Radar plots: A novel modality for displaying disparate data on the efficacy of eluxadoline for the treatment of irritable bowel syndrome with diarrhea.

BACKGROUND: Patients with irritable bowel syndrome with diarrhea (IBS-D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, is approved for the treatment of IBS-D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints. METHODS: Two double-blind, placebo-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomized patients meeting Rome III criteria for IBS-D to twice-daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1-26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency-free days, and adequate relief, and change from baseline to Week 26 in IBS-D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements. KEY RESULTS: The studies enrolled 2428 patients. Eluxadoline increased Weeks 1-26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency-free days, and adequate relief. Changes from baseline to Week 26 in IBS-D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo. CONCLUSIONS AND INFERENCES: Data presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS-D.

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.

Early response predicts a sustained response to eluxadoline in patients with irritable bowel syndrome with diarrhoea in two Phase 3 studies.

BACKGROUND: The mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, eluxadoline, is licensed in the USA for the treatment of irritable bowel syndrome with diarrhoea (IBS-D), based on the results of two large Phase 3 clinical trials. AIM: To understand the time course of treatment benefits with eluxadoline by comparing responder rates over the first month of treatment with responder rates over longer treatment intervals. METHODS: In this post hoc analysis of two Phase 3 studies, composite and adequate relief (AR) responder rates were calculated over month 1 and patients were stratified by their responder status. Cumulative counts over subsequent intervals (months 1-3, months 1-6, months 2 through 6) were tallied. RESULTS: The studies randomised 2428 patients. Over month 1, 24.6%, 22.8% and 12.5% of patients were composite responders with eluxadoline 100 mg, eluxadoline 75 mg and placebo respectively. For month 1 responders, 77.8% and 81.5% (over months 1-3) and 70.7% and 73.9% (over months 1-6) showed a continuous response with eluxadoline 100 mg and 75 mg respectively. [Correction added on 5 April 2017, after first online publication: The percentage for the responders over months 1-3 was previously wrong and has been corrected.] Of the month 1 nonresponders, <20% showed a response over months 1-3 or months 1-6. Similar results were seen for the analysis of proportions of AR responders over these time intervals. CONCLUSIONS: Over two-thirds of patients who respond over the first month retain a positive response over 6 months of treatment with eluxadoline, indicating that early clinical response to eluxadoline is associated with sustained benefits for up to 6 months in patients with IBS-D.

Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation.

BACKGROUND: Lubiprostone (8 µg b.d.) received US Food and Drug Administration (FDA) approval in 2008 for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in women aged ≥18 years. In 2012, the FDA issued new guidance for IBS-C clinical trials, recommending a composite endpoint incorporating both abdominal pain and stool frequency. AIM: In a post hoc analysis, similar criteria were applied to data from two pivotal, phase 3, double-blind, randomised trials of lubiprostone in patients with IBS-C. METHODS: Included patients had a baseline spontaneous bowel movement (SBM) frequency <3/week and abdominal pain or bloating ratings ≥1.36 on a 5-point scale [0 (absent) to 4 (very severe)]. Responders (composite endpoint) had a mean pain reduction ≥30% compared with baseline, and an increase from baseline of ≥1 SBM/week for ≥6 of the 12 treatment weeks. Lubiprostone effects on abdominal pain alone were also evaluated, as were bloating alone and in a composite endpoint with stool frequency. RESULTS: In pooled data, 325 patients received lubiprostone and 180 received placebo. Rates of response were higher with lubiprostone vs. placebo for the composite endpoint of improved pain and stool frequency (26.3% vs. 15.3%, respectively; P = 0.008) and the composite endpoint of improved bloating and stool frequency (23.8% vs. 12.6%, respectively; P = 0.012). Response rates were also higher with lubiprostone vs. placebo for abdominal pain alone (P = 0.005) and bloating alone (P = 0.012). CONCLUSION: Lubiprostone was significantly more effective than placebo in improving abdominal pain or bloating, and also in composite endpoints that included stool frequency.

Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation.

BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. AIM: To evaluate the long-term safety and tolerability of naloxegol, an oral, peripherally acting µ-opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC. METHODS: A 52-week, multicenter, open-label, randomised, parallel-group phase 3 study was conducted in out-patients taking 30-1000 morphine-equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator-chosen laxative regimen) treatment for OIC. RESULTS: The safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations. CONCLUSION: In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated.

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials.

BACKGROUND: The efficacy of rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non-constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking. AIM: To assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials. METHODS: A post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively. RESULTS: Patients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths. CONCLUSIONS: The safety and tolerability profile of rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non-constipation-predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).

