Background/Aims

Functional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system.

Methods

Serum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera.

Results

Eighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa.

Conclusions

Results of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies.

Irritable bowel syndrome (IBS) is a common chronic disorder seen in gastroenterology and primary care practice. It is characterized by recurrent abdominal pain or discomfort associated with disturbed bowel function. It is a heterogeneous disorder with varying treatments, and in this regard physicians sometimes struggle with finding the optimal approach to management of patients with IBS. This disorder induces high health care costs and variably reduces health-related quality of life. IBS is in the class of functional gastrointestinal disorders, and results from dysregulation of central and enteric nervous system interactions. Psychosocial factors are closely related to their gut physiology, associated cognitions, symptom manifestations and illness behavior. Therefore, it is important for the physician to recognize the psychosocial issues of patients with IBS and in addition to build a good patient-physician relationship in order to optimize treatment. This review focuses on the interaction between psychological and physiological factors associated with IBS by using a biopsychosocial model. In this article, we describe (1) the predisposing psychological features seen in early life; (2) the psychological factors associated with life stress, the symptom presentation, and their associated coping patterns; (3) gut pathophysiology with emphasis on disturbances in motility, visceral hypersensitivity and brain-gut interactions; and finally (4) the clinical outcomes and effective treatments including psychotherapeutic methods.

Objective

The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors.

Methods

Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30 mm Hg vs 34 mm Hg distensions; psychological influences were measured by the report criterion—that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI).

Results

IBS patients had lower AML pain thresholds (median: 28 mm Hg vs 40 mm Hg; p<0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p = 0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 (“mild” pain) vs 5.2 (“weak” pain); p = 0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r = −0.13; p = 0.14), but were strongly correlated with report criterion (r = 0.67; p<0.0001). Report criterion was inversely correlated with BSI somatisation (r = −0.26; p = 0.001) and BSI global score (r = −0.18; p = 0.035). Similar results were seen for the non‐painful sensation of urgency.

Conclusion

Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.

Background

While clinicians generally make treatment decisions in IBS related to the type of symptoms, other factors such as the perceived severity and the risks patients are willing to tolerate for effective treatment are also important to consider. These factors are not fully understood.

Objective

To describe among patients with IBS their symptoms and severity, quality of life and health status, medications taken, and the risk that they would take to continue medications for optimal relief.

Methods

Adult patients diagnosed with IBS who accessed the websites of the International Foundation for Functional GI Disorders (IFFGD) or the UNC Center for Functional GI Disorders filled out questionnaires to address the study aims.

Results

The 1,966 respondents (83% female, 91% Caucasian, 78% USA/Canada) reported impaired health status: restricting on average 73 days of activity in a year, having poor HRQOL particularly with dietary restrictions, mood disturbance and interference with daily activity, and 35% reported their symptoms as severe defined primarily as pain, bowel difficulties, bloating and eating/dietary restrictions). These symptoms were reported in some combination by over 90%, and 35.1% endorsed all 4 items. To receive a treatment that would make them symptom free, patients would give up 25% of their remaining life (average 15 years) and 14% would risk a 1/1000 chance of death. Most of the medications being taken were for pain relief and 18% were taking narcotics. Complementary and alternative treatments were used by 37%.

Conclusions

Patients accessing IBS informational websites report moderate to severe impairments in health status, and would take considerable risk to obtain symptom benefit. There is an unmet need to find effective treatments for patients with IBS and regulatory agencies might consider raising risk-benefit ratios when approving new medications for IBS.

Background & Aims

Patients with diarrhea-predominant IBS (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This is the first study to prospectively evaluate a VLCD in IBS-D.

Methods

Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 grams of carbohydrates/day). A responder was defined as having adequate relief (AR) of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life (QOL) were also measured.

Results

Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting AR for all 4 VLCD weeks. Stool frequency decreased (2.6 ± 0.8/day to 1.4 ± 0.6/day; p<0.001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score: 5.3 ± 0.7 to 3.8 ± 1.2; p<0.001). Pain scores and QOL measures significantly improved. Outcomes were independent of weight loss.

Conclusion

A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.

Objectives

Patients with functional gastrointestinal (GI) disorders treated with tricyclic antidepressants may report non-GI symptoms. It is unclear whether these symptoms are side effects of the medication or reflect a general behavioral tendency to report symptoms. This study 1) evaluated whether a checklist of symptoms reported by patients prior to taking desipramine increased in number or worsened in severity after being on a tricyclic antidepressant (desipramine), and 2) assessed baseline factors that predispose patients to report symptoms.

