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Summary: Background: While opioid prescriptions have increased alarmingly in the United States (US), their use for unexplained chronic gastrointestinal (GI) pain (eg, irritable bowel syndrome) carries an especially high risk for adverse effects and questionable benefit. Aim: To compare opioid use among US veterans with structural GI diagnoses (SGID) and those with unexplained GI symptoms or functional GI diagnoses (FGID), a group for whom opioids have no accepted role. Methods: Veterans Health Administration (VHA) administrative data from fiscal year 2012 were used to identify veterans with diagnostic codes recorded for SGID and FGID. This cohort study examined VHA pharmacy data to compare groups receiving ≥ 1 opioid prescription during the year and number of prescriptions filled. Bivariate and multiple logistic regression analyses adjusted for potential confounding factors (demographics, medical diagnoses, social factors) and identified potential mediators (service use, psychiatric comorbidity) of opioid use in these groups. Results: A greater proportion of veterans with FGID received an opioid prescription during fiscal year 2012 (36.0% of 272 431) compared to only 28.9% of 1 223 744 in the SGID group (Relative Risk [RR] = 1.25). In multivariate logistic regression, personality disorders and drug abuse (OR 1.23 for each group), recent homelessness (OR 1.22), psychotropic medication fills (OR 1.55) and emergency department encounters (OR 1.21) were independently associated with opioid prescription use. Conclusions: Despite the potential for adverse consequences, opioids more often are prescribed for veterans with chronic, unexplained GI symptoms compared to those with structural diagnoses. Psychiatric comorbidities and frequent healthcare encounters mediate some of the opioid use risk. [ABSTRACT FROM AUTHOR]

Presents a study which focused on controllability, observability and realizability for first-order time scale dynamical systems of the form xΔ(t) = A(t)x(t) + B(t)U(t), x(t0) = x0, with output signal y(t) = C(t)x(t) and control U(t). Definition of observability; Presentation of some of the basic notions concerning time scales; Formula for (p x n) matrix functions.

Presents a study that introduced a set of ideas in mathematical control theory involving Kronecker products of matrices. Equivalence relation between general Kronecker product first-order systems and its companion vector equation; Formulation of the Kronecker product vector companion system; Discussion on the controllability of the Kronecker product first-order system.

Introduction: Segmentation of dental radiographs is a comprehensive subject in oral care and diagnosis. It is the process of delineating anatomical structures to simplify the diagnostic process for oral and maxillofacial radiologists., Purpose: This paper will provide an in-depth analysis of the latest benchmarks in oral imaging by studying the segmentation of panoramic radiographs using Trainable WEKA (Waikato Environment for Knowledge Analysis) Segmentation (TWS). The aim of this research is to accurately automate segmentation where it can be implemented on a large scale of clients in order to simplify radiological diagnosis., Methods and Materials: The experimentation was conducted by modifying open-source radiographs from UFBA UESC DENTAL IMAGES dataset. In order to simulate realistic conditions such as noise affecting regions of interest, panoramic radiographs were degraded and blurred with Gaussian noise. Accuracy was quantified by measuring the difference between the automated image and the dentist-annotated image using MorphoLibJ. To ensure the precision in results, automated predicted segmentations were observed by an oral maxillofacial radiologist and compared with the dentist-renditioning annotations of the panoramic radiographs (orthopantomograms)., Results: The TWS classifier on radiographs with an average of 32 teeth and greater (Dice value of 0.66) and an average of less than 32 teeth (F1 score of 0.59) was significant. The calculated t-value for the Jaccard index is 2.78 and the t-value for the Dice score is 2.81. The results, considering the statistical scores, were due to the independent variable. The radiographs with 32 teeth and greater had higher Intersection over Union scores and F1 scores because of less discrepancy in tooth alignment., Conclusions: Segmentation of dental radiographs can be conducted by machine learning instead of manual segmentation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kanuri et al.)

