Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome.

BACKGROUND: End-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. METHODS: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. KEY RESULTS: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. CONCLUSIONS AND INFERENCES: An ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.

Communication breakdown between physicians and IBS sufferers: what is the conundrum and how to overcome it?

Irritable bowel syndrome is a disorder of gut-brain interaction that leads to a significant healthcare burden worldwide. A good physician-patient relationship is fundamental in managing patients who suffer from this poorly understood chronic disease. We highlight possible reasons for breakdown in communication between physicians and irritable bowel syndrome sufferers and suggest possible ways to overcome such pitfalls.

Development and validation of the Patient-Physician Relationship Scale among patients with irritable bowel syndrome.

BACKGROUND: An effective patient-physician relationship (PPR) is essential to the care of patients with irritable bowel syndrome (IBS). We sought to develop and validate an IBS-specific instrument to measure expectations of the PPR. METHODS: We conducted structured focus groups about PPRs with 12 patients with IBS. Qualitative analysis was used to generate a questionnaire (the Patient-Physician Relationship Scale [PPRS]), which was modified with input from content experts and usability testing. For validation, we administered it online to US adults with IBS. Participants also completed the Functional Bowel Disorder Severity Index, the Rome III Adult Functional gastrointestinal (GI) Disorder Criteria Questionnaire, and modified versions of the Communication Assessment Tool (CAT-15) and Patient-Doctor Relationship Questionnaire (PDRQ-9). We performed principal components factor analysis for the PPRS. KEY RESULTS: The PPRS contained 32 questions with responses on a 7-item Likert scale. Themes included interpersonal features, clinical care expectations, and aspects of communication. One thousand and fifty-four eligible individuals completed the survey (88% completion rate). Most participants were middle aged (mean 48 years, SD 16.3), white (90%), and female (86%). Factor analysis showed only one relevant factor, relating to quality of PPR. The final scale ranged from possible-96 to +96 (mean 62.0, SD 37.6). It correlated moderately with the CAT-15 (r=.40, P<.001) and PDRQ-9 (r=.30, P<.001), establishing concurrent validity. CONCLUSIONS & INFERENCES: We describe the development and validation of the first questionnaire for use in measuring patient expectations of the PPR, which can be used for future outcomes studies and training physicians.

What's new in Rome IV?

The functional gastrointestinal disorders (FGIDs) are the most common disorders seen in Gastroenterology clinical practice. The Rome process has generated consensus definitions of FGIDS, allowing to subdivide patients into diagnostic categories based on the symptom pattern. The Rome IV consensus, presented in 2016, is the most recent update of this diagnostic scheme. This article summarizes the main changes, which include the use of epidemiology-based symptom thresholds to define FGIDs, characterization of FGIDS as disorders of Gut-Brain interaction, and updates of criteria for esophageal disorders, irritable bowel syndrome and Biliary and Sphincter of Oddi disorders based on scientific and technical progress made over the last decade. The Rome IV consensus provides a standard for clinical and research approach to FGIDS for the coming years.

Centrally targeted pharmacotherapy for chronic abdominal pain.

BACKGROUND: Chronic abdominal pain in the context of the functional gastrointestinal disorders departs from a more traditional approach to treating gastrointestinal symptoms. Chronic abdominal pain involves a dysregulation of brain-gut modulation of afferent signaling, so treatments directed toward the gut are not usually sufficient to achieve a clinical response. Rather the methods of treatment depend on re-establishing central pain regulation. PURPOSE: A conceptual model of predisposing, precipitating, and perpetuating factors is used to explain how a situation of chronic pain develops and it provides the evidence for central neuron degeneration as relevant to this chain of events. The rationale for centrally targeted medications, in particular antidepressants, is discussed with regard to effects independent of their role in treating psychiatric disorders: with regard to downregulation of afferent pain signals and their potential role in neuron proliferation. Finally, guiding examples of which drug to use and treatment combinations involving multiple drugs, augmentation treatment, are outlined and some brief clinical cases of centrally targeted pharmacotherapy.