A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads.

BACKGROUNDS: The development of a reliable biomarker for irritable bowel syndrome (IBS) remains one of the major aims of research in functional gastrointestinal disorders (FGIDs) and is complicated by the absence of a perfect reference standard. Previous efforts based on genetic and immune markers have showed promise, but have not been robust. AIM: To evaluate an extensive panel of gene expression and serology markers combined with psychological measures in differentiating IBS from health and between subtypes of IBS. METHODS: Of subjects eligible for analysis (N = 244), 168 met criteria for IBS (60 IBS-C, 57 IBS-D and 51 mixed), while 76 were free of any FGID. A total of 34 markers were selected based on pathways implicated in pathophysiology of IBS or whole human genome screening. Psychological measures were recorded that covered anxiety, depression and somatisation. Models differentiating disease and health were based on unconditional logistic regression and performance assessed through area under the receiver-operator characteristic curve (AUC), sensitivity and specificity. RESULTS: The performance of a combination of 34 markers was good in differentiating IBS from health (AUC = 0.81) and was improved considerably with the addition of four psychological markers (combined AUC = 0.93). Of the 34 markers considered, discrimination was derived largely from a small subset. Good discrimination was also obtained between IBS subtypes with the best being observed for IBS-C vs. IBS-D (AUC = 0.92); however, psychological variables provided almost no incremental discrimination subtypes over biological markers (combined AUC = 0.94). CONCLUSIONS: A combination of gene expression and serological markers in combination with psychological measures shows exciting progress towards a diagnostic test for IBS compared with healthy subjects, and to discriminate IBS-C from IBS-D.

Factors associated with quality of life among women with fecal incontinence.

INTRODUCTION AND HYPOTHESIS: Fecal incontinence (FI) is a distressing, highly prevalent condition affecting quality of life (QOL). The aim of our study was to identify predictors of moderate/severe health-related QOL among women with FI. METHODS: Data were collected from women presenting to a multispecialty clinic from January 2005 to July 2009 with FI. All completed questionnaires on demographics and validated instruments including the Fecal Incontinence Quality of Life Instrument (FIQL), Patient Health Questionnaire (PHQ) for depression, and Fecal Incontinence Severity Index (FISI). Logistic regression was used to identify factors associated with moderate/severe FI. RESULTS: The study included 226 women with an average age of 59.2 years (SD = 14.1); 92 % were Caucasian, 67 % were married, and the average body mass index was 30.0 (SD = 8.6). Their QOL was moderately/severely affected by FI in 35.6 %. Mean overall FIQL score was 2.5 (SD = 0.8). Median QOL subscale measures were: lifestyle = 2.7 (SD = 1.0), coping = 2.09 (SD = 0.9), depression = 2.8 (SD = 1.0), and embarrassment = 2.2 (SD = 0.9). Average FISI score was 31.6 (SD = 15.7) and average depression score on the PHQ was 8.93 (SD = 8.1). In univariate analyses, diabetes, irritable bowel symptoms, prior hysterectomy, history of previous medical care for FI, higher FISI and PHQ scores were associated with moderate/severe FIQL scores (p < 0.05). Higher PHQ scores and prior hysterectomy significantly predicted moderate/severe QOL in logistic regression analysis (p < 0.05). CONCLUSIONS: We confirm that women with higher depression scores and prior hysterectomy have moderate/severe QOL impairment. When evaluating FI, screening for depression should be undertaken.

Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints.

BACKGROUND: Treatment options that improve overall symptoms of irritable bowel syndrome with constipation (IBS-C) are lacking. AIM: A prespecified further analysis to evaluate the efficacy and safety of linaclotide, a guanylate cyclase C agonist, in patients with IBS-C, based on efficacy parameters prespecified for European Medicines Agency (EMA) submission. METHODS: Two randomised, double-blind, multicentre Phase 3 trials investigated once-daily linaclotide (290 µg) for 12 weeks (Trial 31) or 26 weeks (Trial 302) in patients with IBS-C. Prespecified primary endpoints were the EMA-recommended co-primary endpoints: (i) 12-week abdominal pain/discomfort responders [≥30% reduction in mean abdominal pain and/or discomfort score (11-point scales), with neither worsening from baseline, for ≥6 weeks] and (ii) 12-week IBS degree-of-relief responders (symptoms 'considerably' or 'completely' relieved for ≥6 weeks). RESULTS: Overall, 803 (Trial 31) and 805 patients (Trial 302) were randomised. A significantly greater proportion of linaclotide-treated vs. placebo-treated patients were 12-week abdominal pain/discomfort responders (Trial 31: 54.8% vs. 41.8%; Trial 302: 54.1% vs. 38.5%; P < 0.001) and IBS degree-of-relief responders (Trial 31: 37.0% vs. 18.5%; Trial 302: 39.4% vs. 16.6%; P < 0.0001). Similarly, significantly more linaclotide- vs. placebo-treated patients were responders for ≥13 weeks in Trial 302 (abdominal pain/discomfort: 53.6% vs. 36.0%; IBS degree-of-relief: 37.2% vs. 16.9%; P < 0.0001). The proportion of sustained responders (co-primary endpoint responders plus responders for ≥2 of the last 4 weeks of treatment) was also significantly greater with linaclotide vs. placebo in both trials (P < 0.001). CONCLUSION: Linaclotide treatment significantly improved abdominal pain/discomfort and degree-of-relief of IBS-C symptoms compared with placebo over 12 and 26 weeks. TRIAL REGISTRATION: ClinicalTrials.gov (identifiers: NCT00948818 and NCT00938717).