Methods

Female patients in the drug arm of a multi-center NIH treatment trial for functional bowel disorders completed a 15 item symptom questionnaire at baseline before randomization and at 2 weeks after starting Desipramine (n=81), or placebo (n=40) and at study completion 12 weeks later. Patients were asked on each occasion if they experienced any of 15 Symptoms and its level of severity and frequency, and the results were compared.

Results

A total of 57 patients in the desipramine arm who completed the questionnaire at both week 0 and week 2 comprised the study sample. Certain symptoms reported as side effects: dizziness, dry mouth/thirstiness, lightheadedness, feeling jittery or tremors and flushing not only were reported more often but also worsened at week 2 indicating a drug effect. Conversely, other symptoms that were also reported as side effects: feeling tired in AM, nausea, blurred vision, headaches, decreased appetite, and trouble sleeping either did not change in severity or showed improvement at week 2 (tiredness). All these symptoms except trouble sleeping were reported less often at Week 2 than at baseline (Week 2). Psychological distress but not desipramine level significantly correlated with symptom reporting.

Conclusions

The majority of symptoms often attributed to side effects of desipramine were present prior to treatment, and only a few related to its anticholinergic effects worsened 2 weeks after beginning treatment, suggesting that most symptoms considered as side effects were not related to drug per se. Clinicians should consider that “Side effects” may relate more to psychological distress than to drug effects.

Background

Adequate relief of IBS symptoms (IBS-AR) has been used as a primary endpoint in many randomized controlled trials of IBS and is considered by the Rome III Committee to be an acceptable primary endpoint. However, controversy exists on whether baseline severity confounds the effect of this treatment patient outcome.

Aims

In a randomized controlled treatment trial (1) to compare subjective report of IBS-AR to global assessment of improvement (IBS-GAI), change in IBS symptom severity scale (IBS-SSS) and IBS Quality of Life (IBS-QOL); (2) to explore whether initial IBS symptom severity influences the sensitivity of these outcome measures; (3) to determine whether psychological symptoms influence the sensitivity of these measures.

Methods

289 adult IBS patients were recruited to a treatment trial. Baseline IBS-SSS scores were used to classify IBS severity as mild (<150), moderate (150-300), or severe (>300). Questionnaires were completed at baseline and after 3 weeks of treatment with sham acupuncture or waitlist control.

Results

IBS baseline severity significantly affected the proportion of patients who reported IBS-AR at 3 weeks (mild, 70%; moderate, 49.7%; severe, 38.8%) (p<0.05). However, once the patients who reported IBS-AR at baseline (28.0%) were excluded from the analysis, baseline severity no longer affected the proportion of patients reporting IBS-AR. Baseline severity did not have a significant of effect patients reporting moderate or significant improvement on the IBS-GAI (mild, 30%; moderate, 25.3%; severe, 18.8%) (p=NS). Psychological symptoms had no significant correlations with responders after adjusting for baseline severity.

Conclusions

These data suggest that IBS-AR as an endpoint is confounded with initial IBS symptom severity as measured by baseline reporting of adequate relief. The confounding effects of adequate relief can be eliminated if patients who report adequate relief at screening are excluded from study participation.

Background

Functional Bowel Disorders (FBD) are chronic disorders that are difficult to treat and manage. Many patients and doctors are dissatisfied with the level of improvement in symptoms that can be achieved with standard medical care which may lead them to seek alternatives for care. There are currently no data on the types of Complementary and Alternative Medicine (CAM) used for FBDs other than Irritable Bowel Syndrome (IBS), or on the economic costs of CAM treatments. The aim of this study is to determine prevalence, types and costs of CAM in IBS, functional diarrhea, functional constipation, and functional abdominal pain.

Methods

1012 Patients with FBD were recruited through a health care maintenance organization and followed for 6 months. Questionnaires were used to ascertain: Utilization and expenditures on CAM, symptom severity (IBS-SS), quality of life (IBS-QoL), psychological distress (BSI) and perceived treatment effectiveness. Costs for conventional medical care were extracted from administrative claims.

Results

CAM was used by 35% of patients, at a median yearly cost of $200. The most common CAM types were ginger, massage therapy and yoga. CAM use was associated with female gender, higher education, and anxiety. Satisfaction with physician care and perceived effectiveness of prescription medication were not associated with CAM use. Physician referral to a CAM provider was uncommon but the majority of patients receiving this recommendation followed their physician's advice.

