Psychological, physical, and sleep comorbidities and functional impairment in irritable bowel syndrome: Results from a national survey of U.S. adults.

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) in referral practice commonly report mental disorders and functional impairment. Our aim was to determine the prevalence of mental, physical and sleep-related comorbidities in a nationally representative sample of IBS patients and their impact on functional impairment. METHODS: IBS was defined by modified Rome Criteria based on responses to the chronic conditions section of the National Comorbidity Survey-Replication. Associations between IBS and mental, physical and sleep disorders and 30-day functional impairment were examined using logistic regression models. RESULTS: Of 5,650 eligible responders, 186 met criteria for IBS {weighted prevalence 2.5% (SE = 0.3)}. Age >60 years was associated with decreased odds (OR = 0.3; 95% CI:.1-.6); low family income (OR = 2.4; 95% CI:1.2-4.9) and unemployed status (OR = 2.3; 95% CI:1.2-4.2) were associated with increased odds of IBS. IBS was significantly associated with anxiety, behavior, mood disorders (ORs 1.8-2.4), but not eating or substance use disorders. Among physical conditions, IBS was associated with increased odds of headache, chronic pain, diabetes mellitus and both insomnia and hypersomnolence related symptoms (ORs 1.9-4.0). While the association between IBS and patients' role impairment persisted after adjusting for mental disorders (OR = 2.4, 95% CI 1.5-3.7), associations with impairment in self-care, cognition, and social interaction in unadjusted models (ORs 2.5-4.2) were no longer significant after adjustment for mental disorders. CONCLUSION: IBS is associated with socioeconomic disadvantage, comorbidity with mood, anxiety and sleep disorders, and role impairment. Other aspects of functional impairment appear to be moderated by presence of comorbid mental disorders.

Constipation Predominant Irritable Bowel Syndrome and Functional Constipation Are Not Discrete Disorders: A Machine Learning Approach.

INTRODUCTION: Chronic constipation is classified into 2 main syndromes, irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), on the assumption that they differ along multiple clinical characteristics and are plausibly of distinct pathophysiology. Our aim was to test this assumption by applying machine learning to a large prospective cohort of comprehensively phenotyped patients with constipation. METHODS: Demographics, validated symptom and quality of life questionnaires, clinical examination findings, stool transit, and diagnosis were collected in 768 patients with chronic constipation from a tertiary center. We used machine learning to compare the accuracy of diagnostic models for IBS-C and FC based on single differentiating features such as abdominal pain (a "unisymptomatic" model) vs multiple features encompassing a range of symptoms, examination findings and investigations (a "syndromic" model) to assess the grounds for the syndromic segregation of IBS-C and FC in a statistically formalized way. RESULTS: Unisymptomatic models of abdominal pain distinguished between IBS-C and FC cohorts near perfectly (area under the curve 0.97). Syndromic models did not significantly increase diagnostic accuracy (P > 0.15). Furthermore, syndromic models from which abdominal pain was omitted performed at chance-level (area under the curve 0.56). Statistical clustering of clinical characteristics showed no structure relatable to diagnosis, but a syndromic segregation of 18 features differentiating patients by impact of constipation on daily life. DISCUSSION: IBS-C and FC differ only about the presence of abdominal pain, arguably a self-fulfilling difference given that abdominal pain inherently distinguishes the 2 in current diagnostic criteria. This suggests that they are not distinct syndromes but a single syndrome varying along one clinical dimension. An alternative syndromic segregation is identified, which needs evaluation in community-based cohorts. These results have implications for patient recruitment into clinical trials, future disease classifications, and management guidelines.