Online guided self-help may be an effective and scalable intervention for symptoms of generalized anxiety disorder (GAD) among university students in India. Based on an online screen for GAD administered at 4 Indian universities, 222 students classified as having clinical (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria) or subthreshold (Generalized Anxiety Disorder Questionnaire, Fourth Edition, score ≥ 5.7) GAD were randomly assigned to receive either 3 months of guided self-help cognitive-behavioral therapy (n = 117) or a waitlist control condition (n = 105). Guided self-help participants recorded high program usage on average across all participants enrolled (M = 9.99 hr on the platform; SD = 20.87). Intent-to-treat analyses indicated that participants in the guided self-help condition experienced significantly greater reductions than participants in the waitlist condition on GAD symptom severity (d = -.40), worry (d = -.43), and depressive symptoms (d = -.53). No usage variables predicted symptom change in the guided self-help condition. Participants on average reported that the program was moderately helpful, and a majority (82.1%) said they would recommend the program to a friend. Guided self-help appears to be a feasible and efficacious intervention for university students in India who meet clinical or subthreshold GAD criteria. The trial is registered with ClinicalTrials.gov (NCT02410265). (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Generalised anxiety disorder (GAD) is prevalent among college students in India; however, barriers like stigma, treatment accessibility and cost prevent engagement in treatment. Web- and mobile-based, or digital, mental health interventions have been proposed as a potential solution to increasing treatment access. With the ultimate goal of developing an engaging digital mental health intervention for university students in India, the current study sought to understand students' reactions to a culturally and digitally adapted evidence-based cognitive behavioural therapy (CBT) for GAD intervention. Specifically, through theatre testing and focus groups with a non-clinical sample of 15 college students in India, the present study examined initial usability, acceptability and feasibility of the "Mana Maali Digital Anxiety Program." Secondary objectives comprised identifying students' perceived barriers to using the program and eliciting recommendations. Results indicated high usability, with the average usability rating ranking in the top 10% of general usability scores. Participants offered actionable changes to improve usability and perceived acceptability among peers struggling with mental health issues. Findings highlight the benefits of offering digital resources that circumvent barriers associated with accessing traditional services. Results build on existing evidence that digital interventions can be a viable means of delivering mental healthcare to large, defined populations., (© 2019 International Union of Psychological Science.)

Background: Disclosure is a difficult but important process for victims of child maltreatment. There is limited research on child maltreatment disclosure. Young people have been reluctant to disclose victimization to adults, but short message service (SMS) crisis services may represent one novel method of engaging young people around sensitive topics., Objective: The purpose of this study was to determine characteristics of child maltreatment disclosure to an SMS-based crisis service., Methods: We conducted a content analysis of all conversations (N=244) that resulted in a mandatory report by an SMS-based crisis service between October 2015 and July 2017. We coded characteristics of the disclosure process, including the reason for initial contact, phrase used to disclose abuse, perpetrator, type of abuse, and length of victimization. After identifying terms used by young people to disclose child abuse, we randomly selected and analyzed 50 conversations using those terms to determine if use of the terms differed between conversations that did and did not result in mandatory report., Results: Parents were the most common perpetrator. Physical abuse was the most common form of abuse discussed in the initial abuse disclosure (106/244, 43.4%), followed by psychological abuse (83/244, 34.0%), sexual abuse (38/244, 15.6%), and neglect (15/244, 6.1%). More than half of the texters discussed abuse or other significant family issues in the first message. An explicit description of the experience or definite language, such as abuse, rape, and molested, was common in disclosures., Conclusions: Early disclosure, combined with explicit language, may suggest at least a portion of young victims are actively seeking safe ways to talk about their experiences with abuse, rather than incidentally sharing experiences while seeking support for other issues. SMS text messaging may be a valuable way to engage with young people around sensitive topics, but these approaches will require careful consideration in their development, implementation, and evaluation to ensure a positive experience for young people., (©Laura Schwab-Reese, Nitya Kanuri, Scottye Cash. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 25.03.2019.)

