Orangutans and the evolution of sharp stone tools.

Orangutans use stone tools in a variety of modes, including cutting. This behavior appears to be learned from trusted social partners.

Orangutan strategies for solving a visuospatial memory task.

The popular game known as Concentration (also commonly referred to as Memory), in which players search for matching pairs among a grid of face-down cards, provides a robust platform for examining visuospatial memory in a simple and nonverbal way. Five orangutans (Pongo ssp.) at the Indianapolis Zoo were given a modified version of the Concentration Game in which three cards were shown face-down on a computer screen, two of which matched each other while the third was a foil. Subjects overturned two cards at a time by touching them, with trials terminating in a food reward if the overturned cards matched, or reverting to their face-down position if they did not. A constraint was experimentally imposed on the game whereby the first two cards touched would never match, resulting in an optimal strategy composed of touching the first two cards, followed by the third, followed by the card among the first two cards that matched the third. We aimed to measure the extent to which orangutans would memorize and utilize visuospatial cues to solve the task in the optimal manner. Findings showed that three of five subjects utilized an optimal strategy more often than would be expected by chance, but also over utilized specific patterns of choices instead of adjusting their strategies to minimize the overall number of card flips. Visuospatial recall played a role in several of the participants' strategies for completing the task, but not to an extent that was necessary to achieve optimal gameplay.

Complications of Anesthesia Services in Gastrointestinal Endoscopic Procedures.

BACKGROUND & AIMS: Despite the increased use of anesthesia services for endoscopic procedures in the United States, the risks of anesthesia-directed sedation (ADS) are unclear. We analyzed national data from multiple centers to determine patterns of use of anesthesia services and risk factors for serious complications. METHODS: We performed a cross-sectional study using the National Anesthesia Clinical Outcomes Registry, a national quality improvement database. Univariable and bivariate analyses investigated frequencies and relationships between predefined variables and serious complications of anesthesia (cardiovascular, respiratory, neurologic, drug-related, patient injury, death, or unexpected admission). A multivariable mixed-effects model determined the odds ratios between these variables and serious complications, adjusting for confounders and varying reporting practices. RESULTS: In total, 428,947 endoscopic procedures of adults were performed using ADS from 2010 to 2015. The population was 54.9% female with a mean age of 59.1 years, and predominantly American Society of Anesthesiologists classes 2 and 3 (74.4%). More than half of the procedures were colonoscopies (51.4%); 37.4% were esophagogastroduodenoscopies and 6.5% were endoscopic retrograde cholangiopancreatographies. A total of 4441 complications (1.09%) were reported; 1349 were serious complications (0.34%). In multivariable analysis, older age, American Society of Anesthesiologists classes 4 and 5, esophagogastroduodenoscopy, general anesthesia, cases performed on an overnight shift, and longer cases were associated independently and significantly with serious complications. CONCLUSIONS: In an analysis of data from the National Anesthesia Clinical Outcomes Registry, we found ADS during endoscopy to be safe, with few serious complications (<1% of procedures). Risk of ADS complications increased with older age, more severe disease, procedure type, and case complexity.

Efficacy of Budesonide vs Fluticasone for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial.

BACKGROUND AND AIMS: Topical steroid treatments for eosinophilic esophagitis (EoE) include swallowed fluticasone from a multi-dose inhaler (MDI) or oral viscous budesonide (OVB) slurry, but the 2 have never been compared. We assessed whether OVB was more effective than MDI for initial treatment of patients with EoE. METHODS: In a double-blind, double-dummy trial, patients with a new diagnosis of EoE were randomly assigned to groups given 8 weeks of either OVB (1 mg/4 mL) twice daily plus a placebo inhaler (n = 56) or fluticasone MDI (880 µg) twice daily plus a placebo slurry (n = 55). Primary outcomes were post-treatment maximum eosinophil counts per high-power field (eos/hpf) and a validated dysphagia score (dysphagia symptom questionnaire [DSQ]) at week 8. Secondary outcomes included endoscopic severity (validated EoE endoscopic reference score), histologic response (<15 eos/hpf), and safety. RESULTS: In a modified intention-to-treat analysis, the subjects had baseline peak eosinophil counts of 73 and 77 eos/hpf in the OVB and MDI groups, respectively, and DSQ scores of 11 and 8. Post-treatment eosinophil counts were 15 and 21 in the OVB and MDI groups, respectively (P = .31), with 71% and 64% achieving histologic response (P = .38). DSQ scores were 5 and 4 in the OVB and MDI groups (P = .70). Similar trends were noted for post-treatment total EoE endoscopic reference scores (2 vs 3; P = .06). Esophageal candidiasis developed in 12% of patients receiving OVB and 16% receiving MDI; oral thrush was observed in 3% and 2%, respectively. CONCLUSIONS: In a randomized clinical trial, initial treatment of EoE with either OVB or fluticasone MDI produced a significant decrease in esophageal eosinophil counts and improved dysphagia and endoscopic features. However, OVB was not superior to MDI, so either is an acceptable treatment for EoE. ClinicalTrials.gov ID NCT02019758.

Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development.

BACKGROUND & AIMS: Exposure to biologic and immunosuppressant agents during breastfeeding is controversial, and there are limited data on safety. We investigated whether biologics are detectable in breast milk from women receiving treatment for inflammatory bowel diseases (IBDs) and whether breastfeeding while receiving treatment is associated with infections or developmental delays. METHODS: We performed a multicenter prospective study of women with IBD and their infants, collecting breast milk samples (n = 72) from patients receiving biologic therapy from October 2013 to November 2015. Drug concentrations were measured in all breast milk samples at several time points within 48 hours of collection and within 168 hours for some samples. Child development was assessed using the Ages and Stages Questionnaire 3, completed by 824 women with IBD (treated or untreated) during pregnancy (620 breastfed, and 204 did not). Data on children's health and development were obtained from mothers and pediatricians, along with information on mothers' medication exposure, IBD history, activity, pregnancy, and postpartum complications. We used chi-squared method or Fisher exact test to determine associations between categorical values and compared differences in continuous outcomes between groups using analysis of variance models. The primary outcome was drug concentration of biologic agents in breast milk (from 72 women) at 1, 12, 24, and 48 hours after dosing and also at 72, 96, 120, and 168 hours for available samples. Secondary outcomes were a range of infant infections and Ages and Stages Questionnaire 3-defined developmental delays among all breastfed infants. RESULTS: We detected infliximab in breast milk samples from 19 of 29 treated women (maximum, 0.74 µg/mL), adalimumab in 2 of 21 treated women (maximum, 0.71 µg/mL), certolizumab in 3 of 13 treated women (maximum, 0.29 µg/mL), natalizumab in 1 of 2 treated women (maximum, 0.46 µg/mL), and ustekinumab in 4 of 6 treated women (maximum, 1.57 µg/mL); we did not detect golimumab in breast milk from the 1 woman receiving this drug. Rates of infection and developmental milestones at 12 months were similar in breastfed vs non-breastfed infants: any infection, 39% vs 39% in control individuals (P > .99) and milestone score, 87 vs 86 in control individuals (P = .9992). Rates of infection and developmental milestones did not differ among infants whose mothers received treatment with biologics, immunomodulators, or combination therapy compared with unexposed infants (whose mothers received treatment with mesalamines or steroids or no medication). CONCLUSIONS: In a study of women receiving treatment for IBD and their infants, we detected low concentrations of infliximab, adalimumab, certolizumab, natalizumab, and ustekinumab in breast milk samples. We found breastfed infants of mothers on biologics, immunomodulators, or combination therapies to have similar risks of infection and rates of milestone achievement compared with non-breastfed infants or infants unexposed to these drugs. Maternal use of biologic therapy appears compatible with breastfeeding. Clinicaltrials.gov no.: NCT00904878.

A Novel Patient-Reported Outcome-Based Evaluation (PROBE) of Quality of Life in Patients With Inflammatory Bowel Disease.

OBJECTIVES: 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. METHODS: Using the Crohn's & Colitis 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. RESULTS: 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, P < 0.001). 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). DISCUSSION: 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.

Impact of Obesity on Disease Activity and Patient-Reported Outcomes Measurement Information System (PROMIS) in Inflammatory Bowel Diseases.