An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS), globally affecting 11.2% of the population and imposing a direct annual cost of $1.7bn-$10bn in the US, is one of the today's major therapeutic challenges. Therefore, there is urgent need to address this issue through reviewing the tolerability and efficacy of available medications. AREAS COVERED: Over the past decade, related experiments were cited through Clinicaltrials.gov, PubMed, WHO ICTRP, and Cochrane library. Pharmacological parameters of approved medications available in the USFDA, EMA, TGA and PMDA were also stated. EXPERT OPINION: Anti-spasmodics are used as the first-line treatment in pain-predominant IBS and IBS-D, among which calcium channel blockers and neurokinin-type 2 receptor antagonists seem to replace anti-cholinergic drugs. As second-line treatments, rifaximin is considered to be the best for IBS-D though it has lower efficacy than alosetron and eluxadoline. For IBS-C, linaclotide is the most effective and the safest second-line therapy, following laxatives/fibers, which may be replaced by tenapanor, in the future. When moderate to severe IBS is associated with severe pain or comorbid psychological disorders, gut-brain neuromodulators could also be prescribed. Regarding all this, there is still a paramount need to conduct careful clinical studies on efficacy, safety and cost-effectiveness of current approved and non-approved treatments.

Global burden of irritable bowel syndrome: trends, predictions and risk factors.

Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction worldwide, defined according to patterns of gastrointestinal symptoms as described by the Rome diagnostic criteria. However, these criteria, developed with reference to research conducted largely in Western populations, might be limited in their applicability to other countries and cultures. Epidemiological data show a wide variation in the prevalence of IBS globally and more rigorous studies are needed to accurately determine any differences that might exist between countries as well as the potential explanations. The effects of IBS on the individual, in terms of their quality of life, and on health-care delivery and society, in terms of economic costs, are considerable. Although the magnitude of these effects seems to be comparable between nations, their precise nature can vary based on the existence of societal and cultural differences. The pathophysiology of IBS is complex and incompletely understood; genetics, diet and the gut microbiome are all recognized risk factors, but the part they play might be influenced by geography and culture, and hence their relative importance might vary between countries. This Review aims to provide an overview of the burden of IBS in a global context, to discuss future implications for the care of people with IBS worldwide, and to identify key areas for further research.

Effects of Irritable Bowel Syndrome on Daily Activities Vary Among Subtypes Based on Results From the IBS in America Survey.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with significant disease burden and decreased quality of life (QOL). We investigated the effects of IBS on different areas of daily function and compared these among disease subtypes. METHODS: The Life with IBS survey was conducted by Gfk Public Affairs & Corporate Communications from September through October 2015. Respondents met Rome III criteria for constipation-predominant or diarrhea-predominant IBS (IBS-C and IBS-D, respectively). Data were collected from 3254 individuals (mean age, 47 years; 81% female; and 90% Caucasian) who met IBS criteria. RESULTS: Respondents who were employed or in school (n = 1885) reported that IBS symptoms affected their productivity an average of 8.0 days out of the month and they missed approximately 1.5 days of work/school per month because of IBS. More than half the individuals reported that their symptoms were very bothersome. Individuals with IBS-C were more likely than with IBS-D to report avoiding sex, difficulty concentrating, and feeling self-conscious. Individuals with IBS-D reported more avoidance of places without bathrooms, difficulty making plans, avoiding leaving the house, and reluctance to travel. These differences remained when controlling for symptom bothersomeness, age, sex, and employment status. In exchange for 1 month of relief from IBS, more than half of the sample reported they would be willing to give up caffeine or alcohol, 40% would give up sex, 24.5% would give up cell phones, and 21.5% would give up the internet for 1 month. CONCLUSIONS: Although the perceived effects of IBS symptoms on productivity are similar among its subtypes, patients with IBS-C and IBS-D report differences in specific areas of daily function.

Therapist telephone-delivered CBT and web-based CBT compared with treatment as usual in refractory irritable bowel syndrome: the ACTIB three-arm RCT.

