The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

Surgery for Crohn's Disease Is Associated with a Dysbiotic Microbiome and Metabolome: Results from Two Prospective Cohorts.

BACKGROUND AND AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, E lenta, A equalofaciens and G pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In two different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria as well as secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.

Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.

Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation. We also uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut. Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health.

Crohn's disease shared decision making intervention leads to more patients choosing combination therapy: a cluster randomised controlled trial.

BACKGROUND: Crohn's disease requires effective patient-clinician communication for successful illness and medication management. Shared decision making (SDM) has been suggested to improve communication around early intensive therapy. However, effective evidence-based SDM interventions for Crohn's disease are lacking, and the impact of SDM on Crohn's disease decision making and choice of therapy is unclear. AIM: To test the impact of SDM on choice of therapy, quality of the decision and provider trust compared to standard Crohn's disease care. METHODS: We conducted a multi-site cluster randomised controlled trial in 14 diverse gastroenterology practices in the US. RESULTS: A total of 158 adult patients with Crohn's disease within 15 years of their diagnosis, with no prior Crohn's disease complications, and who were candidates to receive immunomodulators or biologics, participated in the study. Among these, 99 received the intervention and 59 received standard care. Demographics were similar between groups, although there were more women assigned to standard care, and a slightly shorter disease duration among those in the intervention group. Participants in the intervention group more frequently chose combination therapy (25% versus 5% control, p < 0.001), had a significantly lower decisional conflict (p < 0.05) and had greater trust in their provider (p < 0.05). CONCLUSIONS: With rapidly expanding medication choices for Crohn's disease and slow uptake of early intensive therapy, SDM can personalise treatment strategies and has the potential to move the field of Crohn's disease management forward with an ultimate goal of consistently treating this disease early and intensively in appropriate patients. TRIAL REGISTRATION: Evaluating a Shared Decision Making Program for Crohn's Disease, ClinicalTrials.gov Identifier NCT02084290 https://clinicaltrials.gov/ct2/show/NCT02084290.

An Expert Consensus to Standardize Assessment of Bowel Cleansing for Clinical Trials of Bowel Preparations for Crohn's Disease.

BACKGROUND: Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures. AIMS: To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process. METHODS: Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale. RESULTS: Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed. CONCLUSIONS: We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies.

Efficacy of a Digital Personalized Elimination Diet for the Self-Management of Irritable Bowel Syndrome and Comorbid Irritable Bowel Syndrome and Inflammatory Bowel Disease.

INTRODUCTION: Most patients with irritable bowel syndrome (IBS) and dual-diagnosis IBS and inflammatory bowel disease (IBD) report that symptoms originate from or are exacerbated by trigger foods. Despite patient interest and need, there is no consensus on what diet is optimal. Popular diets have notable limitations including cost, length, implementation complexity, and lack of personalization. METHODS: This pilot study evaluated the feasibility, desirability, and effect on gastrointestinal symptoms of a digitally delivered personalized elimination diet for patients with IBS and comorbid IBS/IBD, powered by machine learning. Participants were recruited online and were provided access to a digital personalized nutrition tool for 9 weeks (N = 37; IBS only = 16, Crohn's disease and IBS = 9, and ulcerative colitis and IBS = 12). RESULTS: Significant symptom improvement was seen for 81% of participants at study midpoint and persisted for 70% at end point, measured by the relevant symptom severity score (IBS symptom severity score, Patient Simple Clinical Colitis Activity Index, or Mobile Health Index for Crohn's disease). Clinically significant symptom improvement was observed in 78% of participants at midpoint and 62% at end point. Twenty-five participants (67.6%) achieved total symptomatic resolution by the end of study. Patient-reported quality of life improved for 89% of participants. Ninety-five percentage daily engagement, 95% retention, 89% adherence and 92% satisfaction with the program were reported. DISCUSSION: Dietary elimination can improve symptoms and quality of life in patients with IBS and comorbid IBS/IBD. Digital technology can personalize dietary interventions and improve adherence. Randomized controlled trials are warranted.

Metabolic analyses reveal dysregulated NAD+ metabolism and altered mitochondrial state in ulcerative colitis.

