Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics.

BACKGROUND: Serum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. METHODS: Serum levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. KEY RESULTS: Irritable bowel syndrome patients (n = 246) had higher serum levels of IL-1ß, IL-6, IL-8, TNF, and IL-10 compared to HS (n = 21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. CONCLUSIONS & INFERENCES: Serum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS.

Curriculum for neurogastroenterology and motility training: A report from the joint ANMS-ESNM task force.

Although neurogastroenterology and motility (NGM) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency-based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society (ANMS) and the European Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM, consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro-esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy (surgery, endoscopic intervention, medications, other therapy), and transition of pediatric patients into adult practice. A 3-tiered training curriculum covering these domains is proposed here and endorsed by all NGM societies. Tier 1 NGM knowledge and training is expected of all gastroenterology trainees and practicing gastroenterologists. Tier 2 knowledge and training is appropriate for trainees who anticipate NGM disorder management and NGM function test interpretation being an important part of their careers, which may require competency assessment and credentialing of test interpretation skills. Tier 3 knowledge and training is undertaken by trainees interested in a dedicated NGM career and may be restricted to specific domains within the broad NGM field. The joint ANMS and ESNM task force anticipates that the NGM curriculum will streamline NGM training in North America and Europe and will lead to better identification of centers of excellence where Tier 2 and Tier 3 training can be accomplished.

Development and validation of a childhood self-efficacy for functional constipation questionnaire.

BACKGROUND: Children with functional constipation fear painful bowel movements leading to stool withholding behavior. Self-efficacy is the belief that an individual can accomplish a given goal. If children with constipation avoid defecation because they think that they are unable defecate comfortably, this low self-efficacy may prevent treatment success. The aim of the current study was to develop and validate a constipation specific self-efficacy scale. METHODS: The self-efficacy for functional constipation questionnaire (SEFCQ) was developed by the authors and evaluated by 10 children and seven experts. Ninety-nine healthy children and 122 children with functional constipation completed the SEFCQ and three other questionnaires measuring related constructs. KEY RESULTS: Minor changes were made in wording based on feedback from experts and children. Factor analysis showed two scales, a 7 item Action scale (Cronbach's α = 0.88) and a 7 item Emotion scale (Cronbach α = 0.86). The SEFCQ total scale correlated positively with general self-efficacy (r = .32, P < .001) and quality of life (r = .20; P < .01) and negatively with anxiety (r = -.15; P < .05). Scores on the SEFCQ were higher in children without functional constipation compared to those with functional constipation (53.33 + 3.38 vs 39.34 + 7.19, P < .001). CONCLUSIONS & INFERENCES: We developed a constipation specific self-efficacy questionnaire with good initial internal reliability, excellent face validity and adequate content validity. A low self-efficacy for defecation, may make the child resist their physical urge to defecate and hence, the need for further studies to assess its effect on treatment outcomes.

Recommendations for pharmacological clinical trials in children with irritable bowel syndrome: the Rome foundation pediatric subcommittee on clinical trials.

BACKGROUND: There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies. PURPOSE: In order to address these issues the Rome Foundation and members of the Pediatric Committee of the European Medicines Agency formed a subcommittee on clinical trials to develop guidelines for the design of clinical trials in children with irritable bowel syndrome (IBS). The following recommendations are based on evidence from published data when available and expert opinion. KEY RECOMMENDATIONS: The subcommittee recommends randomized, double-blind, placebo-controlled, parallel-group, clinical trials to assess the efficacy of new drugs. The combined endpoints for abdominal pain are a decrease in intensity of at least 30% compared with baseline and to meet or exceed the Reliable Change Index (RCI) for the sample. Stool consistency is measured with the Bristol Stool Scale Form (BSFS). The subcommittee recommends as entry criteria for abdominal pain a weekly average of worst abdominal pain in past 24 h of at least 3.0 on a 0-10 point scale or at least 30 mm in 100 mm Visual Analog Scale. For stool endpoints the committee recommends an average stool consistency lower than 3 in the BSFS during the run-in period for clinical trials on IBS-C and an average stool consistency greater than 5 in the BSFS during the run-in period for clinical trials on IBS-D. Changes in stool consistency are the primary endpoints for both IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C).

Adolescents with irritable bowel syndrome report increased eating-associated symptoms, changes in dietary composition, and altered eating behaviors: a pilot comparison study to healthy adolescents.

BACKGROUND: About half of adult irritable bowel syndrome (IBS) patients report symptoms with eating and disordered eating habits. However, little is known about eating in adolescent IBS patients, a common age at which eating disorders develop. The aim of the study was to investigate if adolescents with IBS are more likely than healthy controls (HCs) to experience eating-associated symptoms (EAS), report disordered eating patterns, and show differences in diet composition. METHODS: A total of 99 adolescents between 15 and 21 years-of-age participated (n = 48 IBS; n = 51 HCs). All subjects completed three 24-h dietary recalls and questionnaires on EAS and disordered eating. KEY RESULTS: IBS patients were more likely to report EASs than HC (91.7% vs 28%, p < 0.001). Eating-associated symptoms were controlled by avoiding the offending food (97.7%), not eating any food even when hungry (43.2%), or vomiting after eating (13.6%). Compared to HC, IBS patients reported reduced daily intake of overall calories (1828 vs 2139; p < 0.05), fat (65.4 g vs 81.4 g, p < 0.05), and lactose (8.2 g vs 12.8 g, p < 0.01). No differences were found between IBS and HC in screening for disordered eating patterns or BMI, though IBS patients endorsed using potentially unhealthy eating behaviors in an attempt to control symptoms. CONCLUSIONS & INFERENCES: Eating-associated symptoms are very common in adolescents with IBS and associated with changes in eating behaviors and dietary composition. They do not appear to change BMI and risk for eating disorders. More research is needed to guide adolescents with IBS in making appropriate dietary changes to control EASs.