BACKGROUND: Irritable bowel syndrome (IBS) affects 10-22% of people in the UK. Abdominal pain, bloating and altered bowel habits affect quality of life and can lead to time off work. Current treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies, but many people suffer ongoing symptoms. Cognitive-behavioural therapy (CBT) is recommended in guidelines for patients with ongoing symptoms but its availability is limited. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of therapist telephone-delivered CBT (TCBT) and web-based CBT (WCBT) with minimal therapist support compared with treatment as usual (TAU) in refractory IBS. DESIGN: This was a three-arm randomised controlled trial. SETTING: This trial took place in UK primary and secondary care. PARTICIPANTS: Adults with refractory IBS (clinically significant symptoms for 12 months despite first-line therapies) were recruited from 74 general practices and three gastroenterology centres from May 2014 to March 2016. INTERVENTIONS: TCBT - patient CBT self-management manual, six 60-minute telephone sessions over 9 weeks and two 60-minute booster sessions at 4 and 8 months (8 hours' therapist time). WCBT - interactive, tailored web-based CBT, three 30-minute telephone sessions over 9 weeks and two 30-minute boosters at 4 and 8 months (2.5 hours' therapist time). MAIN OUTCOME MEASURES: Primary outcomes - IBS symptom severity score (IBS SSS) and Work and Social Adjustment Scale (WSAS) at 12 months. Cost-effectiveness [quality-adjusted life-years (QALYs) and health-care costs]. RESULTS: In total, 558 out of 1452 patients (38.4%) screened for eligibility were recruited - 186 were randomised to TCBT, 185 were randomised to WCBT and 187 were randomised to TAU. The mean baseline Irritable Bowel Syndrome Symptom Severity Score (IBS SSS) was 265.0. An intention-to-treat analysis with multiple imputation was carried out at 12 months; IBS SSS were 61.6 points lower in the TCBT arm [95% confidence interval (CI) 89.5 to 33.8; p < 0.001] and 35.2 points lower in the WCBT arm (95% CI 57.8 to 12.6; p = 0.002) than in the TAU arm (IBS SSS of 205.6). The mean WSAS score at 12 months was 10.8 in the TAU arm, 3.5 points lower in the TCBT arm (95% CI 5.1 to 1.9; p < 0.001) and 3.0 points lower in the WCBT arm (95% CI 4.6 to 1.3; p = 0.001). For the secondary outcomes, the Subject's Global Assessment showed an improvement in symptoms at 12 months (responders) in 84.8% of the TCBT arm compared with 41.7% of the TAU arm [odds ratio (OR) 6.1, 95% CI 2.5 to 15.0; p < 0.001] and 75.0% of the WCBT arm (OR 3.6, 95% CI 2.0 to 6.3; p < 0.001). Patient enablement was 78.3% (responders) for TCBT, 23.5% for TAU (OR 9.3, 95% CI 4.5 to 19.3; p < 0.001) and 54.8% for WCBT (OR 3.5, 95% CI 2.0 to 5.9; p < 0.001). Adverse events were similar between the trial arms. The incremental cost-effectiveness ratio (ICER) (QALY) for TCBT versus TAU was £22,284 and for WCBT versus TAU was £7724. Cost-effectiveness reduced after imputation for missing values. Qualitative findings highlighted that, in the CBT arms, there was increased capacity to cope with symptoms, negative emotions and challenges of daily life. Therapist input was important in supporting WCBT. CONCLUSIONS: In this large, rigorously conducted RCT, both CBT arms showed significant improvements in IBS outcomes compared with TAU. WCBT had lower costs per QALY than TCBT. Sustained improvements in IBS symptoms are possible at an acceptable cost. Suggested future research work is longer-term follow-up and research to translate these findings into usual clinical practice. FUTURE WORK: Longer-term follow-up and research to translate these findings into usual clinical practice is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44427879. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 23, No. 17. See the NIHR Journals Library website for further project information. The University of Southampton sponsored this study. Funding was received from the NIHR HTA Board and the NIHR Clinical Research Network and support was received from the NIHR Clinical Research Network.