INTRODUCTION: We conducted a cohort study on the impact of obesity on disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) measures in the inflammatory bowel disease (IBD) Partners cohort. METHODS: We performed a cross-sectional and longitudinal study within IBD Partners, an internet-based cohort of >15,000 patients living with Crohn's disease (CD) and ulcerative colitis (UC). We included adult patients with IBD, with recorded body mass index (BMI), with at least 6 months of follow-up, excluding patients with BMI < 18.5 kg/m. We evaluated the independent effect of World Health Organization classes of obesity on risk of clinical relapse or persistent disease activity (using validated disease activity indexes) and PROMIS measures, using multivariate logistic regression and linear regression, respectively. RESULTS: We included 7,296 patients with IBD (4,748 patients with CD, 19.5% obese; 2,548 patients with UC with intact colon, 20.3% obese). Obesity was independently, and in a dose-dependent fashion, associated with an increased risk of persistent disease activity or relapse in both patients with CD (class II or III obesity vs normal BMI: adjusted odds ratio, 1.86; 95% confidence interval, 1.30-2.68) and UC (adjusted odds ratio, 2.97; 95% confidence interval, 1.75-5.17). Obesity was also independently associated with higher anxiety, depression, fatigue, pain, and inferior social function scores in patients with CD and UC at baseline and with worsening depression, fatigue, pain, and social function in patients with CD on longitudinal assessment. DISCUSSION: Obesity at baseline is independently associated with worsening disease activity and PROMIS measures in patients with IBD.

Colonic Diverticula Are Not Associated With Mucosal Inflammation or Chronic Gastrointestinal Symptoms.

BACKGROUND & AIMS: Colonic diverticulosis has been reported to be associated with low-grade mucosal inflammation, possibly leading to chronic gastrointestinal symptoms. However, there is poor evidence for this association. We aimed to determine mucosal inflammation and whether diverticula are associated with chronic gastrointestinal symptoms. We explored whether inflammation was present among symptomatic participants with and without diverticula. METHODS: We analyzed data from a prospective study of 619 patients undergoing a screening colonoscopy from 2013 through 2015 at the University of North Carolina Hospital in Chapel Hill, North Carolina. Among our participants, 255 (41%) had colonic diverticula. Colonic mucosal biopsy specimens were analyzed for levels of interleukin 6 (IL6), IL10, and tumor necrosis factor messenger RNAs by quantitative reverse-transcriptase polymerase chain reaction, and numbers of immune cells (CD4+, CD8+, CD57+, and mast cell tryptase) by immunohistochemistry. Gastrointestinal symptoms were assessed using Rome III criteria. Proportional odds models were used to estimate odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: After adjustment for potential confounders, there was no association between diverticulosis and tumor necrosis factor (OR, 0.85; 95% CI, 0.63-1.16), and no association with CD4+ cells (OR, 1.18; 95% CI, 0.87-1.60), CD8+ cells (OR, 0.97; 95% CI, 0.71-1.32), or CD57+ cells (OR, 0.80; 95% CI, 0.59-1.09). Compared with controls without diverticulosis, biopsy specimens from individuals with diverticulosis were less likely to express the inflammatory cytokine IL6 (OR, 0.59; 95% CI, 0.36-0.96). There was no association between diverticulosis and irritable bowel syndrome (OR, 0.53; 95% CI, 0.26-1.05) or chronic abdominal pain (OR, 0.68; 95% CI, 0.38-1.23). There was no evidence for inflammation in patients with symptoms when patients with vs without diverticulosis were compared. CONCLUSIONS: We found no evidence that colonic diverticulosis is associated with mucosal inflammation or gastrointestinal symptoms. Among patients with symptoms and diverticula, we found no mucosal inflammation.

Evaluation of Gastrointestinal Patient Reported Outcomes Measurement Information System (GI-PROMIS) Symptom Scales in Subjects With Inflammatory Bowel Diseases.

