratio, 0.84; 95% confidence interval, 0.67-1.06) or GI-other (odds ratio, 0.66; 95% confidence interval, 0.49-0.89). GIA patients were more likely to be in remission, have flu vaccine, and have better quality of life. UC patients seen by GIA were younger, had more hospitalizations, and previous surgery (P < 0.001 for all). No differences existed for steroid use, remission, flu vaccine, or quality of life for UC care on bivariate or multivariate analyses. CONCLUSIONS Significant variations in care patterns and quality measures exist for CD across GI provider types, without similar variation in UC care. Interventions to reduce variations in care could improve the quality of care in CD.

Background & Aims Chronic inflammatory bowel diseases (IBDs) have been associated with an abnormal mucosal response to the gastrointestinal microbiota. Although dietary fiber affects the gastrointestinal microbiota, there is limited information on the role of fiber on IBD activity. We investigated factors associated with fiber consumption and whether it was associated with flares in patients with IBD. Methods We collected a completed 26-item dietary survey from 1619 participants in the Crohn's and Colitis Foundation of America Partners Internet cohort (Crohn's disease, 1130; ulcerative colitis/indeterminate colitis, 489). Eligible individuals were in remission based on disease activity index at baseline and completed a follow-up survey 6 months later. Fiber and whole grain consumption were categorized into quartiles and deciles. Disease flare at 6 months was defined as a disease activity index score exceeding remission cutoff values, and/or an IBD-related surgical procedure or hospitalization since baseline. Results Participants with longer duration of disease, past history of surgery, and past IBD hospitalization ate less fiber. The risks for disease flare differed by disease type. Compared with those in the lowest quartile of fiber consumption, participants with Crohn's disease in the highest quartile were less likely to have a flare (adjusted odds ratios [OR], 0.58; 95% confidence interval [CI], 0.37–0.90). Participants with Crohn's disease who reported that they did not avoid high-fiber foods were ∼40% less likely to have a disease flare than those who avoided high-fiber foods (adjusted OR, 0.59; 95% CI, 0.43–0.81). There was no association between fiber intake and flares in patients with ulcerative colitis (adjusted OR, 1.82; 95% CI, 0.92–3.60). Conclusions Intake of dietary fiber is associated with reduced disease flares in patients with Crohn's disease, but not UC. Recommendations to limit dietary fiber should be re-evaluated.

BACKGROUND Older individuals with inflammatory bowel disease (IBD) require ongoing medications. We aimed to describe (1) medication use in older and younger IBD patients and (2) medication associations with patient reported outcomes (PROs) in older patients. METHODS We conducted cross-sectional and longitudinal analyses within CCFA Partners internet-based cohort of patients with self-reported IBD. We assessed medication use by disease sub-type and age. We used bivariate analyses to (1) compare medication use in older and younger patients and (2) determine associations between continued steroid use and patient reported outcomes in older patients. RESULTS We included 5382 participants with IBD; 1004 were older (≥age 60). Older patients with Crohn's disease (CD) had lower antitumor necrosis factor alpha (anti-TNF) use at baseline (29.1% versus 44.3%, P < 0.001), comparable steroid use (16.0% versus 16.5%, P = 0.77), and higher aminosalicylate use (40.3% versus 33.9%, P = 0.003) versus younger patients. Older ulcerative colitis (UC) patients had similar anti-TNF use (16.0% versus 19.2%, P = 0.16), lower steroid use (9.6% versus 15.4%, P = 0.004), and higher aminosalicylate use (73.8% versus 68.2%, P = 0.04) at baseline. In longitudinal analyses, older CD patients had higher continued steroid use (11.6% versus 7.8%, P = 0.002); which was associated with worsened anxiety (P = 0.02), sleep (P = 0.01), and fatigue (P = 0.001) versus nonuse. Older CD patients on steroids, versus anti-TNF or immunomodulators, had increased depression (P = 0.04) and anxiety (P = 0.03). CONCLUSIONS Medication utilization differs in older patients with IBD. Older CD patients have higher continued steroid use associated with worsened patient reported outcomes. As in younger IBD populations, continued steroid use should be limited in older patients.

The prevalence of depression is high in patients with Crohn’s Disease (CD). We examined the influence of affective-cognitive symptoms of depression on the risk of exacerbation of CD.

BackgroundStudies suggest that there is a temporal relationship between depression and Crohn’s disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression–CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective–cognitive dimension of depression.MethodsWe studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective–cognitive index of depression. Crohn’s disease status and the affective–cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data.ResultsThe results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective–cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse.ConclusionsThe hypothesis that an affective–cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.

OBJECTIVE A recent study raises concerns that dipeptidyl peptidase 4 inhibitors (DPP4i) are associated with increased risk of inflammatory bowel disease (IBD). We evaluated the association between new use of DPP4i and IBD risk compared with other second-line antihyperglycemics. RESEARCH DESIGN AND METHODS We implemented an active-comparator, new-user cohort design using two U.S. administrative claims databases for commercially insured (MarketScan) and older adult (Medicare fee-for-service, 20% random sample) patients from January 2007 to December 2016. We identified patients, aged ≥18 years, who initiated DPP4i versus sulfonylureas (SUs) or initiated DPP4i versus thiazolidinediones (TZDs) and were without prior diagnosis, treatment, or procedure for IBD. The primary outcome was incident IBD, defined by IBD diagnosis preceded by colonoscopy and biopsy and followed by IBD treatment. We performed propensity score weighting to control for measured baseline confounding, estimated adjusted hazard ratios (aHRs [95% CI]) using weighted Cox proportional hazards models, and used random-effects meta-analysis models to pool aHRs across cohorts. RESULTS We identified 895,747 eligible patients initiating DPP4i, SU, or TZD; IBD incidence rates ranged from 11.6 to 32.3/100,000 person-years. Over a median treatment duration of 1.09–1.69 years, DPP4i were not associated with increased IBD risk across comparisons. The pooled aHRs for IBD were 0.82 (95% CI 0.41–1.61) when comparing DPP4i (n = 161,612) to SU (n = 310,550) and 0.76 (0.46–1.26) when comparing DPP4i (n = 205,570) to TZD (n = 87,543). CONCLUSIONS Our population-based cohort study of U.S. adults with diabetes suggests that short-term DPP4i treatment does not increase IBD risk.