Irritable bowel syndrome (IBS) is a common bowel disorder causing pain, bloating and diarrhoea or constipation, which can affect quality of life. Treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies. However, many patients suffer ongoing distressing symptoms. Guidelines recommend cognitive­behavioural therapy (CBT) for patients with ongoing IBS symptoms. However, access to therapy is limited because of cost and therapist availability. We previously developed web-based CBT (WCBT), which is more accessible, less expensive and requires less therapist time than traditional therapist telephone-delivered CBT (TCBT). The aim of the current trial was to assess the clinical effectiveness and cost-effectiveness of these two approaches. Participants were randomly assigned to TCBT, WCBT or treatment as usual (TAU). The TCBT group received a CBT manual and six 1-hour telephone CBT sessions with trained therapists over 9 weeks and two booster sessions at 4 and 8 months. The WCBT group received access to the interactive CBT website with eight online sessions at home over 9 weeks, with similar content to the therapist CBT, and received three 30-minute therapist telephone-delivered CBT sessions and two boosters at 4 and 8 months. There were 558 adults with ongoing IBS symptoms who took part from 74 general practice surgeries and three hospital clinics in London and the south of England. The main study outcomes were the IBS Symptom Severity Score and the Work and Social Adjustment Scale, which measures people's ability to function and live their lives. The results of these were collected at the start of the study and at 3, 6 and 12 months. Significant improvement in symptoms was found in the two therapy groups compared with TAU at 3, 6 and 12 months. Cost-effectiveness and wider benefits (e.g. ability to cope and mood) also showed positive results, indicating that sustained improvements in IBS symptoms are possible at an acceptable cost.

Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study.

Experimental pain sensitivity was assessed in individuals with urologic chronic pelvic pain syndrome (UCPPS) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. A series of computer-controlled pressure stimuli were delivered to the thumbnail bed, an asymptomatic site distant from the area of UCPPS pain that is considered to be indicative of overall body pain threshold. Stimuli were rated according to a standardized magnitude estimation protocol. Pain sensitivity in participants with UCPPS was compared with healthy controls and a mixed pain group composed of individuals with other chronic overlapping pain conditions, including fibromyalgia, chronic fatigue, and irritable bowel syndromes. Data from 6 participating MAPP testing sites were pooled for analysis. Participants with UCPPS (n = 153) exhibited an intermediate pain sensitivity phenotype: they were less sensitive relative to the mixed pain group (n = 35) but significantly more sensitive than healthy controls (n = 100). Increased pain sensitivity in patients with UCPPS was associated with both higher levels of clinical pain severity and more painful body areas outside the pelvic region. Exploratory analyses in participants with UCPPS revealed that pain sensitivity increased during periods of urologic symptom flare and that less pressure pain sensitivity at baseline was associated with a greater likelihood of subsequent genitourinary pain improvement 1 year later. The finding that individuals with UCPPS demonstrate nonpelvic pain hypersensitivity that is related to clinical symptoms suggests that central nervous system mechanisms of pain amplification contribute to UCPPS.

Value-based Pricing for Rifaximin Increases Access of Patients With Irritable Bowel Syndrome With Diarrhea to Therapy.

BACKGROUND & AIMS: Increasing drug prices lead to payer coverage restrictions, which limit access to therapy. We assessed the cost effectiveness of rifaximin in management of patients with irritable bowel syndrome with diarrhea (IBS-D) under common payer coverage restrictions and determined the maximum price at which rifaximin would be cost effective using contemporary cost-effectiveness thresholds. METHODS: A decision analytic model was constructed to evaluate quality of life, cost, and cost effectiveness of rifaximin for patients with IBS-D and complete noncoverage (insurer pays none of the drug cost), unrestricted access (insurer pays 100% of the drug cost), and formulary-restricted access (insurer pays 100% of the drug cost after for patients failed by initial therapy). The maximum cost-effective drug price was determined for each level of drug coverage using threshold analysis adjusted for willingness to pay thresholds from $50,000 to $150,000 per quality-adjusted life year (QALY). Analysis was performed from a payer perspective with a 1-year time horizon. RESULTS: Unrestricted and formulary-restricted access were more effective than complete non-coverage, resulting in additional 0.03 and 0.05 QALYs gained over noncoverage. However, unrestricted and formulary-restricted coverage were more expensive. At current drug prices, unrestricted or formulary-restricted coverage would cost an additional $1,207,136 or $171,850/QALY gained, compared to complete non-coverage. A 12% to 62% price reduction ($18.46 to $26.34/pill) for formulary-restricted access and 84% to 88% price reduction ($3.53 to $4.71/pill) for unrestricted access would be needed for rifaximin to be a cost-effective treatment strategy. Rifaximin retreatment intervals, response rates, and adverse events were important factors in sensitivity analysis. CONCLUSION: Using a decision analytic model, we show that payer coverage for rifaximin for patients with IBS-D exceeds generally accepted cost-effectiveness thresholds at current drug prices. Improved payer coverage could be justified using value-based pricing methods.