OBJECTIVES: Patient reported outcomes (PROs) are important treatment endpoints in inflammatory bowel diseases (IBD). We evaluated the gastrointestinal (GI) PRO Measurement Information System (PROMIS) in IBD subjects. METHODS: Crohn's and Colitis Foundation of America's Partners is an Internet-based cohort of IBD subjects. Participants complete surveys, including demographics, disease characteristics, PROMIS domains, disease activity (short Crohn's disease activity index or simple clinical colitis activity index) and quality of life (QoL) indices. In a nested cross-sectional study, we used univariate and bivariate analyses to assess associations between 8 GI-PROMIS domains (reflux, swallowing, diarrhea, nausea, belly pain, gas, incontinence, and constipation) and QoL and disease activity indices. RESULTS: The study included 2,378 Crohn's Disease (CD) and 1,455 ulcerative colitis (UC) respondents with a median age of 41 years. Median disease duration was 11 years for CD subjects and 8 years for UC subjects; 57% of CD subjects and 42% of UC subjects were in remission. Among symptomatic CD subjects, those with active CD reported significantly worse symptoms on all 8 domains than those in remission. The same was observed for UC subjects with the exception of disrupted swallowing. IBD subjects with worse QoL reported significantly worse symptoms on all 8 domains compared to those with better QoL. CONCLUSIONS: In IBD subjects experiencing GI symptoms, GI-PROMIS domains were strongly associated with disease activity and QoL indices. GI-PROMIS holds potential as PRO measures in IBD and correlates with other validated indices in this population.

Depression Is Associated With More Aggressive Inflammatory Bowel Disease.

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<0.01). Adjusted for sex, remission, and disease activity, CD patients with baseline depression were at an increased risk for relapse (RR: 2.3; 95% confidence interval (CI): 1.9-2.8), surgery, or hospitalization (RR: 1.3 95% CI: 1.1-1.6) at follow-up. UC patients with baseline depression were also at increased risk for relapse (RR: 1.3; 95% CI: 0.9-1.7), surgery, or hospitalization (RR: 1.3; 95% CI: 1.1-1.5) at follow-up. CONCLUSIONS: Baseline depression is associated with a higher risk for aggressive IBD at follow-up. A single question is not a sensitive method of assessing depression. Providers should consider administering the PHQ-8 to capture those at greater risk for aggressive disease.

Psychometric Evaluation of the IBD-Specific Anxiety Scale: A Novel Measure of Disease-Related Anxiety for Adolescents With IBD.

Anxiety related to pediatric inflammatory bowel disease (IBD) is a common comorbidity; yet, this construct is understudied because of lack of available valid measurement. Objective: The present study will report the preliminary validation of the 20-item IBD-Specific Anxiety Scale (IBD-SAS) in a large, geographically diverse sample of adolescents aged 12-18 years with IBD. Method: A total of 281 adolescents, ages 12-18 (M = 14.8, SD = 1.78; 51% male), completed the IBD-SAS along with measures of IBD-related quality of life, anxiety, depressive symptoms, and disease activity. Factor structure was assessed using exploratory and confirmatory factor analyses (EFA and CFA). Results: EFA (Sample 1; n = 141) yielded one-, two-, three- and four-factor models. The CFA (Sample 2; n = 140) demonstrated that a four-factor model was superior to three- and two-factor model for the amended scale. In total, the IBD-SAS showed excellent internal consistency (Cronbach's α = .95) and was most strongly associated with health-related quality of life. Moderate to strong associations were observed between IBD-SAS and general measures of anxiety and depressive symptoms, and IBD disease activity providing additional support that health-specific anxiety is a valid and distinct construct. Conclusions: Based on the results of this study, the IBD-SAS displayed adequate psychometric properties and can meaningfully contribute to the assessment of IBD-specific anxiety in adolescents diagnosed with IBD, thus filling an empirical and clinical need in this population.

The Burden of Hospital Readmissions among Pediatric Patients with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate the burden and predictors of hospital readmissions among pediatric patients with inflammatory bowel disease using the Nationwide Readmissions Database. STUDY DESIGN: We performed a retrospective cohort study using 2013 Nationwide Readmissions Database. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients <18 years with diagnoses of ulcerative colitis (UC) or Crohn's disease (CD). Demographic factors and details of hospitalizations were evaluated using survey procedures in SAS v 9.4 (SAS Institute, Cary, North Carolina). Multivariable logistic regression was used to estimate ORs and 95% CIs of readmission. RESULTS: Among 2733 hospitalizations (63% CD, 37% UC), 611 (22%) patients were readmitted within 90 days of the index hospitalization. Readmission resulted in weighted estimates of 11 440 excess days of hospitalization and total charges of over $107 million. For CD, male sex (aOR 1.36, 95% CI 1.03-1.81) and co-existing anxiety or depression (aOR 1.89, 95% CI 1.06-3.40) were associated with increased readmissions, while patients who underwent surgery had decreased readmissions (aOR 0.40, 95% CI 0.24-0.65). In patients with UC, an index admission of >7 days was associated with increased readmissions (aOR 1.69, 95% CI 1.09-2.62). CONCLUSIONS: Readmission occurs frequently in children with inflammatory bowel disease and is associated with significant cost and resource burdens. Among patients with CD, psychiatric comorbidities such as anxiety and depression are apparent drivers of readmission.