Data sharing between technology companies and academic health researchers has multiple health care, scientific, social, and business benefits. Many companies remain wary about such sharing because of unaddressed concerns about ethics, data security, logistics, and public relations. Without guidance on these issues, few companies are willing to take on the potential work and risks involved in noncommercial data sharing, and the scientific and societal potential of their data goes unrealized. In this paper, we describe the 18-month long pilot of a data-sharing program led by Crisis Text Line (CTL), a not-for-profit technology company that provides a free 24/7 text line for people in crisis. The primary goal of the data-sharing pilot was to design, develop, and implement a rigorous framework of principles and protocols for the safe and ethical sharing of user data. CTL used a stakeholder-based policy process to develop a feasible and ethical data-sharing program. The process comprised forming a data ethics committee; identifying policy challenges and solutions; announcing the program and generating interest; and revising the policy and launching the program. Once the pilot was complete, CTL examined how well the program ran and compared it with other potential program models before putting in place the program that was most suitable for its organizational needs. By drawing on CTL's experiences, we have created a 3-step set of guidelines for other organizations that wish to develop their own data-sharing program with academic researchers. The guidelines explain how to (1) determine the value and suitability of the data and organization for creating a data-sharing program; (2) decide on an appropriate data sharing and collaboration model; and (3) develop protocols and technical solutions for safe and ethical data sharing and the best organizational structure for implementing the program. An internal evaluation determined that the pilot satisfied CTL's goals of sharing scientific data and protecting client confidentiality. The policy development process also yielded key principles and protocols regarding the ethical challenges involved in data sharing that can be applied by other organizations. Finally, CTL's internal review of the pilot program developed a number of alternative models for sharing data that will suit a range of organizations with different priorities and capabilities. In implementing and studying this pilot program, CTL aimed both to optimize its own future data-sharing programs and to inform similar decisions made by others. Open data programs are both important and feasible to establish. With careful planning and appropriate resources, data sharing between big data companies and academic researchers can advance their shared mission to benefit society and improve lives., (©Anthony R Pisani, Nitya Kanuri, Bob Filbin, Carlos Gallo, Madelyn Gould, Lisa Soleymani Lehmann, Robert Levine, John E Marcotte, Brian Pascal, David Rousseau, Shairi Turner, Shirley Yen, Megan L Ranney. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 17.01.2019.)