The complex interplay between gastrointestinal and psychiatric symptoms in irritable bowel syndrome: A longitudinal assessment.

AIMS: The aims of this study were to better define the relationship between irritable bowel syndrome (IBS) and psychiatric disorders and to examine the efficacy of paroxetine in the treatment of IBS patients. METHODS: One hundred fifty subjects with diagnosis of IBS (Roma III criteria) and relative sub-classification (constipated, diarrhea, and mixed) were assessed for psychopathological features and gastrointestinal symptoms using IBS Symptom Severity Score and were consecutively enrolled. Fifty patients assumed paroxetine for 16 weeks and were longitudinally evaluated. RESULTS: The entire sample had a moderate/severe gastrointestinal symptomatology (IBS-SSS 285.1 ± 98.6). The IBS subtypes were diarrhea (47.3%), constipated (32%), and mixed (20.7%). Panic disorder was found in 17.4% and major depressive episode in 14.7%. More than 50% of the patients showed "psychopathological features." This group showed more severe gastrointestinal symptoms and worse quality of life than the group without any psychiatric comorbidity (44%). Psychiatric patients also showed a significant impairment of physical state, subjective feeling of well-being, and leisure activities when compared with no psychiatric patients. When the IBS-SSS > 300 group was subgrouped in psychiatric (67.2%) and no psychiatric (32.8%), we found significant differences in all clinician-administered and self-reported scales with more severe psychopathological features in psychiatric group (P < 0.01). Among the patients treated with paroxetine, 34 (68%) completed the longitudinal evaluation showing a significant improvement of both psychiatric and gastrointestinal symptoms. CONCLUSIONS: This study confirms a high presence of psychiatric comorbidities, emphasizing the need for psychiatric screening in all patients with IBS; moreover, the longitudinal evaluation of patients treated with paroxetine showed a significant improvement of both psychiatric and gastrointestinal symptoms.

The evolution of magnetic resonance enterography in the assessment of motility disorders in children.

Gastrointestinal symptoms including constipation, diarrhoea, pain and bloating represent some of the most common clinical problems for patients. These symptoms can often be managed with cheap, widely available medication or will spontaneously resolve. However, for many patients, chronic GI symptoms persist and frequently come to dominate their lives. At one end of the spectrum there is Inflammatory Bowel Disease (IBD) with a clearly defined but expensive treatment pathway. Contrasting with this is Irritable Bowel Syndrome (IBS), likely a collection of pathologies, has a poorly standardised pathway with unsatisfactory clinical outcomes. Managing GI symptoms in adult populations is a challenge. The clinical burden of gastrointestinal disease is also prevalent in paediatric populations and perhaps even harder to treat. In this review we explore some of the recent advances in magnetic resonance imaging (MRI) to study the gastrointestinal tract. Complex in both its anatomical structure and its physiology we are likely missing key physiological markers of disease through relying on symptomatic descriptors of gut function. Using MRI we might be able to characterise previously opaque processes, such as non-propulsive contractility, that could lead to changes in how we understand even common symptoms like constipation. This review explores recent advances in the field in adult populations and examines how this safe, objective and increasingly available modality might be applied to paediatric populations.