Ulcerative colitis (UC) is a complex, multifactorial disease driven by a dysregulated immune response against host commensal microbes. Despite rapid advances in our understanding of host genomics and transcriptomics, the metabolic changes in UC remain poorly understood. We thus sought to investigate distinguishing metabolic features of the UC colon (14 controls and 19 patients). Metabolomics analyses revealed inflammation state as the primary driver of metabolic variation rather than diagnosis, with multiple metabolites differentially regulated between inflamed and uninflamed tissues. Specifically, inflamed tissues were characterized by reduced levels of nicotinamide adenine dinucleotide (NAD+) and enhanced levels of nicotinamide (NAM) and adenosine diphosphate ribose (ADPr). The NAD+/NAM ratio, which was reduced in inflamed patients, served as an effective classifier for inflammation in UC. Mitochondria were also structurally altered in UC, with UC patient colonocytes displaying reduced mitochondrial density and number. Together, these findings suggest a link between mitochondrial dysfunction, inflammation, and NAD+ metabolism in UC.

Disease Burden and Patient-Reported Outcomes Among Ulcerative Colitis Patients According to Therapy at Enrollment Into CorEvitas' Inflammatory Bowel Disease Registry.

Background: To evaluate disease burden and patient-reported outcomes (PROs) of ulcerative colitis (UC) patients at enrollment into CorEvitas' Inflammatory Bowel Disease Registry by therapy class. Methods: Between May 3, 2017 and September 3, 2019, 773 UC registry patients were categorized by therapy class at enrollment: patients on 5-aminosalicylic acids (5-ASAs) only (n = 290), and patients on biologics/Janus kinase inhibitors (JAKi) alone or in combination with 5-ASAs or immunosuppressant therapies (BIO/JAKi) (n = 315). To quantify between group differences, the mean/proportional differences and corresponding 95% CIs were calculated. Results: Among 605 UC patients at enrollment, BIO/JAKi patients were younger (44.1 vs. 50.9 years) more were female (58.0% vs. 49.7%), had lower remission (45.4% vs. 60.0%), had more moderate/severe disease (16.5% vs. 7.1%), experienced less proctitis (10.5% vs. 22.1%), but more pancolitis (54.6% vs. 34.1%), more corticosteroid experience (70.8% vs. 44.5%), previous biologic experience (1 prior: 21.6% vs. 2.4%; 2+ prior: 12.1% vs. 0.3%), and shorter duration of current UC therapy (1.6 vs. 3.5 years) than 5-ASAs patients. BIO/JAKi patients had higher current employment than 5-ASAs patients (70.7% vs. 62.4%) and higher mean Work Productivity and Activity Impairment (WPAI) domains for absenteeism (7.3 vs. 2.8) and activity impairment (22.0 vs. 17.5). Conclusions: Among UC patients in a real-world setting, BIO/JAKi patients had less remission, more moderate-to-severe disease, and worse PROs than 5-ASAs patients. These results suggest that despite increased therapeutic options, patients with UC currently being treated with biologics or JAKi may still experience disease burden and continued unmet needs.

Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data.

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.

Heparin-Coated Albumin Nanoparticles for Drug Combination in Targeting Inflamed Intestine.

Targeting areas of inflammation offers potential therapeutic and diagnostic benefits by maximizing drug and imaging marker on-target effects while minimizing systemic exposure that can be associated with adverse side effects. This strategy is particularly beneficial in the management of inflammatory bowel disease (IBD). Here an inflammation-targeting (IT) approach based on heparin-coated human serum albumin nanoparticles (HEP-HSA NPs) that utilize the increased intestinal permeability and changes in electrostatic interaction at the site of intestinal inflammation is described. Using small-molecule and biologic drugs as a model for drug combination, the HEP-HSA NPs demonstrate the capacity to load both drugs simultaneously; the dual-drug loaded HEP-HSA NPs exhibit a higher anti-inflammatory effect than both of the single-drug loaded NPs in vitro and selectively bind to inflamed intestine after enema administration in vivo in a murine model of colitis. Importantly, analyses of the physicochemical characteristics and targeting capacities of these NPs indicate that HEP coating modulates NP binding to the inflamed intestine, providing a foundation for future IT-NP formulation development.

Immunologic Alterations Associated With Oral Delivery of Anti-CD3 (OKT3) Monoclonal Antibodies in Patients With Moderate-to-Severe Ulcerative Colitis.

AIM: The aim of this study was to determine the immunologic effects and safety of oral anti-CD3 in patients with ulcerative colitis (UC). METHODS: An open-label pilot study of orally delivered anti-CD3 was performed in patients with moderate-to-severe UC. The primary end points were changes in immunologic parameters and evaluation for safety. RESULTS: Six subjects received oral OKT3. Biologic effects of oral anti-CD3 included significantly increased proliferation in response to anti-CD3 and anti-inflammatory gene expression profile in peripheral blood mononuclear cells. No serious treatment-related adverse events occurred. CONCLUSION: Orally delivered anti-CD3 resulted in immunologic changes in patients with UC.

Challenges in IBD Research: Environmental Triggers.

