Citations

AbstractBackground and AimsUp to 50% of patients with Parkinson disease have constipation (PD‐C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD‐C is unknown. We aimed to compare anorectal function of patients with PD‐C versus idiopathic chronic constipation (CC).MethodsAnorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high‐resolution anorectal manometry (HR‐ARM) in patients with PD‐C and control patients with CC, matched for age and sex.ResultsWe identified 97 patients with PD‐C and 173 control patients. Eighty‐six patients with PD‐C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD‐C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET.In the multivariate model comparing CC and PD‐C (AUROC = 0.76), PD‐C was associated with a lower anal squeeze increment (odds ratio [OR] for PD‐C, 0.93 [95% CI, 0.91–0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03–1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66–0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08–1.26]).ConclusionsCompared with CC, PD‐C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

AbstractBackgroundHow variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut‐ brain interaction is unclear.AimsTo assess the prevalence of pharmacogenomics‐predicted drug‐gene interactions and symptom outcomes for patients with disorders of gut‐brain interaction.MethodsPatients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing. The change in symptoms from baseline to 6 months was compared for patients with variations in CYP2D6 and CYP2C19, which metabolize neuromodulators, and SLC6A4, which encodes the sodium‐ dependent serotonin transporter.ResultsAt baseline, 79 of 94 participants (84%) had at least one predicted major drug‐ gene interaction, and all 94 (100%) had at least one predicted moderate interaction. For the 44 participants who completed a survey of their symptoms at 6 months, the mean (SD) irritable bowel syndrome‐symptom severity score decreased from 284 (71) at baseline to 231 (95) at 6 months (p < 0.001). Among patients taking selective serotonin reuptake inhibitors, the decrease in symptom severity (p = 0.03) and pain (p = 0.002) scores from baseline to 6 months was greater for patients with a homozygous SLC6A4 long/long genotype (n = 30) (ie, increased serotonin transporter activity) than for patients with homozygous short/short or heterozygous long/short genotypes (n = 64). Symptom outcomes were not affected by CYP2D6 or CYP2C19 variations.ConclusionsThe homozygous SLC6A4 long/long genotype confers better symptom resolution for patients with disorders of gut‐brain interaction who take selective serotonin reuptake inhibitors than do the homozygous short/short or heterozygous long/short genotypes.

AbstractBackgroundDiarrhea and rectal urgency are risk factors for fecal incontinence (FI). The effectiveness of bowel modifiers for improving FI is unclear.MethodsIn this double‐blind, parallel‐group, randomized trial, women with urge FI were randomly assigned in a 1:1 ratio to a combination of oral clonidine (0.1 mg twice daily) with colesevelam (1875 mg twice daily) or two inert tablets for 4 weeks. The primary outcome was a ≥50% decrease in number of weekly FI episodes.Key ResultsFifty‐six participants were randomly assigned to clonidine–colesevelam (n = 24) or placebo (n = 32); 51 (91%) completed 4 weeks of treatment. At baseline, participants had a mean (SD) of 7.5 (8.2) FI episodes weekly. The primary outcome was met for 13 of 24 participants (54%) treated with clonidine–colesevelam versus 17 of 32 (53%) treated with placebo (p = 0.85). The Bristol stool form score decreased significantly, reflecting more formed stools with clonidine–colesevelam treatment (mean [SD], 4.5 [1.5] to 3.2 [1.5]; p = 0.02) but not with placebo (4.2 [1.9] to 4.1 [1.9]; p = 0.47). The proportion of FI episodes for semiformed stools decreased significantly from a mean (SD) of 76% (8%) to 61% (10%) in the clonidine–colesevelam group (p = 0.007) but not the placebo group (61% [8%] to 67% [8%]; p = 0.76). However, these treatment effects did not differ significantly between groups. Overall, clonidine–colesevelam was well tolerated.Conclusions and InferencesCompared with placebo, clonidine–colesevelam did not significantly improve FI despite being associated with more formed stools and fewer FI episodes for semiformed stools.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

AbstractBackground and objectivesChronic constipation (CC) may be caused by defecatory disorders (DDs) and associated with reduced rectal sensation. Among patients with type 1 diabetes (T1D) and CC (T1DCC patients), the prevalence of DDs and reduced rectal sensation is unknown. We sought to compare complications of T1D, anorectal dysfunction, and CC symptoms, among T1DCC patients with versus without a DD.MethodsAnorectal pressures at rest and during squeeze and evacuation, as well as rectal sensation and rectal balloon expulsion time (BET) were measured with high‐resolution anorectal manometry in 114 consecutive T1DCC patients.ResultsThirty‐seven patients (32%) had prolonged BET, suggestive of a DD. Complications of T1D included peripheral neuropathy (n = 67, 59%), retinopathy (n = 42, 37%), and nephropathy (n = 26, 23%). Among these complications, only retinopathy was associated with, that is, more prevalent in patients with normal (45%) than prolonged BET (19%). Compared with patients with normal BET, patients with prolonged BET had a lower rectal pressure (mean [SD], 32 [23] mm Hg vs. 23 [19] mm Hg,p = 0.03), greater anal pressure (91 [23] mm Hg vs. 68 [36] mm Hg,p < 0.001), and lower rectoanal gradient (−67 [30] mm Hg vs. −36 [32] mm Hg,p < 0.0001) during evacuation. Anal resting pressure and anal squeeze increment were below normal in 14 (13%) and 32 (29%) of patients and one or more rectal sensory thresholds were above normal in 34 (30%) patients; these abnormalities affected similar proportions in the normal and prolonged BET cohorts.ConclusionsAmong T1DCC patients, 37 (32%) had prolonged BET, which was associated with anorectal pressures indicative of a DD but was not associated with reduced rectal sensation, suggesting that DDs are more likely explained by abdomino‐anal dyscoordination than visceral disturbance.