Better Understanding and Recognition of the Disconnects, Experiences, and Needs of Patients with Irritable Bowel Syndrome with Constipation (BURDEN IBS-C) Study: Results of an Online Questionnaire.

INTRODUCTION: The BURDEN IBS-C study was conducted to better understand the experiences, attitudes, and unmet needs of sufferers of irritable bowel syndrome with constipation (IBS-C) in comparison to the perceptions and challenges of healthcare providers (HCPs) who treat IBS-C patients. METHODS: This was an author-developed, online questionnaire using KnowledgePanel® to survey individuals with IBS-C (N = 1311). HCPs participated in a complementary online questionnaire and were recruited separately (N = 331). The study was fielded from June 29, 2016, to January 30, 2017. RESULTS: Most patients had used (86%) and/or were using (76%) over-the-counter treatments for their IBS-C, with 12% currently on prescription therapy. At the time this study was conducted, 66% and 63% were not satisfied/completely satisfied with over-the-counter or prescription treatment, respectively, citing inadequate efficacy (55%) and side effects (39%), most commonly diarrhea, as common reasons for dissatisfaction. IBS-C respondents most commonly reported feeling frustrated (43%) and stressed (28%) regarding IBS-C, though 39% were accepting of IBS-C as part of daily life. HCPs were aligned with patients in thinking that patients were frustrated (76%) and stressed (65%) but HCPs were less likely to recognize that patients had become accepting of their IBS-C (13%). Most HCPs (79%) were not satisfied/completely satisfied with the prescription treatments available at the time this study was conducted. Inadequate response rates to current therapies (55%) and treatment adherence/compliance issues (58%) were the most frequent challenges encountered by HCPs. IBS-C respondents reported that their symptoms impacted productivity and personal activity, on average, 4 and 3 days/month, respectively. CONCLUSION: These results suggest that current management pathways may not be adequately addressing the symptoms and needs of individuals with IBS-C, most notably side effects and lack of efficacy. Patients and HCPs expressed dissatisfaction with over-the-counter and prescription treatments available at the time this study was conducted. Additional treatment options and improved dialogue would be beneficial to HCPs and patients. FUNDING: Synergy Pharmaceuticals Inc.

Assessment of the effectiveness and safety of ethosuximide in the treatment of abdominal pain related to irritable bowel syndrome - IBSET: protocol of a randomised, parallel, controlled, double-blind and multicentre trial.

INTRODUCTION: Irritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease. This is the first reason for consultation in gastroenterology, with an estimated prevalence of 10%-15% in industrialised countries. Although this is a benign gastrointestinal disease, its chronicity profoundly impacts the patient's quality of life and causes considerable health spending. Actual medical treatments are poorly efficient on IBS-related abdominal pain, making it a major public health concern. The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS. METHODS AND ANALYSIS: The IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating the efficacy and safety of ethosuximide on abdominal pain related to IBS. Adults with IBS that report significant abdominal pain (≥4/10) at least for 3 months will be included. 290 patients will be randomly assigned to receive either ethosuximide or placebo over 12 weeks after 1 week of run-in period. The primary endpoint is the rate of responders (pain reduction ≥30% and Subject Global Assessment of Relief score ≥4). The intensity of abdominal pain will be assessed by an 11-point Numerical Rating Scale before and after 12 weeks of treatment and the score of the Subject Global Assessment of Relief scale at the end of treatment. The secondary endpoints are the safety of ethosuximide, the intensity and features of IBS and quality of life. ETHICS AND DISSEMINATION: The study was approved by an independent medical ethics committee (CPP Sud-Est VI, Clermont-Ferrand, France). The results will be published in a peer-review journal and presented at international congresses. TRIAL REGISTRATION NUMBER: NCT02973542; Pre-results.

