Kenneth Barshop

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

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

Duodenal rather than antral motility contractile parameters correlate with symptom severity in gastroparesis patients

Studies of symptomatic gastroparetics consistently find poor correlation with gastric emptying. We hypothesized that concomitant small bowel dysmotility may play a role in symptom causation in gastroparesis and sought to test this hypothesis by using wireless motility capsule (WMC) testing to simultaneously measure antral and duodenal area under pressure curve (AUC) in patients with delayed gastric emptying.

The investigational drug camicinal for the treatment of gastroparesis

Introduction: Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction that presents with upper gastrointestinal symptoms. Despite its growing prevalence, there remains an unmet clinical need for more efficacious prokinetic treatment options. The current market includes prokinetic agents that reduce gastroparesis symptoms. However, adverse drug effects and tachyphylaxis with repeated dosing are among the factors that limit their use. Camicinal (GSK962040) is the most advanced, small-molecule, selective motilin receptor agonist with therapeutic potential to date. Areas covered: This article reviews the literature on the limitations of current prokinetic agents used in the treatment of gastroparesis. It also summarizes the current evidence and influential clinical trial results involving the investigational drug camicinal, and shares its preliminary findings from the literature. Expert opinion: Camicinal represents a new opportunity as a treatment in a clinical area in need of new agents. There is emerging literature to support how the drug addresses both gastroparesis symptoms and dysmotility with no significant adverse effects or tachyphylaxis reported to date. Challenges remain in getting a new compound approved for gastroparesis. However, careful design of future trials will help to continue the record of success camicinal trials have had thus far.

New Pathways, New Targets: Visceral Hypersensitivity Pathogenesis in Irritable Bowel Syndrome

New Pathways, New Targets: Visceral Hypersensitivity Pathogenesis in Irritable Bowel Syndrome

Rectosigmoid Localization of Radiopaque Markers Does Not Correlate with Prolonged Balloon Expulsion in Chronic Constipation: Results from a Multicenter Cohort

OBJECTIVES:Ingestion of radiopaque markers (ROMs) is a common means of assessing colonic transit time in chronic constipation. Because anorectal manometry (ARM) testing for pelvic floor dysfunction is mostly limited to academic centers, clinicians frequently use rectosigmoid accumulation of markers as a surrogate for pelvic floor dysfunction. We sought to determine whether rectosigmoid localization of markers on a ROM study correlated with measures of pelvic floor dysfunction by ARM and balloon expulsion testing.METHODS:We assembled a multicenter, retrospective cohort of patients diagnosed with chronic constipation who underwent both transit testing by ROM transit testing and ARM with balloon expulsion testing. We compared the proportion of patients with outlet obstruction by rectoanal pressure gradient or prolonged balloon expulsion stratified by marker location.RESULTS:There were 610 patients with both ROM testing and ARM with balloon expulsion testing. The mean age was 44 years and 526 were women (86%). Eighty-one (13%) patients had markers confined to the rectosigmoid area alone and were compared with 529 patients with markers elsewhere (51%) or no retained markers (49%). Of those with markers confined to the rectosigmoid colon, 48 (59%) had a prolonged balloon expulsion compared with 276 (52%) who did not have rectosigmoid markers (P=0.28). The mean rectoanal gradient for patients with markers in the rectosigmoid colon was −29±46 mm Hg compared with −34±59 mm Hg for all others (P=0.59).CONCLUSIONS:Among patients with chronic constipation undergoing ROM transit testing, there is no association between rectosigmoid location of markers and rectoanal gradient or prolonged balloon expulsion.

Resting anal pressure, not outlet obstruction or transit, predicts healthcare utilization in chronic constipation: a retrospective cohort analysis.

Chronic constipation is common and exerts a considerable burden on health‐related quality of life and healthcare resource utilization. Anorectal manometry (ARM) and colonic transit testing have allowed classification of subtypes of constipation, raising promise of targeted treatments. There has been limited study of the correlation between physiological parameters and healthcare utilization.

Connecting the Dots Between Gastrointestinal Motility and Symptoms Using Wireless Motility Capsule Testing