Development and pilot testing of an integrated, web-based self-management program for irritable bowel syndrome (IBS).

BACKGROUND: Although essential, many medical practices are unable to adequately support irritable bowel syndrome (IBS) patient self-management. Web-based programs can help overcome these barriers. METHODS: We developed, assessed, and refined an integrated IBS self-management program (IBS Self-care). We then conducted a 12-week pilot test to assess program utilization, evaluate its association with patients' self-efficacy and quality of life, and collect qualitative feedback to improve the program. KEY RESULTS: 40 subjects with generally mild IBS were recruited via the Internet to participate in a 12-week pilot study. Subjects found the website easy to use (93%) and personally relevant (95%), and 90% would recommend it to a friend. Self-rated IBS knowledge increased from an average of 47.1 on a 100-point VAS scale (SD 22.1) at baseline to 77.4 (SD: 12.4) at week 12 (p < 0.0001). There were no significant changes in patient self-efficacy (Patient Activation Measure) or quality of life (IBS -Quality of Life Scale). CONCLUSIONS & INFERENCES: The IBS Self-Care program was well received by users who after 12 weeks reported improved knowledge about IBS, but no significant changes in self-efficacy or quality of life. If applied to the right population, this low cost solution can overcome some of the deficiencies of medical care and empower individuals to better manage their own IBS.

Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation.

BACKGROUND: Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral µ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. PURPOSE: At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: 'A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency'. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group's discussion and consensus recommendations for patient care and research are presented in this article.

Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation.

BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) significantly decreases quality of life and the ability to perform daily living activities. AIM: To demonstrate the long-term safety, tolerability and patient outcomes of lubiprostone in patients with IBS-C. METHODS: This extension study enrolled 522 IBS-C patients who had completed one of two randomised phase 3 studies. All enrolled patients received open-label lubiprostone orally for 36-weeks (8 mcg, twice daily). The primary objective was the assessment of long-term safety and tolerability, monitored via adverse events (AEs), laboratory parameters and vital signs. Additional outcome endpoints included monthly responder rates and patient evaluations of IBS-C symptom severity and impact on quality of life. RESULTS: The evaluable safety population comprised of 520 patients; 476 of which had patient reported outcome data available. The overall safety profile of lubiprostone during this study was similar to that observed in the preceding phase 3 studies. The most common AEs were diarrhoea (11.0%), nausea (11.0%), urinary tract infection (9.0%), sinusitis (9.0%) and abdominal distention (5.8%). Diarrhoea and nausea were the most common treatment-related AEs. No serious AEs were considered treatment-related. Seventeen patients discontinued due to a treatment-related AE, of which diarrhoea and nausea accounted for six (1.2%) and three (0.6%) respectively. For responder rates and patient-evaluated parameters (n = 476), all groups experienced significant improvements from baseline, with initial improvements maintained throughout the study. CONCLUSION: In patients with irritable bowel syndrome with constipation, lubiprostone 8 mcg twice daily was found to be safe and well tolerated over 9-13 months of treatment.

Review article: the functional abdominal pain syndrome.

BACKGROUND: Functional abdominal pain syndrome (FAPS) is a debilitating disorder with constant or nearly constant abdominal pain, present for at least 6 months and loss of daily functioning. AIM: To review the epidemiology, pathophysiology and treatment of FAPS. METHODS: A literature review using the keywords: functional abdominal pain, chronic abdominal pain, irritable bowel syndrome and functional gastrointestinal disorders. RESULTS: No epidemiological studies have focused specifically on FAPS. Estimates of prevalence range from 0.5% to 1.7% and tend to show a female predominance. FAPS pathophysiology appears unique in that the pain is caused primarily by amplified central perception of normal visceral input, rather than by enhanced peripheral stimulation from abdominal viscera. The diagnosis of FAPS is symptom-based in accordance with the Rome III diagnostic criteria. These criteria are geared to identify patients with severe symptoms as they require constant or nearly constant abdominal pain with loss of daily function and are differentiated from IBS based on their non-association with changes in bowel habit, eating or other gut-related events. As cure is not feasible, the aims of treatment are reduced suffering and improved quality of life. Treatment is based on a biopsychosocial approach with a therapeutic patient-physician partnership at its base. Therapeutic options include central nonpharmacological and pharmacological modalities and peripheral modalities. These can be combined to produce an augmentation effect. CONCLUSION: Although few studies have assessed functional abdominal pain syndrome or its treatment specifically, the treatment strategies outlined in this paper appear to be effective.