Conclusion

CAM is used by one-third of FBD patients. CAM use does not seem to be driven by dissatisfaction with conventional care. Physicians should discuss CAM use and effectiveness with their patients and refer patients if appropriate.

Objective To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship—and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components.

Design A six week single blind three arm randomised controlled trial.

Setting Academic medical centre.

Participants 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale.

Interventions For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.

Main outcome measures Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life.

Results At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus “limited” versus “augmented,” respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01).Results were similar at six week follow-up.

Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.

Trial registration Clinical Trials NCT00065403.

Narcotic bowel syndrome (NBS) is a subset of opioid bowel dysfunction that is characterized by chronic or frequently recurring abdominal pain that worsens with continued or escalating dosages of narcotics. This syndrome is under recognized and may be becoming more prevalent. This may be due in the United States to increases in using narcotics for chronic non-malignant painful disorders, and the development of maladaptive therapeutic interactions around its use. NBS can occur in patients with no prior gastrointestinal disorder who receive high dosages of narcotics after surgery or acute painful problems, among patients with functional GI disorders or other chronic gastrointestinal diseases who are managed by physicians unaware of the hyperalgesic effects of chronic opioids. The evidence for the enhanced pain perception is based on: a) activation of excitatory anti-analgesic pathways within a bimodal opioid regulation system, b) descending facilitation of pain at the Rostral Ventral Medulla and pain facilitation via dynorphin and CCK activation, and c) glial cell activation that produces morphine tolerance and enhances opioid induced pain. Treatment involves early recognition of the syndrome, an effective physician patient relationship, graded withdrawal of the narcotic according to a specified withdrawal program and the institution of medications to reduce withdrawal effects.

Aims

To compare quality of life (QOL) for patients with irritable bowel syndrome (IBS) between the U.S. and Japan, it is indispensable to develop common instruments. The IBS-QOL, which is widely used in Western countries, was translated into Japanese as there has been a lack of Japanese disease-specific QOL measures for IBS.

Methods

The original 34 items of the IBS-QOL were translated from English into Japanese through two independent forward translations, resolution, back translation, and resolution of differences. Forty nine patients who had GI symptoms but did not have any organic diseases (including 30 IBS patients diagnosed by Rome II criteria) were recruited from Tohoku University Hospital in Sendai, Japan and completed a Japanese version of the IBS-QOL (IBS-QOL-J) concomitant with a Japanese version of the IBS severity index (IBSSI-J) twice within 7–14 days.

Results

The IBS-QOL-J demonstrated high internal consistency (Cronbach's alpha; 0.96) and high reproducibility (intraclass correlation coefficient; 0.92, p < 0.001). Convergent analyses confirmed that the overall score of IBS-QOL-J was significantly correlated with overall severity of IBS symptoms on the IBSSI-J (r = -0.36, p = 0.01) and with the individual items on the IBSSI-J that assess interference with life in general (r = -0.47, p = 0.001) and dissatisfaction with bowel habits (r = -0.32, p < 0.05). Eight patients who reported continuous abdominal pain in the past 6 months had significantly lower scores in the IBS-QOL-J than those who did not (53.7 +- 12.7 vs. 73.6 +- 19.5, p < 0.01). Age, sex, education or marital status did not affect scores on the measure.

Conclusion

The IBS-QOL-J is a reliable instrument to assess the disease-specific QOL for IBS. Considering cross-cultural comparison, this measure is likely to be a valuable tool to investigate the QOL in Japanese patients with IBS.

Computer-based clinical simulations for medical education exhibit wide variation in structure and format, yet few studies have examined which formats are optimal for particular educational settings. This study is a randomized comparison of the same simulated case offered in three formats: a “pedagogic” format offering explicit educational support, a “high fidelity” format attempting to model clinical reasoning in the real world, and a “problem solving” format that required students to express specific diagnostic hypotheses. Data were collected from rising third year medical students using a posttest, attitudinal questionnaire, students' writeups of the case, and log files of students' progress through the simulation. Student performance on all measures differed significantly by format. In general, students using the pedagogic format were more proficient but less efficient. They acquired more information but were able to do proportionately less with it. Students at this level had difficulty generating queries for clinical information using natural language. The results suggest that the format of computer-based simulations is important educationally; a format that works well for one learner population may not work as well for another population with different characteristics.