Environmental triggers is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the environmental triggers section is focused on the main research gaps in elucidating causality of environmental factors in IBD. Research gaps were identified in: 1) epidemiology of exposures; 2) identification of signatures of biological response to exposures; and 3) mechanisms of how environmental exposures drive IBD. To address these gaps, the implementation of longitudinal prospective studies to determine disease evolution and identify sub-clinical changes in response to exposures is proposed. This can help define critical windows of vulnerability and risk prediction. In addition, systems biology analysis and in silico modeling were proposed as approaches to integrate the IBD exposome for the identification of biological signatures of response to exposures, and to develop prediction models of the effects of environmental factors in driving disease activity and response to therapy. This research could lead to identification of biomarkers of exposures and new modalities for therapeutic intervention. Finally, hypothesis-driven mechanistic studies to understand gene-environment interactions and to validate causality of priority factors should be performed to determine how environment influences clinical outcomes.

Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT. METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed. RESULTS: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02). DISCUSSION: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.

Dibutyl-phthalate exposure from mesalamine medications and serum thyroid hormones in men.

BACKGROUND: Dibutyl phthalate (DBP) is an endocrine disruptor and used in some medication coatings, such as mesalamine for treatment inflammatory bowel disease (IBD). OBJECTIVES: To determine whether high-DBP from some mesalamine medications alters thyroid function. METHODS: Seventy men with IBD, without thyroid disease or any radiation history participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background exposure) at baseline crossed-over to DBP-mesalamine (high exposure) then crossed-back to non-DBP mesalamine (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). Serum concentrations of total triiodothyronine (T3), total thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). RESULTS: After crossover in B1HB2-arm (26 men, 134 samples), T3 decreased 10% (95% confidence interval (CI): 14%,-5%), T3/T4 ratio decreased 8% (CI: 12%,-3%), TPOAb, and TgAb concentrations decreased, 11% (-20%, -2%) and 15% (-23%, -5%), respectively; after crossback, they increased. When men in the H1BH2-arm (44 men, 193 samples) crossed-over, T3 decreased 7% (CI: -11%, -2%) and T3/T4 ratio decreased 6% (CI: -9%, -2%). After crossback, only TgAb increased and FT4 decreased. CONCLUSIONS: High-DBP novel exposure or removal from chronic high-DBP exposure could alter elements of the thyroid system, and most probably alters the peripheral T4 conversion to T3 and thyroid autoimmunity, consistent with thyroid disruption. After exposure removal, these trends were mostly reversed.

Mucosal Gene Expression in Pediatric and Adult Patients With Ulcerative Colitis Permits Modeling of Ideal Biopsy Collection Strategy for Transcriptomic Analysis.

Background: Transcriptional profiling has been performed on biopsies from ulcerative colitis patients. Limitations in prior studies include the variability introduced by inflammation, anatomic site of biopsy, extent of disease, and medications. We sought to more globally understand the variability of gene expression from patients with ulcerative colitis to advance our understanding of its pathogenesis and to guide clinical study design. Methods: We performed transcriptional profiling on 13 subjects, including pediatric and adult patients from 2 hospital sites. For each patient, we collected 6 biopsies from macroscopically inflamed tissue and 4 biopsies from macroscopically healthy-appearing tissue. Isolated RNA was used for microarray gene expression analysis utilizing Affymetrix Human Primeview microarrays. Ingenuity pathway analysis was used to assess over-representation of gene ontology and biological pathways. RNAseq was also performed, and differential analysis was assessed to compare affected vs unaffected samples. Finally, we modeled the minimum number of biopsies required to reliably detect gene expression across different subject numbers. Results: Transcriptional profiles co-clustered independently of the hospital collection site, patient age, sex, and colonic location, which parallels prior gene expression findings. A small set of genes not previously described was identified. Our modeling analysis reveals the number of biopsies and patients per cohort to yield reliable results in clinical studies. Conclusions: Key findings include concordance, including some expansion, of previously published gene expression studies and similarity among different age groups. We also established a reliable statistical model for biopsy collection for future clinical studies.

A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men.

