Changxing Ma

Type, rather than number, of mental and physical comorbidities increases the severity of symptoms in patients with irritable bowel syndrome.

BACKGROUND & AIMS Irritable bowel syndrome (IBS) has significant mental and physical comorbidities. However, little is known about the day-to-day burden these comorbidities place on quality of life (QOL), physical and mental function, distress, and symptoms of patients. METHODS We collected cross-sectional data from 175 patients with IBS, which was diagnosed on the basis of Rome III criteria (median age, 41 years; 78% women), who were referred to 2 specialty care clinics. Patients completed psychiatric interviews, a physical comorbidity checklist, the IBS Symptom Severity Scale, the IBS-QOL instrument, the Brief Symptom Inventory, the abdominal pain intensity scale, and the Short Form-12 Health Survey. RESULTS Patients with IBS reported an average of 5 comorbidities (1 mental, 4 physical). Subjects with more comorbidities reported worse QOL after adjusting for confounding variables. Multiple linear regression analyses indicated that comorbidity type was more consistently and strongly associated with illness burden indicators than disease counts. Of 10,296 possible physical-mental comorbidity pairs, 6 of the 10 most frequent dyads involved specific conditions (generalized anxiety, depression, back pain, agoraphobia, tension headache, and insomnia). These combinations were consistently associated with greater illness and symptom burdens (QOL, mental and physical function, distress, more severe symptoms of IBS, and pain). CONCLUSIONS Comorbidities are common among patients with IBS. They are associated with distress and reduced QOL. Specific comorbidities are associated with more severe symptoms of IBS.

The Irritable Bowel Syndrome Outcome Study (IBSOS): Rationale and design of a randomized, placebo-controlled trial with 12 month follow up of self- versus clinician-administered CBT for moderate to severe irritable bowel syndrome☆

Irritable bowel syndrome is a common, oftentimes disabling, gastrointestinal disorder whose full range of symptoms has no satisfactory medical or dietary treatment. One of the few empirically validated treatments includes a specific psychological therapy called cognitive behavior therapy which, if available, is typically administered over several months by trained practitioners in tertiary care settings. There is an urgent need to develop more efficient versions of CBT that require minimal professional assistance but retain the efficacy profile of clinic based CBT. The Irritable Bowel Syndrome Outcome Study (IBSOS) is a multicenter, placebo-controlled randomized trial to evaluate whether a self-administered version of CBT is, at least as efficacious as standard CBT and more efficacious than an attention control in reducing core GI symptoms of IBS and its burden (e.g. distress, quality of life impairment, etc.) in moderately to severely affected IBS patients. Additional goals are to assess, at quarterly intervals, the durability of treatment response over a 12 month period; to identify clinically useful patient characteristics associated with outcome as a way of gaining an understanding of subgroups of participants for whom CBT is most beneficial; to identify theory-based change mechanisms (active ingredients) that explain how and why CBT works; and evaluate the economic costs and benefits of CBT. Between August 2010 when IBSOS began recruiting subjects and February 2012, the IBSOS randomized 171 of 480 patients. Findings have the potential to improve the health of IBS patients, reduce its social and economic costs, conserve scarce health care resources, and inform evidence-based practice guidelines.

Fear of GI Symptoms has an Important Impact on Quality of Life in Patients With Moderate-to-Severe IBS

OBJECTIVES:Because irritable bowel syndrome (IBS) is a functional medical condition for which there is no curative therapy, treatment goals emphasize relieving gastrointestinal (GI) symptoms and optimizing the quality of life (QOL). This study sought to characterize the magnitude of the associations between QOL impairment, fear of IBS symptoms, and confounding variables.METHODS:Subjects included 234 Rome III-diagnosed IBS patients (mean age, 41 years, 79%, female) without comorbid organic GI disease who were referred to two specialty care clinics of an National Institutes of Health trial for IBS. Subjects completed a testing battery that included the IBS-specific QOL (IBS-QOL), SF-12 (generic QOL), the UCLA GI Symptom Severity Scale, the Visceral Sensitivity Index, Trait Anxiety Inventory, and Brief Symptom Inventory.RESULTS:Multiple linear regression was used to develop a model for predicting QOL. Data supported an overall model that included sociodemographic, clinical (e.g., current severity of GI symptoms), and psychosocial (e.g., fear of GI symptoms, distress, neuroticism) variables, accounting for 48.7% of the variance in IBS-QOL (F=15.1, P <0.01). GI symptom fear was the most robust predictor of IBS-QOL (β=−0.45 P <0.01), accounting for 14.4% of the total variance.CONCLUSIONS:Patients’ fear that GI symptoms have aversive consequences, is a predictor of QOL impairment that cannot be fully explained by the severity of their GI symptoms, overall emotional well-being, neurotic personality style, or other clinical features of IBS. An understanding of the unique impact that GI symptom fears have on QOL can inform treatment planning and help gastroenterologists to better manage more severe IBS patients seen in tertiary care clinics.