Background Fatigue is a commonly reported and sometimes disabling symptom in patients with inflammatory bowel disease (IBD). Its prevalence, mechanism, and impact remain poorly understood. Using a large cohort of patients with IBD, we aimed to prospectively determine the trajectory of fatigue and to identify determinants and impact of incident and prevalent fatigue on patients with IBD. Methods This prospective study was nested within the IBD partners cohort, a validated internet-based cohort of patients with IBD. Participants were invited to prospectively complete questionnaires assessing fatigue status at baseline and subsequently after 6 and 12 months. Fatigue was assessed using the validated Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score. A FACIT-F score of < 43 was defined as significant fatigue. We examined the trajectory and predictors of different courses of fatigue including incident fatigue (not fatigued as baseline but fatigued at 6 months) and resolved fatigue (fatigue at baseline but resolved on follow-up). Results A total of 2429 patients (1605 CD, 824 UC) completed baseline assessment among whom 1057 completed a second assessment at 6 months. First, we identified three distinct patterns of fatigue. Episodic fatigue defined as fatigue at any one (but not both) time point was the most common, affecting 1182 patients (57.0%). Persistent fatigue (at both baseline and follow-up) affected 33.5% (n = 695) while only 196 patients (9.5%) reported no fatigue at any time point (n = 196) (Figure). Patients that reported persistent or intermittent fatigue were more likely to have active disease (p < 0.001), be younger, (p < 0.001), report anaemia (p = 0.002) and low vitamin B12 levels (p < 0.001) and to have a prior diagnosis of depression, anxiety or sleep disorder (p < 0.001). Among patients who were not fatigued at baseline, 26% developed new fatigue at 6 months defined as incident fatigue). The strongest predictor of this being presence of sleep disturbance at baseline (OR 2.45, 95% CI 0.24–1.55) (Table). In contrast, only 12.3% of those with fatigue at baseline had symptom resolution by month 6. Resolution of fatigue was more common in those with UC (p = 0.03), quiescent disease at baseline (p = 0.006), not receiving biologic therapy at baseline (p = 0.016) and no sleep disturbance (p < 0.001), anxiety (p = 0.002) and depressive (p = 0.005) symptoms at baseline. Conclusion Our findings indicate three distinct trajectories of fatigue in patients with IBD with their distinct predictors. Importantly, 26% of patients developed new onset fatigue at 6 months demonstrating the substantial impact of this on patients with IBD.

Background & Aims Patients with Crohn’s disease (CD) must make decisions about their treatment. We aimed to quantify patients’ preferences for different treatment outcomes and adverse events. We also evaluated the effects of latent class heterogeneity on these preferences. Methods An online stated-preference survey was completed by 812 individuals with CD in the Crohn’s and Colitis Foundation Partners cohort (IBD Partners). Patients were given information on symptoms and severity of active disease; duration of therapy with corticosteroids; and risks of serious infection, cancer and surgery. Patients were asked to assume that their treatment was not working and to choose an alternative therapy. The primary outcome was remission-time equivalents (RTE) of a given duration of symptom severity or treatment-related risk. Latent class choice models identified groups of patients with dominant treatment-outcome preferences and associated patient characteristics with these groups. Results Latent class analysis demonstrated 3 distinct groups of survey responders whose choices were strongly influenced by avoidance of active symptoms (61%), avoidance of corticosteroid use (25%), or avoidance of risks of cancer, infection or surgery (14%) when choosing a therapy. Class membership was correlated with age, sex, mean short CD activity index score and corticosteroid avoidance. RTEs in each latent class differed significantly from the mean RTEs for the overall sample, although the symptom-avoidant class most closely approximated the overall sample. Conclusions In an online survey of patients with CD, we found substantial heterogeneity in preference for medication efficacy and risk of harm. Physicians and regulators should therefore not assume that all patients have mean-value preferences—this could result in significant differences in health-technology assessment models.

Differences in tumor characteristics might partially account for mortality disparities between African American (AA) and European American (EA) colorectal cancer patients. We evaluated effect modification by race for exposure and patient-outcomes associations with colorectal tumor methylation among 218 AA and 267 EA colorectal cancer cases from the population-based North Carolina Colon Cancer Study. Tumor methylation was assessed in CACNA1G, MLH1, NEUROG1, RUNX3, and SOCS1. We used logistic regression to assess whether associations between several lifestyle factors—intake of fruits, vegetables, folate, and non-steroidal anti-inflammatory drugs—and tumor methylation were modified by race. Proportional hazards models were used to evaluate whether race modified associations between tumor methylation and time to all-cause mortality. Greater fruit consumption was associated with greater odds of high NEUROG1 methylation among EA at methylation cut points of 15–35% (maximum OR 3.44, 95% CI 1.66, 7.13) but not among AA. Higher folate intake was associated with lower odds of high CACNA1G methylation among EAs but not AAs. Tumor methylation was not associated with all-cause mortality for either group. Race might modify associations between lifestyle factors and colorectal tumor methylation, but in this sample did not appear to modify associations between tumor methylation and all-cause mortality.