Background and Aims: Coeliac disease (CD) is widely prevalent in North America, but case-finding techniques currently used may not be adequate for patient identification. We aimed to determine the adequacy of CD screening in an academic gastroenterology (GI) practice., Methods: Consecutive initial visits to a tertiary academic GI practice were surveyed over a 3-month period as a fellow-initiated quality improvement project. All electronic records were reviewed to look for indications for CD screening according to published guidelines. The timing of screening was noted (before or after referral), as well as the screening method (serology or biopsy). Data were analysed to compare CD screening practices across subspecialty clinics., Results: 616 consecutive patients (49±0.6 years, range 16-87 years, 58.5% females, 94% Caucasian) fulfilled inclusion criteria. CD testing was indicated in 336 (54.5%), but performed in only 145 (43.2%). The need for CD screening was highest in luminal GI and inflammatory bowel disease clinics, followed by biliary and hepatology clinics (p<0.0001); CD screening rate was highest in the luminal GI clinic (p=0.002). Of 145 patients screened, 4 patients (2.4%) had serology consistent with CD, of which 2 were proven by duodenal biopsy. Using this proportion, an additional 5 patients might have been diagnosed in 191 untested patients with indications for CD screening., Conclusions: More than 50% of patients in a tertiary GI clinic have indications for CD screening, but <50% of indicated cases are screened. Case-finding techniques therefore are suboptimal, constituting a gap in patient care and an important target for future quality improvement initiatives., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: We conducted a meta-review to determine the reporting quality of user-centered digital interventions for the prevention and management of cardiometabolic conditions., Materials and Methods: Using predetermined inclusion criteria, systematic reviews published between 2010 and 2015 were identified from 3 databases. To assess whether current evidence is sufficient to inform wider uptake and implementation of digital health programs, we assessed the quality of reporting of research findings using (1) endorsement of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, (2) a quality assessment framework (eg, Cochrane risk of bias assessment tool), and (3) 8 parameters of the Consolidated Standards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth (CONSORT-eHEALTH) guidelines (developed in 2010)., Results: Of the 33 systematic reviews covering social media, Web-based programs, mobile health programs, and composite modalities, 6 reported using the recommended PRISMA guidelines. Seven did not report using a quality assessment framework. Applying the CONSORT-EHEALTH guidelines, reporting was of mild to moderate strength., Discussion: To our knowledge, this is the first meta-review to provide a comprehensive analysis of the quality of reporting of research findings for a range of digital health interventions. Our findings suggest that the evidence base and quality of reporting in this rapidly developing field needs significant improvement in order to inform wider implementation and uptake., Conclusion: The inconsistent quality of reporting of digital health interventions for cardiometabolic outcomes may be a critical impediment to real-world implementation., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Posttraumatic stress disorder (PTSD) is highly prevalent in the population, but relatively few affected individuals receive treatment for it. Smartphone applications (apps) could help address this unmet need by offering sound psychoeducational information and evidence-based cognitive behavioral coping tools. We conducted a randomized controlled trial to assess the efficacy of a free, publicly available smartphone app (PTSD Coach) for self-management of PTSD symptoms., Method: One hundred 20 participants who were an average of 39 years old, mostly women (69.2%) and White (66.7%), recruited primarily through online advertisements, were randomized to either a PTSD Coach (n = 62) or a waitlist condition (n = 58) for 3 months. Web-administered self-report measures of PTSD, PTSD symptom coping self-efficacy, depression, and psychosocial functioning were conducted at baseline, posttreatment, and 3 months following treatment., Results: Following the intent-to-treat principle, repeated-measures analyses of variance (ANOVAs) revealed that at posttreatment, PTSD Coach participants had significantly greater improvements in PTSD symptoms (p = .035), depression symptoms (p = .005), and psychosocial functioning (p = .007) than did waitlist participants; however, at posttreatment, there were no significant mean differences in outcomes between conditions. A greater proportion of PTSD Coach participants achieved clinically significant PTSD symptom improvement (p = .018) than waitlist participants., Conclusion: PTSD Coach use resulted in significantly greater improvements in PTSD symptoms and other outcomes relative to a waitlist condition. Given the ubiquity of smartphones, PTSD Coach may provide a wide-reaching, convenient public health intervention for individuals with PTSD symptoms who are not receiving care. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background and Aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice., Methods: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study., Results: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated., Conclusions: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aims to evaluate the feasibility and potential effectiveness of two approaches to using the PTSD Coach mobile application in primary care: Self-Managed PTSD Coach and Clinician-Supported PTSD Coach. This study also aims to gather preliminary data to investigate if clinician support improves the benefits of using PTSD Coach on posttraumatic stress disorder (PTSD) severity and specialty mental healthcare utilization., Method: Twenty primary care veterans with PTSD symptoms were randomized to either Self-Managed PTSD Coach consisting of one 10-min session providing instructions for application use or Clinician-Supported PTSD Coach consisting of four 20-min sessions focused on setting symptom reduction goals and helping veterans fully engage with application content., Results: Research procedures and intervention conditions appear feasible as indicated by high rates of assessment and intervention retention and high clinician fidelity and satisfaction. Both treatments resulted in reductions in PTSD symptoms, with 7 Clinician-Supported PTSD Coach and 3 Self-Managed PTSD Coach participants reporting clinically significant improvements. Clinician-Supported PTSD Coach resulted in more specialty PTSD care use postintervention and possibly greater reductions in PTSD symptoms., Conclusions: Both PTSD Coach interventions are feasible and potentially helpful. The addition of clinician support appears to increase the effectiveness of self-management alone. A larger-scale randomized controlled trial is warranted to confirm these encouraging preliminary findings., (Published by Elsevier Inc.)