571 Type, Not Number, of Mental-Physical Comorbidities Increases the Severity of GI Symptoms in Patients With More Severe Irritable Bowel Syndrome

BACKGROUND: While irritable bowel syndrome (IBS) is associated with significant mental and physical comorbidity, little is known about the day to day burden (e.g., quality of life [QOL], physical and mental functioning, distress, IBS symptoms) that comorbidity imposes. METHOD: 175 Rome III-diagnosed IBS patients (M age = 41 yrs, 78% Female, 91% Caucasian) completed psychiatric assessments (MINI International Neuropsychiatric Interview), a physical comorbidity checklist as well as the IBS Symptom Severity Scale, IBSQOL, Brief Symptom Inventory (distress, BSI), abdominal pain intensity scale, and the physical (PCS) and mental (MCS) functioning scales of the SF-12 as part of baseline assessment of an NIH clinical trial. RESULTS. IBS patients in this cohort reported an avg. of 5 diagnosed comorbidities (1 mental, 4 physical). Partial correlations indicated that subjects with more comorbidities reported worse QOL after adjusting for confounding variables. The number of physical comorbidities was more strongly associated with the physical aspects of QOL, while the number of mental comorbidities was more strongly correlated with mental aspects of QOL. The number of comorbidities was unrelated to either the intensity of abdominal pain or global severity of IBS symptoms. Multiple linear regression analyses indicated that comorbidity type was more consistently and strongly associated with illness burden indicators than simple disease counts after confounding variables were held constant. Of 10, 296 possible physicalmental comorbidity pairs, 6 of the 10 most frequent dyads involved a combination of conditions (generalized anxiety disorder, major depression, back pain, agoraphobia, tension headache, insomnia) that were consistently associated with illness (QOL, mental and physical functioning, distress) and symptom (IBS symptom severity, abdominal pain intensity) burden indicators. A comorbidity dyad with consistently large effect sizes was low back pain and major depression. For these patients, scores were expected to decrease by 22 points on the IBS QOL, 10.24 on the PCS, 11.76 on the MCS, and increase by 20.61 points on the BSI in comparison to patients who are not diagnosed with MDD and LBP. For the IBS-SSS, the regression coefficient was 89.67. This means that a patient diagnosed with MDD-LBP had IBS symptom severity scores on the IBS-SSS score that, on average, are 89.67 units higher than a patient undiagnosed with MDD and LBP. CONCLUSIONS. Physical-mental comorbidity in IBS is common, associated with increased distress and QOL impairment and, for patients with specific comorbidity profiles, more severe IBS symptoms. The type of reported comorbidities, rather than their number, may be a more useful way of understanding the full scope of their impact in more severely affected IBS patients. This study was funded by NIH Grant DK77738

Su2085 The Impact of Fear of GI Symptoms on Quality of Life Impairment Due to Irritable Bowel Syndrome