The development and validation of a new coeliac disease quality of life survey (CD-QOL).

BACKGROUND: Previous studies on coeliac disease (CD)-related quality of life (QOL) have been limited by their use of a 'generic' rather than coeliac disease-specific assessment instruments. AIM: To develop and psychometrically validate a new coeliac disease-specific instrument, the CD-QOL. METHODS: Through a series of focus groups, we elicited items from patients that related to the specific nature of their disease and its impact on their basic needs. Through expert review, cognitive debriefing with patients and pilot testing, a scale was developed, refined and administered to 387 patients on a gluten-free diet from both community-based support groups and a tertiary care referral centre. Finally, a formal validation study was conducted to assess the psychometric properties of the CD-QOL. RESULTS: The final CD-QOL has 20 items across four clinically relevant subscales (Limitations, Dysphoria, Health Concerns, and Inadequate Treatment). The CD-QOL has high internal consistency, reliability, and psychometric validation indicates both convergent and discriminate validity. CONCLUSIONS: The CD-QOL is a reliable and valid measure of coeliac disease related QOL. As a new disease-specific instrument, it is likely to be a useful tool for evaluating patients with this disorder.

Constipation does not develop following elective hysterectomy: a prospective, controlled study.

Although there have been reports that women develop constipation following hysterectomy, previous studies were either retrospective or uncontrolled. The aim of this prospective, controlled study was to assess whether constipation develops after elective hysterectomy. Women undergoing elective gynaecological surgery were compared to matched non-surgery controls at enrollment and 3 and 12 months after surgery. The subset of women who underwent elective hysterectomy was the study group for the present report. Fifty-eight of the 132 elective surgery patients underwent hysterectomy and were compared to 123 controls. There was no difference between the groups at any follow-up point in functional constipation (P = 1.0), frequency of stools (P = 0.92), stool consistency (P = 0.42), straining (P = 0.43), feeling of obstruction (P = 0.6) or need to manually evacuate stool (P = 1.0). Significantly, more hysterectomy patients without baseline pain did develop abdominal pain at 3 or 12 months than non-surgery controls (16.7% vs 3.6%, P = 0.008). We conclude that there was no significant change in bowel habit or stool characteristics in women undergoing hysterectomy even though many developed abdominal pain. This prospective, controlled study challenges existing data regarding the effect of hysterectomy on constipation.

Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies.

BACKGROUND: Effective treatments for irritable bowel syndrome with constipation (IBS-C) are lacking. AIM: To assess the efficacy and safety of lubiprostone in IBS-C. METHODS: A combined analysis was performed among 1171 patients with a Rome II diagnosis of IBS-C in two phase-3 randomized trials of lubiprostone 8 mcg vs. placebo twice daily for 12 weeks. Using a balanced seven-point Likert scale ranging from significantly relieved (+3), to significantly worse (-3), patients responded on their electronic diary to the question: 'How would you rate your relief of IBS symptoms over the past week compared to how you felt before you entered the study?'. The primary efficacy endpoint was the percentage of overall responders. RESULTS: Using an intent-to-treat analysis with last observation carried forward, a significantly higher percentage of lubiprostone-treated patients were considered overall responders compared with those treated with placebo (17.9% vs. 10.1%, P=0.001). Patients treated with lubiprostone reported a similar incidence of adverse events to those treated with placebo. CONCLUSIONS: The percentage of overall responders based on patient-rated assessments of IBS-C symptoms was significantly improved in patients treated with lubiprostone 8 mcg twice daily compared to those treated with placebo. Lubiprostone was well tolerated with a favourable safety profile.

Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress.

Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS), although the issue is still under debate. The aim of this study was to determine the prevalence of SIBO in those with IBS and its association with colonic motility, bowel symptoms and psychological distress. Sucrose hydrogen and methane breath tests were performed in 158 IBS patients and 34 healthy controls (HC). Thresholds for pain and urgency were tested by barostat in the descending colon. The motility index (MI) was calculated as the average area under the curve for all phasic contractions. Questionnaires assessed psychological distress, IBS symptom severity (IBS-SS), IBS quality of life (IBS-QOL) and self-reported bowel symptoms. Fifty-two of 158 (32.9%) IBS patients had abnormal breath tests compared with six of 34 (17.9%) HC (chi(2) = 0.079). SIBO (SIBO+) and non-SIBO (SIBO-) patients did not differ in the prevalence of IBS subtypes, IBS-SS, IBS-QOL and psychological distress variables. IBS patients had a greater post-distension increase in MI than HC, but there was no difference between SIBO+ and SIBO- patients. Predominant methane producers had higher urge thresholds (28.4 vs 18.3, P < 0.05) and higher baseline MI (461 vs 301.45, P < 0.05) than SIBO- IBS patients, and they reported more 'hard or lumpy stools' when compared with predominant hydrogen producers (P < 0.05) and SIBO- IBS patients (P < 0.05). SIBO is unlikely to contribute significantly to the pathogenesis of IBS. Methane production is associated with constipation.

Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation.

BACKGROUND: Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation. AIM: To assess the efficacy and safety of three lubiprostone doses for irritable bowel syndrome with constipation. METHODS: 195 irritable bowel syndrome with constipation patients received daily doses of 16 [8 microg twice daily (b.d.)], 32 (16 microg b.d.) or 48 microg (24 microg b.d.) lubiprostone or placebo b.d. for 3 months. Gastrointestinal parameters were recorded in diaries daily by patients. RESULTS: After 1 month, lubiprostone showed significantly greater improvements in mean abdominal discomfort/pain scores vs. placebo (P = 0.023). After 2 months, all lubiprostone groups showed significantly greater improvements in mean abdominal discomfort/pain scores (P < or = 0.039). After 3 months of treatment, the improvement in each lubiprostone arm was greater than placebo, but the test for trend was no longer significant. Treatment with lubiprostone showed significantly higher rates of gastrointestinal adverse events (P = 0.020), especially diarrhoea and nausea. CONCLUSION: Lubiprostone significantly improved gastrointestinal symptoms of irritable bowel syndrome with constipation at all doses. Higher doses of lubiprostone, especially the 48 microg/day group, were associated with more gastrointestinal adverse events. From these data, the 16 microg/day dose demonstrated the optimal combination of efficacy and safety. These results warrant further study of lubiprostone for treatment of irritable bowel syndrome with constipation patients.

Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.

BACKGROUND: Studies suggest that the positive predictive value of the Rome II criteria for diagnosing irritable bowel syndrome can be enhanced by excluding red flag symptoms suggestive of organic diseases. AIM: We assessed the utility of red flags for detecting organic diseases in patients diagnosed irritable bowel syndrome by their physicians. METHODS: Systematic chart reviews were completed in 1434 patients with clinical diagnoses of irritable bowel syndrome, abdominal pain, diarrhoea or constipation, who also completed questionnaires to identify Rome II criteria for irritable bowel syndrome and red flag symptoms. RESULTS: The overall incidence of gastrointestinal cancer was 2.5% (but 1.0% in those with irritable bowel syndrome), for inflammatory bowel disease 2.0% (1.2% in irritable bowel syndrome), and for malabsorption 1.3% (0.7% in irritable bowel syndrome). Red flags were reported by 84% of the sample. The positive predictive value of individual red flags for identifying organic disease was 7-9%. Excluding any patient with a red flag improved the agreement between Rome II and clinical diagnosis by a modest 5%, but left 84% of patients who were diagnosed with irritable bowel syndrome by their physicians, without a diagnosis. CONCLUSIONS: Red flags may be useful for identifying patients who require additional diagnostic evaluation, but incorporating them into the Rome criteria would not improve sensitivity and would result in too many missed irritable bowel syndrome diagnoses.