Motility response to colonic distention is increased in postinfectious irritable bowel syndrome (PI-IBS).

BACKGROUND: Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether postinfectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone, and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC). METHODS: Two hundred and eighteen Rome III-positive IBS patients and 43 HC participated. IBS patients were designated PI-IBS, if their IBS symptoms began following an episode of gastroenteritis characterized by two or more of: fever, vomiting, or diarrhea. Pain threshold to phasic distentions of the descending colon was assessed using a barostat. Colonic motility was assessed with the barostat bag minimally inflated to the individual operating pressure (IOP), at 20 mmHg above the IOP, and following a test meal. IBS symptom severity and psychological symptoms were assessed by the IBS Severity Scale (IBS-SS) and the Brief Symptom Inventory-18 (BSI-18). KEY RESULTS: Twenty two (10.1%) met criteria for PI-IBS. Both IBS and HC groups showed a significant increase in motility index during intraluminal distention and following meals. The magnitude of the response to distention above (orad to) the balloon was significantly greater in PI-IBS compared with NI-IBS (p < 0.05) or HC (p < 0.01). Differences between PI-IBS and NI-IBS were not significant for IBS symptom severity, pain threshold, barostat bag volumes, or any psychological score on the BSI-18. CONCLUSIONS & INFERENCES: Patients with PI-IBS have greater colonic hypercontractility than NI-IBS. We speculate that sustained mild mucosal inflammation may cause this colonic irritability.

Test of the child/adolescent Rome III criteria: agreement with physician diagnosis and daily symptoms.

BACKGROUND: Establishment of the Rome criteria advanced diagnosis of children with Functional Gastrointestinal Disorders. The criteria were overhauled in 2006, but these revisions were never systematically tested. The aim of the current study was to assess psychometric properties of the childhood Rome III criteria and determine how well they agree with physician diagnoses and daily symptoms. METHODS: A total of N = 135 families from two pediatric gastroenterology clinics completed the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS- RIII). Half of the families completed the QPGS-RIII again in 2 weeks, the other half completed 2-week daily diaries. Children above the age of 10 also provided data (N = 64). Physician diagnoses were obtained from the medical records. KEY RESULTS: Diagnoses: The most common diagnoses per child/parent report were Irritable Bowel Syndrome (IBS; 43-47%) and Abdominal Migraine (26-36%). The most frequent physician diagnoses were Functional Constipation (FC; 53%) and Functional Abdominal Pain (FAP; 29%). Reliability: Moderate to substantial agreement was found between baseline and 2-week follow-up for most diagnoses (kappa = .19-.78) and between parent and child reports (kappa = -.04-.64). VALIDITY: There was low agreement between QPGS-RIII and physician diagnosis (kappa =-.02-.34) as well as diaries (kappa = .06-30). CONCLUSIONS & INFERENCES: The Rome criteria have reasonable test-retest reliability and seem to be inclusive, as the majority of children obtain a diagnosis. However, validity is still an issue: The Rome criteria do not overlap well with physician diagnosis or daily symptoms. These issues will need to be addressed in future revisions of the Rome criteria.

The clinical approach to chronic abdominal pain and irritable bowel syndrome in children.

Chronic recurrent abdominal pain is a common complaint evaluated by pediatricians, and a cause of concern for children and parents. Population and school based studies have reported that approximately 8% of children experience chronic abdominal pain. About half of these children will contact a physician about their pain. These children report reduced quality of life and interferences with school and play due to their pain. The large majority of children will not have a readily identified cause for their symptoms, and chronic abdominal pain is frequently classified as a functional gastrointestinal disorder (FGID). The below case study illustrates the presentation, evaluation, and clinical management of a child with chronic abdominal pain.

Self-reported crying during the menstrual cycle: sign of discomfort and emotional turmoil or erroneous beliefs?

Crying is generally associated with distress and discomfort, and is also part of the premenstrual syndrome in women. The present studies focussed on crying fluctuations during the menstrual cycle. First, a retrospective cross-cultural study of women from 33 different countries (n = 2447) was conducted. Crying proneness reportedly increased before menstruation, with remarkable cross-cultural differences. Women who were using oral contraceptives (OC) reported largely the same pattern of results as women who were not using OC. In a second study, 82 Dutch students kept a crying and mood diary for two consecutive menstrual cycles. During no phase of the menstrual cycle did actual crying episodes or crying proneness increase, although significant changes in mood were reported. Given the large cross-cultural differences on the one hand, and the remarkable correspondence between the self-reports of those using OC and those who did not use them on the other, it is concluded that the role of female sex hormone fluctuations in crying has to be questioned. Rather, it seems more likely that fluctuations in self-reported crying are based on implicit theories about the relationship between the menstrual cycle, mood and crying.