G A A b st ra ct s (Kennedy et al, 2013), which may be mediated by changes in downstream neuroactive metabolites of the kynurenine pathway. Therefore, in this study we investigated if modulating tryptophan availability using acute tryptophan depletion (ATD) altered peripheral levels of kynurenine and tryptophan in patients with IBS, and if modulating these parameters impacted on measures of cognition, mood, arousal, and self-reported GI symptoms. Design: Doubleblind, placebo-controlled, crossover design. Methods: Female patients with IBS who met Rome III criteria (N = 9; mean age = 22.8 +/1.2) and age and IQ matched female healthy controls (HC; N = 14; mean age = 21.5 +/0.5) each attended two study visits, receiving the tryptophan depleting (ATD) or control (TRP+) amino acid drink on each visit. Plasma samples were collected pre and post drink, and participants completed a range of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), including the paired associates learning (PAL) test, and self report measures of GI symptoms, mood and arousal. Results: As expected, ATD reduced total plasma tryptophan, by 74.02% in healthy controls and by 85.86% in IBS patients, p < .001. In addition, ATD reduced total plasma kynurenine, by 63.12% in healthy controls and by 69.63% in IBS patients, p < .001. Following TRP+, kynurenine concentrations were significantly elevated in both IBS patients and healthy control participants, p < .001. Moreover, patients with IBS exhibited impaired visuospatial memory performance following TRP+, PAL mean errors: HC = 2.4 +/0.9, IBS = 7.8 +/1.9, p < 0.05. However, ATD eliminated this deficit. ATD had no effect on GI symptoms in patients with IBS. Conclusions: Although the peripheral changes in kynurenine following ATD are similar in patients with IBS and healthy control participants, it appears patients with IBS process tryptophan or kynurenine differentially in the central nervous system. Our results have significant implications for our understanding of the underlying pathophysiology of IBS, and suggest that targeting the kynurenine pathwaymay be a novel strategy to normalise central dysfunction in IBS. References Fitzgerald, P., et al. (2008). Neurogastroenterology & Motility, 20, 1291-1297. Kennedy, P. J., et al. (2013). Psychological Medicine, doi:10.1017/ S0033291713002171

863 What Do IBS Symptom Severity Scales Measure? GI Symptoms, Emotions, Cognitions-or Something Else?

Chirag B. Patel, Madhu Ragupathi, Nilesh Bhoot, Thomas B. Pickron, Eric M. HaasBackground: Obstructed defecation syndrome (ODS) is recognized as both a functional (e.g.,anismusoranaldyssynergia)andanatomic(e.g.,rectoceleandinternalrectalintussusception)defecatory disorder of the pelvic floor. The purpose of this study was to determine outcomesand patient satisfaction following stapled transanal rectal resection (STARR) for the surgicaltreatmentofODS.Methods:BetweenMay2006andJuly2009,1,580patientswereevaluatedfor constipation or rectocele-related symptoms. A subset with ODS was assessed with analphysiology studies and defecography. Thirty-seven of these patients were offered STARRprocedure for rectocele and internal intussusception and comprise the cohort of this study.Demographic data and surgical complications were tabulated. Long-term outcomes wereassessed by comparing pre- and post-operative subsets of the Wexner constipation scoringsystem (paired two-tailed Students t-test) as well as patient satisfaction surveys. Results: Atotal of 37 patients (100% female) with a mean age of 52.9 years (range: 31-74 years)underwent STARR procedure. All patients had clinically significant rectocele as evidencedon defecography and 82% had concomitant intussusception. Postoperative complicationsoccurred in 13 patients (35.1%) during 90-day follow-up (table). Two of these patients(5.4%) required reintervention: dilation of stricture in one and transanal excision of staplegranuloma in another. Long-term follow-up was achieved at a mean of 19.3 months (range:3-36 months) in 84% of patients. Mean pre- and post-operative constipation scores were11.1±3.6 (range: 0-17) and 4.0±3.4 (range: 0-11), respectively (p<1.3x10^-9). Overall out-come was reported as excellent or good in 71% of patients, adequate in 22.5%, and poorin 6.5%. When asked in retrospect if they would undergo the procedure again, 77%responded affirmatively. Of note, 42% of these patients experienced postoperative complica-tions. Conclusions: The STARR procedure for ODS may result in significantly improvedpatient outcomes and satisfaction. Most complications were minor and did not requirereoperative interventions. In appropriately selected patients, the STARR procedure was abeneficialoptionfortheanatomicalcorrectionofODSsecondarytorectoceleandintussuscep-tion.Surgical complications following STARR during 90-day follow up (note: some patientsexperienced more than one complication).