Background: Generalized anxiety disorder (GAD) is one of the most common mental disorders among university students; however, many students go untreated due to treatment costs, stigma concerns, and limited access to trained mental health professionals. These barriers are heightened in universities in India, where there are scant mental health care services and severe stigma surrounding help seeking., Objective: To evaluate the feasibility, acceptability, and efficacy of Internet-based, or "online," cognitive behavioral therapy (CBT)-based unguided and guided self-help interventions (using the programs GAD Online and Lantern, respectively) to reduce GAD symptoms in students with clinical and subthreshold GAD and, ultimately, reduce the prevalence and incidence of GAD among the student population., Methods: Students will be recruited via 3 colleges in Hyderabad, India, and referred for a campus-wide online screening. Self-report data will be collected entirely online. A total of 300 qualifying students will be randomized in a 1:1:1 ratio to receive GAD Online, Lantern, or to be in a wait-list control condition, stratified by clinical and subthreshold GAD symptomatology. Students will complete a postintervention assessment after 3 months and a follow-up assessment 6 months later, at which point students in the wait-list control condition will receive one of the programs. The primary outcome is GAD symptom severity at 3 months postintervention. Secondary outcomes include GAD caseness at 9 months, other anxiety and depression symptoms, self-efficacy, and functional measures (eg, sleep, social functioning) at 3 and 9 months, respectively. Primary analyses will be differences between each of the intervention groups and the wait-list control group, analyzed on an intention-to-treat (ITT) basis using mixed-design ANOVA., Results: The study commenced in February 2015. The sample was recruited over a 3-week period at each college. The trial is expected to end in December 2015., Conclusions: This trial will be the first to evaluate the use of Internet-based CBT programs compared with a wait-list control group for the treatment of GAD among students in Indian universities. If effective, these programs have the potential to reduce the mental health care treatment gap by providing readily accessible, private, and cost-effective evidence-based care to students with GAD who do not currently receive the treatment they need., Trial Registration: ClinicalTrials.gov NCT02410265 http://clinicaltrials.gov/ct2/show/NCT02410265 (Archived by WebCite at http://www.webcitation.org/6ddqH6Rbt).

Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders on college campuses and often goes unidentified and untreated. We propose a combined prevention and treatment model composed of evidence-based self-help (SH) and guided self-help (GSH) interventions to address this issue. To inform the development of this stepped-care model of intervention delivery, we evaluated results from a population-based anxiety screening of college students. A primary model was developed to illustrate how increasing levels of symptomatology could be linked to prevention/treatment interventions. We used screening data to propose four models of classification for populations at risk for GAD. We then explored the cost considerations of implementing this prevention/treatment stepped-care model. Among 2489 college students (mean age 19.1 years; 67% female), 8.0% (198/2489) met DSM-5 clinical criteria for GAD, in line with expected clinical rates for this population. At-risk Model 1 (subthreshold, but considerable symptoms of anxiety) identified 13.7% of students as potentially at risk for developing GAD. Model 2 (subthreshold, but high GAD symptom severity) identified 13.7%. Model 3 (subthreshold, but symptoms were distressing) identified 12.3%. Model 4 (subthreshold, but considerable worry) identified 17.4%. There was little overlap among these models, with a combined at-risk population of 39.4%. The efficiency of these models in identifying those truly at risk and the cost and efficacy of preventive interventions will determine if prevention is viable. Using Model 1 data and conservative cost estimates, we found that a preventive intervention effect size of even 0.2 could make a prevention/treatment model more cost-effective than existing models of "wait-and-treat.", (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT., Methods: Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder., Results: The total group agreement was moderate (κ=0.57; 95% CI: 0.56-0.59) for EPT and fair (κ=0.32; 0.30-0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65-0.71) for EPT and moderate (κ=0.46; 0.43-0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45-0.50) for EPT and poor to fair (κ=0.20; 0.17-0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4-4.5; P<0.0001), and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT (OR: 3.4; 2.4-5.0; P<0.0001)., Conclusions: Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses were demonstrated with analysis using EPT over CLT among our selected raters. On the basis of these findings, EPT may be the preferred assessment modality of esophageal motility.