Brain imaging and its implications for studying centrally targeted treatments in irritable bowel syndrome: a primer for gastroenterologists.

Research into brain-gut interactions, and the use of brain imaging, as potential investigative tools for functional gastrointestinal disorders, such as irritable bowel syndrome, is a promising new area. Studies are beginning to identify the structure and function of regions of the brain and their relationships to pain perception, stress, and other psychosocial variables. These imaging modalities may also have diagnostic potential, and perhaps even therapeutic applications, particularly with regard to understanding the benefit of centrally targeted modalities such as antidepressants and psychological treatments.

The usual medical care for irritable bowel syndrome.

AIMS: To determine what constitutes usual medical care for irritable bowel syndrome, which patient characteristics influence choice of treatment and how satisfied patients are with care. METHODS: Patient encounters in a health maintenance organization were prospectively monitored to identify visits coded irritable bowel syndrome, abdominal pain, constipation or diarrhoea. Within 2 weeks these patients were sent postal questionnaires (n = 1770, 59% participation) to assess patient characteristics and treatment recommendations. Responders were sent follow-up questionnaires 6 months later (77% participation) to assess adherence and satisfaction with treatment. RESULTS: Treatments employed most frequently were dietary advice, explanation, exercise advice, reassurance, advice to reduce stress and antispasmodic medications. Primary care physicians and gastroenterologists provided similar treatments. Patient confidence was higher for lifestyle advice (63-67, 100-point scale) than for medications (46-59). However, adherence was greater for medications (62-79 vs. 59-69, 100-point scale). Satisfactory relief was reported by 57%, but only 22% reported that symptom severity was reduced by half. Usual medical treatment was less effective for irritable bowel syndrome than for constipation, diarrhoea, or abdominal pain. CONCLUSIONS: Usual medical care for irritable bowel syndrome emphasizes education and lifestyle modification more than drugs; patients have a greater expectation of benefit from lifestyle modification than drugs. Overall 57% of irritable bowel syndrome patients report satisfactory relief.

Sexual and physical abuse are not associated with rectal hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND: Patients with irritable bowel syndrome (IBS) have reduced pain thresholds for rectal distension. In addition, the prevalence of sexual/physical abuse in referred IBS patients is high and is associated with greater pain reporting, poorer health status, and poorer outcome. This lead to a hypothesis that abuse history may sensitise patients to report pain at a lower threshold. AIM: To compare rectal pain thresholds in women with IBS who had a history of severe abuse to IBS women with no history of abuse. METHODS: We studied 74 IBS patients with a history of severe physical and/or sexual abuse and 85 patients with no history of abuse. Abuse history was assessed by a previously validated self-report abuse screening questionnaire. Rectal sensory thresholds were assessed using an electronic barostat and determined by the ascending method of limit (AML) and by the tracking technique. RESULTS: IBS patients with a history of severe abuse had significantly higher rectal pain thresholds, as measured by AML (F (1, 111) = 6.06; p = 0.015) and the tracking technique (F (1, 109) = 5.21; p = 0.024). Patients with a history of severe abuse also reported a significantly higher threshold for urgency to defecate (F (1, 113) = 11.23; p =.001). CONCLUSION: Severe sexual/physical abuse is associated with higher urge and pain thresholds for rectal distension in IBS patients. This suggests that the greater pain reporting and poorer health status in IBS patients with abuse history are not related to increased rectal pain sensitivity. Further studies are needed to determine the causes of these findings.