The overlap of symptoms experienced by subjects with visceral hypersensitivity and those with motility disorders often confounds clinical diagnosis. The ascertainment of the physiological mechanisms responsible for GI symptoms is often challenging for clinicians and investigators alike. As a result, treatment of these disorders is largely empiric, often based on patient symptoms rather than on the underlying pathophysiology. Although slowed gastric motility is the defining feature of gastroparesis, the correlation between gastric emptying time and symptom severity is not well established [1, 2]. Such a correlation would simplify the treatment of gastroparesis since accelerating gastric motility with prokinetic agents would have a high probability of improving the cardinal symptoms of nausea, vomiting, heartburn, bloating, upper abdominal pain, and postprandial fullness. Despite no demonstrated correlation, it is evident in clinical practice that a subset of gastroparesis patients respond well to prokinetic agents, whereas others are refractory to treatment. Predicting the patient subset that is likely to respond to prokinetics would be of great clinical use, since it would reduce the number of patients unnecessarily exposed to ineffective treatments and associated adverse drug effects. If such a biomarker correlating symptom with a measurable process is to emerge, it will be essential to segregate patients with ‘‘pure’’ (homogeneous) motility disorders from those with visceral hypersensitivity. Albeit an oversimplification of a heterogeneous group, this population can be thought of as on a spectrum, with pure motility disorders on one extreme, and pure sensory disorders on the other. According to the paradigm, pure prokinetic therapy would have minimal effect on symptom alleviation in patients with pure sensory dysfunction, since their symptoms are generated by visceral neural hypersensitivity, not hypomotility. On the other extreme, patients with pure motility disorders would in theory benefit from prokinetic agents since they treat the underlying pathophysiology. In actual clinical practice, most patients have mixed etiology, which impedes successful treatment. Without a biomarker correlating gastrointestinal symptoms to motility or other measures, empiric therapies are the norm. The wireless motility capsule (WMC) is a modality used to assess multiregional gut motility in this patient population that has been increasingly used, mostly at advanced tertiary care centers. The WMC is a pill-sized device that travels throughout the gastrointestinal tract for 5 days after ingestion, continuously sampling intraluminal pH, temperature, pressure, and motility parameters. Unlike conventional antroduodenal manometry, the enhanced capabilities of the WMC support the simultaneous and convenient measurement of antroduodenal contractility and transit enabling regional or full gut assessment of motility. In this issue of Digestive Diseases and Sciences, Arora et al. [3] highlight this complexity in their article ‘‘Clinical utility of wireless motility capsule in patients with suspected multiregional gastrointestinal dysmotility.’’ They characterize their patients with suspected motility disorders using WMC testing, reporting multiregional dysmotility in nearly half of their sizable population of patients with upper and lower GI symptoms, in concordance with K. Barshop Pritzker School of Medicine, University of Chicago, Chicago, IL, USA

Depression but Not Symptom Severity is Associated With Work and School Absenteeism in Refractory Chronic Constipation

Goals: We sought to determine the patient characteristics associated with increased absenteeism and Emergency Department (ED) utilization among patients with constipation. Background: Chronic constipation is associated with significant direct and indirect economic costs. There has been limited study of the predictors of direct and indirect costs in a population with refractory constipation. Study: We conducted a cross-sectional cohort study of patients with chronic constipation who presented to a tertiary care center for anorectal manometry. We used standardized instruments to assess disease severity, quality of life, somatization, and psychiatric comorbidities. We used multivariable logistic regression to determine the predictors of work and school absenteeism as well as ED visits for constipation. Results: There were 148 consecutive patients enrolled (87% female, mean age 43) of whom 32 (21.6%) had high absenteeism and 36 (24.3%) visited the ED for constipation in the past year. Patients with high absenteeism and ED visits were more likely to be depressed (56.3% vs. 18.5%, P<0.0001 for high absenteeism; 47.2% vs. 19.6%, P<0.01 for ED visits). After multivariable adjustment and sensitivity analyses, only depression (OR, 4.41; P<0.01) was associated with increased absenteeism while there was a trend toward an association between depression and ED visits (OR, 2.57; P=0.067). Symptom severity was not associated with high absenteeism or ED utilization. Conclusions: Among patients with chronic constipation, depression is a stronger predictor of absenteeism than symptom severity. Depression may drive a portion of the indirect costs of chronic constipation.

Number of retained radiopaque markers on a colonic transit study does not correlate with symptom severity or quality of life in chronic constipation

Ingestion of radiopaque markers (ROM) is frequently used to determine colonic transit in chronic constipation. Although ≥20% of retained markers at 5 days defines slow‐transit constipation, some clinicians use the number of retained markers to determine disease severity.

Colonic motor response to wakening is blunted in slow transit constipation as detected by wireless motility capsule

Background: Chronic constipation may be categorized as normal transit (NTC), slow transit (STC), or outlet obstruction. Colonic wake response is a relative increase in colonic motility upon awakening. Colonic manometry studies have demonstrated attenuated wake response in STC. We sought to evaluate wake response among healthy (H), NTC, and STC patients using wireless motility capsule (WMC). Methods: A retrospective study of WMC data from a multicenter clinical trial and a tertiary gastroenterology clinic was performed. WMC motility parameters of contraction frequency (Ct) and area under the contraction curve (AUC) were analyzed in 20‐min windows 1‐h before and after awakening. T‐tests compared parameters between H, NTC, and STC. Linear regression analysis was performed to determine if outlet obstruction confounded data. A receiver operating characteristic curve demonstrated optimal Ct cut‐offs to define blunted wake response. Results: A total of 62 H, 53 NTC and 75 STC subjects were analyzed. At 20, 40, and 60 min after awakening, STC subjects had significantly lower mean Ct when compared to H (p < 0.001) and NTC (p < 0.01). Linear regression demonstrated that outlet obstruction was not associated with a decreased wake response (&bgr; = 3.94, (CI ‐3.12–1.00), P = 0.27). Defined at the Ct threshold of 64 at 20‐min post‐wake, blunted wake response sensitivity was 84% and specificity was 32% for chronic constipation. Conclusion: Findings of an impaired wake response in subjects with STC and not NTC adds further evidence to neuronal dysfunction as an etiology of STC, and identifies a possible temporal target for pharmacologic intervention.