Factors associated with symptom severity in women presenting with fecal incontinence.

BACKGROUND: Fecal incontinence (FI) affects 2-12% of the US population. Identification of factors associated with worsening symptoms has important implications for prevention and treatment. OBJECTIVE: The aim of our study is to assess factors associated with symptom severity in women presenting with FI. DATA SOURCES: This was a prospective survey study. STUDY SELECTION: Patients presenting to the Michigan Bowel Control Program Clinic for FI were prospectively enrolled between May 2005 and May 2009. MAIN OUTCOME MEASURES: Factors associated with fecal incontinence severity. RESULTS: Data on 231 women was analyzed with a mean age of 59.2 years (SD = 14.2) and mean BMI of 30.0 (SD = 8.6); 92% were white. Mean FISI score was 32.4 (SD = 15.3). Two-thirds of patients had a type 1-4 stool on the Bristol stool scale. Forty-one percent of subjects complained of urinary incontinence, 56.2% had an episiotomy, 29% had an operative delivery, and 15.1% reported a severe laceration with childbirth. The majority of patients (86.1%) reported FI for greater than 1 year, and 65.4% had previously sought care for FI. Bivariate analysis revealed that diabetes, IBS, urinary incontinence, history of operative delivery or severe laceration, fecal urgency, longer history of symptoms, previous health care for FI, and belief in treatment were positively associated with worse FISI score. In multiple linear regression analysis, increased FI symptom severity was shown to be associated with fecal urgency (0.0004), history of episiotomy (0.04), urinary incontinence (0.02), and diabetes mellitus (0.004). LIMITATIONS: This was a cross-sectional survey study performed at a Tertiary care center. CONCLUSION: Patients with a history of episiotomy, diabetes, urinary incontinence, and fecal urgency have increased FI symptom severity. Proactive screening of patients with these medical histories is needed.

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

BACKGROUND: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). AIM: To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. METHODS: Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. RESULTS: Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). CONCLUSIONS: 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility.

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.

Measuring symptoms in the irritable bowel syndrome: development of a framework for clinical trials.

BACKGROUND: There is uncertainty about how to measure patient-reported outcomes (PROs) in IBS. The Food and Drug Administration (FDA) emphasizes that PROs must be couched in a conceptual framework, yet existing IBS PROs were not based on such a framework. AIM: To perform qualitative analyses to inform a new conceptual framework for IBS symptoms. METHODS: Following FDA guidance, we searched the literature for extant IBS questionnaires. We then performed interviews in IBS patients to learn about the illness experience in their own words. We cultivated vocabulary to inform a conceptual framework depicted with domains, sub-domains, and item categories, per FDA guidance. RESULTS: We identified 13 questionnaires with items encompassing 18 symptoms. We recruited 123 IBS patients for cognitive interviews. Major themes included: pain and discomfort are different - asking about discomfort is nonspecific and should be avoided in future PROs; bowel urgency is multifaceted - PROs should measure bowel immediacy, controllability, and predictability; and PROs should divide bloating into how it feels vs. how it looks. Symptom experience may be determined by 35-item categories within five domains: (i) pain; (ii) gas/bloat; (iii) diarrhoea; (iv) constipation; and (v) extraintestinal symptoms. CONCLUSIONS: We applied FDA guidance to develop a framework that can serve as the foundation for developing a PRO for IBS clinical trials.

Characterizing abdominal pain in IBS: guidance for study inclusion criteria, outcome measurement and clinical practice.