Inadequate Gestational Weight Gain Predicts Adverse Pregnancy Outcomes in Mothers with Inflammatory Bowel Disease: Results from a Prospective US Pregnancy Cohort.

BACKGROUND: Malnutrition and weight loss are common features of patients with inflammatory bowel disease (IBD). AIM: To explore the impact of inadequate gestational weight gain (GWG) on adverse outcomes among IBD mothers in the prospective US pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) cohort. METHODS: The PIANO cohort comprises 559 and 363 pregnant mothers with Crohn's disease (CD) and ulcerative colitis (UC), respectively, enrolled between 2006 and 2014. The mothers were followed during and after pregnancy to ascertain medication, measurement of disease activity and complications during pregnancy and at delivery. Inadequate GWG was based on US Institute of Medicine recommendations. The associations between inadequate GWG and adverse pregnancy outcomes in maternal IBD were analyzed, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity. RESULTS: Maternal CD and UC with inadequate GWG had a 2.5-fold increased risk of preterm birth (OR 2.5, CI 1.3, 4.9 and OR 2.5, CI 1.2, 5.6). Furthermore, an increased risk of intrauterine growth restriction and a trend for small for gestational age were demonstrated in CD but not in UC (OR 3.3, CI 1.1, 10.0, OR 4.5, CI 0.8, 24.3, p = 0.08). Flares increased risk of inadequate GWG (OR 1.6, CI 1.2, 2.3, p = 0.002) but did not change the associations between inadequate GWG and adverse pregnancy outcomes in our models. CONCLUSION: The US PIANO cohort demonstrated that inadequate GWG was a strong independent predictor of adverse pregnancy outcomes in IBD mothers.

Use of an Abdominal Compression Device in Colonoscopy: A Randomized, Sham-Controlled Trial.

BACKGROUND & AIMS: Looping is a common problem during colonoscopy that prolongs procedure time. We aimed to determine the efficacy and safety of ColoWrap, an external abdominal compression device, with respect to insertion time and other procedural outcomes. METHODS: We performed a prospective study of outpatients undergoing elective colonoscopy (40-80 years old; mean age, 60.5 years) at endoscopy facilities in the University of North Carolina Hospitals from April 2013 through March 2014. Subjects were randomly assigned to groups that received either ColoWrap (n = 175) or a sham device (control, n = 175) during colonoscopy. Colonoscopists and staff were blinded to the application. The primary outcome was cecal intubation time (CIT). Secondary outcomes included use of manual pressure and position change. RESULTS: The mean CIT was similar for the control and ColoWrap groups (6.69 vs 6.67 minutes; P = .98). There were no statistical differences in the frequency of manual pressure (45% for controls vs 37% for ColoWrap group, P = .13) or position changes (4% for controls vs 2% for ColoWrap group, P = .36). Among patients with body mass index between 30 and 40 kg/m(2) (n = 78), CIT was significantly lower for patients in the ColoWrap group (4.69 minutes) than controls (6.10 minutes) (P = .03). Adverse events were similar between groups. CONCLUSIONS: In patients undergoing elective colonoscopy, application of an external abdominal compression device did not improve CIT or affect the frequency of ancillary maneuvers. A possible benefit was observed in patients with body mass index between 30 and 40 kg/m(2), but further studies are needed. ClinicalTrials.gov number: NCT02025504.

Distribution and Characteristics of Colonic Diverticula in a United States Screening Population.