Development of the Diary for Irritable Bowel Syndrome Symptoms to Assess Treatment Benefit in Clinical Trials: Foundational Qualitative Research.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and alterations in bowel habits. Three subtypes are defined on the basis of stool patterns: diarrhea-predominant IBS, constipation-predominant IBS, and alternating or mixed IBS. OBJECTIVES: To develop patient-reported outcome measures for qualification by the Food and Drug Administration to support product approvals and labeling in IBS; the article focuses on the qualitative research that provided the foundation for the new measures. METHODS: Forty-nine concept elicitation and 42 cognitive debriefing interviews were conducted with subjects meeting Rome III criteria; additional criteria were imposed to yield a sample representative of the target patient population. RESULTS: Although incomplete bowel movements, abnormal stool frequency and consistency, and abdominal pain, discomfort, and bloating were reported most frequently across concept elicitation interviews, the relative importance of specific symptoms varied by subtype. Among their five symptoms most important to treat, diarrhea-predominant and alternating or mixed IBS subjects frequently identified urgency, loose/watery stools, abdominal pain, and cramping, whereas constipation-predominant IBS subjects commonly included infrequent and incomplete bowel movements, bloating, and abdominal pain. The cognitive debriefing interviews facilitated refinement of each item set, supported minor modifications following translatability assessment, and suggested improvements to the electronic interface. Furthermore, subjects reported that every item was relevant and no concepts of importance were missing. CONCLUSIONS: Results support the content validity of the IBS patient-reported outcome measures. A pilot study was recently initiated to inform item reduction, develop scoring algorithms, and provide preliminary psychometric information. Comprehensive psychometric evaluation and responder definition development will follow.

Sex-Related Differences in GI Disorders.

Epidemiological studies indicate sex-related differences among functional gastrointestinal disorders (FGIDs) wherein females are more likely to receive a diagnosis than their male counterparts. However, the mechanism by which females exhibit an increased vulnerability for development of these pathophysiologies remains largely unknown, and therapeutic treatments are limited. The current chapter focuses on clinical research outlining our current knowledge of factors that contribute to the female predominance among FGID patients such as the menstrual cycle and sex hormones. In addition, we will discuss progress in preclinical research, including animal models, which serve as valuable tools for the investigation of the development and long term manifestation of symptoms observed within the patient population. Although much progress has been made, additional longitudinal studies in both clinical and preclinical research are necessary to identify more specific mechanisms underlying sex-related differences in FGIDs as well as targets for improved therapeutic approaches.

Use of Rome criteria for the diagnosis of irritable bowel syndrome in primary care: a survey among European countries.

BACKGROUND AND OBJECTIVES: The majority of patients with irritable bowel syndrome (IBS) are diagnosed and treated in primary care. The aim of this study was to investigate the implementation of the Rome criteria in daily primary care clinical practice and adherence of general practitioners (GPs) to recommended diagnostic approaches for IBS. PATIENTS AND METHODS: A survey consisting of 18 questions was distributed across 11 European countries and was used to assess GPs' diagnostic approach of IBS, the use of Rome criteria in daily practice and GPs' perspective on the aetiology of the disorder. RESULTS: Overall, 185 GPs completed the survey. In daily clinical practice, 32% of GPs reported that they usually make a positive diagnosis on the basis of symptoms only, whereas 36% of GPs reported regular use of the Rome criteria to diagnose IBS. Furthermore, 62% of the responders reported that they applied additional diagnostics, such as blood tests, 31% found it necessary to perform endoscopy to make a positive diagnosis of IBS and 29% referred patients with IBS to a specialist. Psychological factors were the most frequently selected potential aetiological factor of IBS (88% of GPs). Overall, 52% of GPs reported systematically including questions on psychological symptoms in the assessment of history of IBS. CONCLUSION: Only about one-third of GPs regularly used the Rome criteria to diagnose IBS. In daily primary care practice, IBS largely remains a diagnosis of exclusion. This has implications in terms of GPs' specialty training and questions the applicability of IBS guidelines in daily care, which advocate an early, positive, symptom-based diagnosis.