BACKGROUND: Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD). OBJECTIVES: Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (>1000x background) altered serum hormones. METHODS: Men (N=73) with IBD participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background) at baseline crossed-over for 4 months to DBP-mesalamine (high) and then crossed-back for 4 months to non-DBP mesalamine (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). We divided H1BH2-arm at the median (H1<3yrs or H1≥3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models. RESULTS: When B1HB2-arm (26 men,134 samples) crossed-over, luteinizing hormone decreased 13.9% (95% confidence interval(CI): -23.6,-3.0) and testosterone, inhibin-B, and follicle-stimulating hormone (FSH) marginally decreased; after crossback all increased 8-14%. H1BH2-arm, H1≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H1BH2-arm,H1<3yrs (22 men,100 samples) after crossover, inhibin-B increased 13.2% (CI: 4.2,22.9), FSH decreased 9.9% (CI: -17.9,-1.1) and after crossback, inhibin-B further increased 11.3%, and FSH marginally increased. CONCLUSIONS: High-DBP exposure may disrupt pituitary-gonadal hormones that largely reversed after exposure removal, but only in men with no or short previous high-exposure history. Paradoxically, men with longer duration of high-DBP exposure, exposure removal did not change hormone levels, suggesting that long-term high-DBP exposure may alter the pituitary-gonadal axis and make it insensitive to exposure changes.

A probabilistic pathway score (PROPS) for classification with applications to inflammatory bowel disease.

Summary: Gene-based supervised machine learning classification models have been widely used to differentiate disease states, predict disease progression and determine effective treatment options. However, many of these classifiers are sensitive to noise and frequently do not replicate in external validation sets. For complex, heterogeneous diseases, these classifiers are further limited by being unable to capture varying combinations of genes that lead to the same phenotype. Pathway-based classification can overcome these challenges by using robust, aggregate features to represent biological mechanisms. In this work, we developed a novel pathway-based approach, PRObabilistic Pathway Score, which uses genes to calculate individualized pathway scores for classification. Unlike previous individualized pathway-based classification methods that use gene sets, we incorporate gene interactions using probabilistic graphical models to more accurately represent the underlying biology and achieve better performance. We apply our method to differentiate two similar complex diseases, ulcerative colitis (UC) and Crohn's disease (CD), which are the two main types of inflammatory bowel disease (IBD). Using five IBD datasets, we compare our method against four gene-based and four alternative pathway-based classifiers in distinguishing CD from UC. We demonstrate superior classification performance and provide biological insight into the top pathways separating CD from UC. Availability and Implementation: PROPS is available as a R package, which can be downloaded at http://simtk.org/home/props or on Bioconductor. Contact: rbaltman@stanford.edu. Supplementary information: Supplementary data are available at Bioinformatics online.

Suicidal Behavior Among Hospitalized Adults With Inflammatory Bowel Disease: A United States Nationwide Analysis.

Background: Suicidal behavior in inflammatory bowel disease (IBD) has been minimally explored. We aimed to determine United States (US) nationally representative prevalence estimates of suicidal ideation (SI) and suicide/self-inflicted injury (S/SII) among hospitalized adults with IBD and to examine trends in suicidal behavior over time. Methods: A retrospective cross-sectional study using National (Nationwide) Inpatient Sample data (2006-2011) identified adults with Crohn's disease (CD) or ulcerative colitis (UC), SI or S/SII, and multiple comorbid risk factors for suicidal behavior. Results: We identified 331,777 (estimated 1.64 million) IBD-related hospitalizations (64% CD, 36% UC) and 39,787,239 (estimated 196.08 million) hospitalizations among the general US population. Among IBD-related hospitalizations, 2502 discharges were associated with SI (prevalence 0.76%) and 1104 with S/SII (prevalence 0.33%). Both were significantly greater in CD versus UC (P < 0.001). Relative to the general US population, IBD patients were significantly less likely to demonstrate suicidal behavior: (SI:0.33% versus 0.59%, P < 0.001) (S/SII:0.75% versus 1.04%, P < 0.001). Multivariable logistic regression revealed that IBD was associated with decreased odds of SI (adjusted odds ratio [aOR] 0.62, 95%CI 0.60-0.65) and S/SII (aOR 0.43, 95%CI 0.40-0.45) relative to the general population, and suicidal behavior was lower in IBD compared to disease-related controls with rheumatoid arthritis and systemic lupus erythematosus. Similar increasing trends in suicidal behavior were observed in IBD and non-IBD populations (2006-2011). Conclusion: In this large US database, SI or S/SII occurred in over 1% of the IBD population and was increased in CD versus UC.

The Practical Pros and Cons of Complementary and Alternative Medicine in Practice: Integrating Complementary and Alternative Medicine into Clinical Care.

Complementary and alternative medicine (CAM) is changing health care for individuals with inflammatory bowel disease. The move toward increasing patient autonomy and addressing lifestyle and psychosocial factors contributes to this shift. Numerous clinics and centers are offering new models to incorporate these elements. There is need for better and more robust data regarding CAM efficacy and safety. CAM offers a test kitchen for new approaches to care and care delivery, which are now being developed and studied, and has the possibility to affect patient quality of life, disease morbidity, cost, and use of health care.