Background: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Genetic polymorphisms can confer CD risk and influence disease phenotype. Indoleamine 2,3 dioxygenase-1 (IDO1) is one of the most over-expressed genes in CD and mediates potent anti-inflammatory effects via tryptophan metabolism along the kynurenine pathway. We aimed to determine whether non-synonymous polymorphisms in IDO1 or IDO2 (a gene paralog) are important either as CD risk alleles or as modifiers of CD phenotype., Methods: Utilizing a prospectively collected database, clinically phenotyped CD patients (n = 734) and non-IBD controls (n = 354) were genotyped for established IDO1 and IDO2 non-synonymous single nucleotide polymorphisms (SNPs) and novel genetic variants elucidated in the literature. Allelic frequencies between CD and non-IBD controls were compared. Genotype-phenotype analysis was conducted. IDO1 enzyme activity was assessed by calculating the serum kynurenine to tryptophan ratio (K/T)., Results: IDO1 SNPs were rare (1.7% non-IBD vs 1.1% CD; p = NS) and not linked to Crohn's disease diagnosis in this population. IDO1 SNPs did however associate with a severe clinical course, presence of perianal disease, extraintestinal manifestations and a reduced serum K/T ratio during active disease suggesting lower IDO1 function. IDO2 minor allele variants were common and one of them, rs45003083, associated with reduced risk of Crohn's disease (p = 0.025). No IDO2 SNPs associated with a particular Crohn's disease clinical phenotype., Conclusions: This work highlights the functional importance of IDO enzymes in human Crohn's disease and establishes relative rates of IDO genetic variants in a US population.

Background: Tricyclic antidepressants (TCAs) have efficacy in treating irritable bowel syndrome (IBS). Some clinicians use TCAs to treat residual symptoms in inflammatory bowel disease (IBD) patients already on decisive IBD therapy or with quiescent inflammation, although this strategy has not been formally studied., Goals: The aim of this study was to examine the efficacy of TCA therapy in IBD patients with residual symptoms, despite controlled inflammation, in a retrospective cohort study., Study: Inclusion required initiation of TCA for persistent gastrointestinal symptoms. IBD patients had inactive or mildly active disease with persistent symptoms despite adequate IBD therapy as determined by their physician. Symptom response was compared with IBS patients. Established Likert scales were used to score baseline symptom severity (0=no symptoms, 3=severe symptoms) and TCA response (0=no improvement; 3=complete satisfaction)., Results: Eighty-one IBD [41.3±1.7 y, 56F; 58 Crohn's disease/23 ulcerative colitis (UC)] and 77 IBS (46.2±1.7 y, 60F) patients were initiated on a TCA therapy. Baseline symptom scores (IBD, 2.06±0.03; IBS, 2.12±0.04; P=0.15) and symptom response to TCA therapy (IBD, 1.46±0.09; IBS, 1.30±0.09; P=0.2) were similar in both the groups. At least moderate improvement (Likert score ≥2) on TCA was achieved by comparable proportions of patients (59.3% IBD vs. 46% IBS; P=0.09). Within IBD, response was better with UC than Crohn's disease (1.86±0.13 vs. 1.26±0.11, respectively, P=0.003)., Conclusions: In a clinical practice setting, TCA use led to moderate improvement of residual gastrointestinal symptoms in IBD patients for whom escalation of IBD therapy was not planned. UC patients demonstrated higher therapeutic success. IBD symptom responses were similar to IBS patients.

Background: Indoleamine 2,3 dioxygenase-1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance-promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn's disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine., Methods: Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. The Montreal Classification was used for disease phenotyping. Disease severity was categorized by the Physician's Global Assessment. Serum tryptophan and kynurenine were measured by high-pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks., Results: In all, 25 CD patients and 11 controls were enrolled. Eight CD patients had serum collected at two different timepoints and levels of disease activity compared. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels were elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened., Conclusions: IDO1 expression in CD is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve as a reasonable objective marker of gut mucosal immune activation and as a surrogate for CD activity., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)