BACKGROUND: Although irritable bowel syndrome (IBS) is a multisymptom disorder, abdominal pain drives illness severity more than other symptoms. Despite consensus that IBS trials should measure pain to define study entry and determine efficacy, the optimal method of measuring pain remains uncertain. AIM: To determine whether combining information from multiple pain dimensions may capture the IBS illness experience more effectively than the approach of measuring 'pain predominance' or pain intensity alone. METHODS: Irritable bowel syndrome patients rated dimensions of pain, including intensity, frequency, constancy, predominance, predictability, duration, speed of onset and relationship to bowel movements. We evaluated the impact of each dimension on illness severity using multivariable regression techniques. RESULTS: Among the pain dimensions, intensity, frequency, constancy and predictability were strongly and independently associated with illness severity; the other dimensions had weaker associations. The clinical definition of 'pain predominance', in which patients define pain as their most bothersome symptom, was insufficient to categorize patients by illness severity. CONCLUSIONS: Irritable bowel disease pain is multifaceted; some pain dimensions drive illness more than others. IBS trials should measure various pain dimensions, including intensity, constancy, frequency and predictability; this may improve upon the customary use of measuring pain as a unidimensional symptom in IBS.

Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule.

BACKGROUND: The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. METHODS: Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI = Ln (Ct *sum amplitudes +1)) were analyzed for 60 min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. KEY RESULTS: Significant differences were observed between healthy and gastroparetic subjects for Ct and MI (P < 0.05). Median values of the motility parameters in gastric window were Ct = 72, MI = 11.83 for healthy and Ct = 47, MI = 11.12 for gastroparetics. In the small bowel, median values were Ct = 144.5, MI = 12.78 for healthy and Ct = 93, MI = 12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. CONCLUSIONS & INFERENCES: The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles.

The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology.

BACKGROUND: Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times. AIMS: To analyse data from a multi-centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP). METHODS: A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule. RESULTS: Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT (P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (P = 0.0054). CONCLUSIONS: In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation.

Measuring irritable bowel syndrome patient-reported outcomes with an abdominal pain numeric rating scale.

BACKGROUND: Controversy exists on how to measure patient-reported outcomes in irritable bowel syndrome (IBS) clinical trials effectively. Pain numeric rating scales (NRS) are widely used in the non-IBS pain literature. The Food and Drug Administration has proposed using the NRS in IBS. AIM: To test the psychometrics of an abdominal pain NRS in IBS. Methods We analysed data from a longitudinal cohort of Rome III IBS subjects. At entry, subjects completed a 10-point NRS, bowel symptoms, IBS severity measurements (IBS-SSS, FBDSI), health-related quality of life indices (IBS-QOL, EQ5D), and the Worker Productivity Activity Index (WPAI). We repeated assessments at 3 months along with a response scale to calculate the minimal clinically important difference. RESULTS: There were 277 subjects (82% women; age = 42 +/- 15) at baseline and 90 at 3 months. The NRS correlated cross-sectionally with IBS-SSS (r = 0.60; P < 0.0011), FBDSI (r = 0.49; P < 0.0001), IBS-QOL (r = 0.43; P < 0.0001), EQ5D (r = 0.48; P < 0.0001), presenteeism (r = 0.39; P < 0.0001), absenteeism (r = 0.17; P = 0.04) and distension (r = 0.46; P < 0.0001), but not stool frequency or form. The minimal clinically important difference was 2.2 points, correlating with a 29.5% reduction over time. CONCLUSIONS: An abdominal pain NRS exhibits excellent validity and can be readily interpreted with a minimal clinically important difference in patients with IBS. These data support the use of the NRS in IBS clinical trials.

Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease.

BACKGROUND: The proportion of patients who respond to proton pump inhibitor (PPI) therapy is about 20% lower in those with non-erosive reflux disease (NERD) than in those with erosive oesophagitis. AIM: To assess efficacy and safety of dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD patients. METHODS: In this 4-week, double-blind, placebo-controlled study, 947 NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once daily (QD). The percentages of 24-h heartburn-free days (primary) and nights without heartburn (secondary) were assessed from patients' daily diaries. Investigators also assessed symptoms. Patients completed validated quality of life and symptom severity questionnaires. RESULTS: Dexlansoprazole MR provided significantly greater median percentages of 24-h heartburn-free days (54.9% and 50.0% for the 30- and 60-mg doses vs. 17.5% for placebo, P < 0.00001) and nights without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo). Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in patients receiving dexlansoprazole MR were consistent with clinical efficacy endpoints. Percentages of patients experiencing treatment-emergent adverse events were similar among groups. CONCLUSIONS: Dexlansoprazole MR 30 and 60 mg were superior to placebo in providing 24-h heartburn-free days and nights in NERD patients. Treatment was well tolerated.