BACKGROUND & AIMS: Colonic diverticula are the most common finding from colonoscopy examinations. Little is known about the distribution of colonic diverticula, which are responsible for symptomatic and costly diverticular disease. We aimed to assess the number, location, and characteristics of colonic diverticula in a large US screening population. METHODS: We analyzed data from a prospective study of 624 patients (mean age, 54 years) undergoing screening colonoscopy at the University of North Carolina Hospital from 2013 through 2015. The examination included a detailed assessment of colonic diverticula. To assess the association between participant characteristics and diverticula, we used logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: Of our population, 260 patients (42%) had 1 or more diverticula (mean number, 14; range, 1-158). Participants with diverticula were more likely to be older, male, and have a higher body mass index than those without diverticula. The distribution of diverticula differed significantly by race. Among white persons, 75% of diverticula were in the sigmoid colon, 11% in the descending splenic flexure, 6% in the transverse colon, and 8% were in the ascending colon or hepatic flexure. In black persons 64% of diverticula were in the sigmoid colon, 8% in the descending colon or splenic flexure, 7% in the transverse colon, and 20% in the ascending colon or hepatic flexure (P = .0008). The proportion of patients with diverticula increased with age: 35% were 50 years or younger, 40% were 51-60 years, and 58% were older than 60 years. The proportion of patients with more than 10 diverticula increased with age: 8% were 50 years or younger, 15% were 51-60 years, and 30% were older than 60 years. CONCLUSIONS: Older individuals not only have a higher prevalence of diverticula than younger individuals, but also a greater density, indicating that this is a progressive disease. Black persons have a greater percentage of their diverticula in the proximal colon and fewer in the distal colon compared with white persons. Understanding the distribution and determinants of diverticula is the first step in preventing diverticulosis and its complications.

Association Between Affective-Cognitive Symptoms of Depression and Exacerbation of Crohn's Disease.

OBJECTIVES: 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. METHODS: We studied 2,144 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD status, and an affective-cognitive index of depression. Linear and logistic regression analyses were used to determine whether CD status at 12 months was associated with the baseline measure of depression. Analyses were adjusted for confounders including age, gender, race, baseline disease activity, disease duration, prior hospitalization and surgery, corticosteroid and anti-TNF use, medication adherence, body mass index, current smoking, education, and sleep quality. RESULTS: Depression was significantly associated with subsequent increases in SCDAI score in both unadjusted (P<0.001) and adjusted (P<0.001) analyses. This association was non-linear, with a shallower slope for lower levels of depression. A 10-point increase in depression t-scores from 55 to 65 was associated with a 18.6-point increase in SCDAI (95% CI 11.5-25.6) and an odds ratio of 1.27 for SCDAI>150 at follow-up (CI: 1.01-1.60). We also found a significant association between depressive symptoms and hospitalization. CONCLUSIONS: Cognitive-affective depressive symptoms were significantly associated with a risk of exacerbation of CD and hospitalization.

Patient-Reported Outcomes Measurement Information System in Children with Crohn's Disease.

OBJECTIVES: To assess the criterion validity and responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) in a web-based cohort of children with Crohn's disease. STUDY DESIGN: We recruited children with Crohn's disease (ages 9-17 years) and their parents from the web-based Crohn's and Colitis Foundation of America Kids and Teens Study cohort. Upon entry into the cohort and 6 months later, children self-reported Crohn's disease activity, health-related quality of life, and PROMIS domains of pain interference, anxiety, depression, fatigue, and peer relationships. RESULTS: Mean PROMIS scores for the 276 participating patients were worse among those with worse self-reported Crohn's disease activity (per Short Crohn's Disease Activity Index, P < .005 for all), Crohn's disease activity in the prior 6 months (per Manitoba Index, P < .01 for all), and health-related quality of life (per IMPACT-35, P < .001 for all). One hundred forty-three patients and their parents completed follow-up questionnaires, 75% of whom reported stable disease activity. Those with improved Crohn's disease activity reported improved PROMIS scores, and those with worsened Crohn's disease activity reported worse PROMIS scores for all domains except anxiety. All participants reported improved anxiety from baseline, but those with stable or worsened Crohn's disease activity reported less improvement (P = .07). CONCLUSIONS: PROMIS scores were significantly associated with Crohn's disease activity in a linear and clinically meaningful manner, and responded to change in Crohn's disease activity over a 6-month period. This supports the criterion validity and responsiveness of pediatric PROMIS.

High-sensitive C-Reactive Protein as a Marker for Inflammation in Irritable Bowel Syndrome.