Psychological Interventions for Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) patients often present psychoform symptoms or psychiatric disorders. Among the psychological factors studied in IBS patients, two seem to influence mostly its severity: catastrophizing and somatization. Somatization is an independent risk factor for IBS. In addition, somatization more than the severity of IBS influences the way the patients perceive their illness, the outcome and the efficacy of treatment. Irritable bowel syndrome patients demonstrate greater catastrophizing scores than controls, and pain catastrophizing is a significant predictor of gastrointestinal symptoms related to pain. In this context we analysed the data regarding the efficacy of two psychological treatments in IBS: cognitive behavioral therapy and hypnosis. Cognitive behavioral therapy is focused on replacing maladaptive coping strategies with more positive cognitions and behaviors. Several studies showed that cognitive behavioral therapy is effective in reducing bowel symptoms in IBS, both post-treatment and short-term follow-up. Gut-directed hypnotherapy has beneficial short-term effects in improving gastrointestinal symptoms of patients with IBS, and the results are maintained after one year in half of the patients. Psychological treatments are a suitable option for selected IBS patients.

Food, fibre, bile acids and the pelvic floor: An integrated low risk low cost approach to managing irritable bowel syndrome.

Patients presenting with abdominal pain and diarrhea are often labelled as suffering from irritable bowel syndrome, and medications may be used often without success. Advances in the understanding of the causes of the symptoms (including pelvic floor weakness and incontinence, bile salt malabsorption and food intolerance) mean that effective, safe and well tolerated treatments are now available.

Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation.

AIM: To determine effect of irritable bowel syndrome (IBS) subtype on IBS-specific quality of life (QOL) questionnaire and its subscales. METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States. IBS and IBS subtype were diagnosed using Rome-III questionnaire. QOL was assessed using IBS-QOL questionnaire. IBS-QOL assesses quality of life along eight subscales: dysphoria, interference with activities, body image, health worry, food avoidance, social reactions, sexual health, and effect on relationships. IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL. Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI. We compared mean IBS-QOL score and its subscales among various IBS-subtypes. Analysis of variance (ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender. A post-hoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05. RESULTS: Of 542 patients screened, 243 had IBS as per Rome-III criteria. IBS-mixed (IBS-M) was the most common IBS subtype (121 patients, 49.8%) followed by IBS- diarrhea (IBS-D) (56 patients, 23.1%), IBS-constipation (IBS-C) (54 patients, 22.2%) and IBS-unspecified (IBS-U) (12 patients, 4.9%). Overall IBS-QOL scores were significantly different among various IBS-subtypes (P = 0.01). IBS-QOL of patients with IBS-D (61.6, 95%CI: 54.0-69.1) and IBS-M (63.0, 95%CI: 58.1-68.0) was significantly lower than patients with IBS-C (74.5, 95%CI: 66.9-82.1) (P = 0.03 and 0.02 respectively). IBS-D patients scored significantly lower than IBS-C on food avoidance (45.0, 95%CI: 34.8-55.2 vs 61.1, 95%CI: 50.8-71.3, P = 0.04) and interference with activity (59.6, 95%CI: 51.4-67.7 vs 82.3, 95%CI: 74.1-90.6, P < 0.001). IBS-M patients had more interference in their activities (61.6, 95%CI: 56.3-66.9 vs 82.3, 95%CI: 74.1-90.6, P = 0.001) and greater impact on their relationships (73.3, 95%CI: 68.4-78.2 vs 84.7, 95%CI: 77.2-92.2, P = 0.02) than IBS-C patients. Patients with IBS-M also scored significantly lower than IBS-C on food avoidance (47.2, 95%CI: 40.7-53.7 vs 61.1, 95%CI: 50.8-71.3, P = 0.04) and social reaction (66.1, 95%CI: 61.1-71.1 vs 80.0, 95%CI: 72.1-87.7, P = 0.005). CONCLUSION: IBS-D and IBS-M patients have lower IBS-QOL than IBS-C patients. Clinicians should recognize food avoidance, effects on daily activities and relationship problems in these patients.