BACKGROUND: Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses. GOALS: To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities. STUDY: This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities. RESULTS: A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P<0.006). Levels were highest in IBS-D patients with greater disease severity. Hs-CRP levels mildly correlated with symptoms severity (r=0.169, P=0.009); this correlation was stronger for the IBS-D patients (r=0.27, P=0.006). IBS was a significant independent predictor (P=0.025) for higher hs-CRP levels, whereas other pain and psychological comorbidities were not. CONCLUSIONS: Given these observations of cross-sectional differences in hs-CRP between IBS subtypes and severity, independent of pain and comorbidities, more research is needed to explore a possible role of low-grade inflammation in the pathogenesis and/or clinical presentation of IBS.

Role of Nonsteroidal Anti-Inflammatory Drugs in Exacerbations of Inflammatory Bowel Disease.

GOALS: To determine the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in activation of inflammatory bowel disease (IBD). BACKGROUND: NSAIDs may activate inflammatory pathways in IBD. STUDY: Crohn's and Colitis Foundation of American Partners is an ongoing cohort study of patients living with IBD. All data are self-reported using the internet. We identified a subcohort of participants whose disease activity, based on short Crohn's Disease Activity Index and simple clinical colitis activity index, indicated remission. Pattern of use of NSAIDs was measured at baseline, and disease activity assessment was performed 6 months later. We used multivariate binomial regression to determine effects of NSAIDs on disease activity. RESULTS: A total of 791 individuals in remission had baseline and follow-up data available for analysis. Of these, 247 Crohn's disease (CD) patients (43.2%) and 89 ulcerative colitis (UC) patients (40.6%) reported NSAID use. CD patients with NSAID use ≥5 times/month had greater risk of active disease at follow-up (23% vs. 15%, P=0.04); [adjusted risk ratio (RR), 1.65; 95% confidence interval (CI), 1.12-2.44). No effect was observed in patients with UC (22% vs. 21%, P=0.98; adjusted RR, 1.25; 95% CI, 0.81-1.92). Acetaminophen use was associated with active disease at follow-up in CD (adjusted RR, 1.72; 95% CI, 1.11-2.68). CONCLUSIONS: Regular (≥5 times/mo) NSAID and acetaminophen use were associated with active CD, but not UC. Less frequent NSAID use was not associated with active CD or UC. These findings indicate that regular NSAID use may increase CD activity, or that NSAID use may be a marker of a less robust remission; thus reflecting subclinical disease activity.

Prevalence of Eosinophilic Gastritis, Gastroenteritis, and Colitis: Estimates From a National Administrative Database.

OBJECTIVES: Eosinophilic esophagitis (EoE) is becoming increasingly more common, but the prevalence of other eosinophilic gastrointestinal disorders (EGIDs) is unknown. Our objective was to estimate the prevalence of eosinophilic gastritis, gastroenteritis, and colitis in the United States. METHODS: We used the IMS Health LifeLink PharMetrics Plus Claims Database, data representative of a US national commercially insured population containing medical and pharmaceutical claims for > 75 million individuals. We restricted our sample to patients ages 0 to 64 with continuous enrollment between July 1, 2009, and June 30, 2011. We identified patients with eosinophilic gastritis, gastroenteritis, and colitis as defined by ≥ 1 instance of the International Classification of Diseases, Ninth Revision codes 535.70, 558.41, and 558.42, respectively. We calculated the prevalence of the codes in the database and then standardized the estimates to the US population by age and sex. RESULTS: The standardized estimated prevalences of eosinophilic gastritis, gastroenteritis, and colitis were 6.3/100,000, 8.4/100,000, and 3.3/100,000, respectively. The prevalence of eosinophilic gastroenteritis was the highest among children age < 5 years, whereas eosinophilic gastritis was more prevalent among older age groups. We observed no age differences for eosinophilic colitis. Among affected patients, there was a high proportion of coexisting allergic conditions, 38.5% for eosinophilic gastritis, 45.6% for gastroenteritis, and 41.8% for colitis. Concomitant allergic disease was most commonly identified in pediatric patients. CONCLUSIONS: The prevalence of non-EoE EGIDs remains rare in the United States, with < 50,000 total patients affected. There appears to be a female predominance and a high co-occurrence of atopic comorbidities.