Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Wireless motility capsule test in children with upper gastrointestinal symptoms.

OBJECTIVE: To compare scintigraphic gastric emptying and antroduodenal manometry (ADM) studies with the wireless motility capsule test in symptomatic pediatric patients. STUDY DESIGN: Patients aged 8-17 years with severe upper gastrointestinal symptoms (ie, nausea, vomiting, retching, abdominal pain) referred for ADM were recruited. A standardized protocol for ADM was used. On a different day, participants were given a standardized meal and then swallowed the wireless motility capsule. A wireless receiver unit worn during the study recorded transmitted data. If not performed previously, a 2-hour scintigraphic gastric emptying study was completed at the time of ADM testing. RESULTS: A total of 22 patients were recruited, of whom 21 had complete scintigraphic gastric emptying study data and 20 had complete ADM data. The wireless motility capsule test had 100% sensitivity and 50% specificity in detecting gastroparesis compared with the 2-hour scintigraphic gastric emptying study. The wireless motility capsule test detected motor abnormalities in 17 patients, compared with 10 detected by ADM. Dichotomous comparison yielded a diagnostic difference between ADM and the wireless motility capsule test (P<.01). Migrating motor complexes were recognized in all patients by both ADM and the wireless motility capsule test. The wireless motility capsule test was well tolerated in all patients, and there were no side effects. CONCLUSION: In symptomatic pediatric patients, the wireless motility capsule test is highly sensitive compared with scintigraphic gastric emptying studies in detecting gastroparesis, and seems to be more sensitive than ADM in detecting motor abnormalities.

Bear-down maneuver is a useful adjunct in the evaluation of children with chronic constipation.

BACKGROUND AND OBJECTIVES: Chronic constipation is a common problem in pediatrics and often the result of obstructed defecation. The aim of this study was to determine the use of the bear-down maneuver (BDM) in the evaluation of children with chronic constipation and to establish optimal conditions for its performance. METHODS: This retrospective study compares BDM with balloon expulsion testing (BET) during anorectal manometry in 38 children with chronic constipation. BDM was performed with 0-, 20-, 40-, and 60-mL balloon inflation. BET, performed with a 60-mL balloon, was considered normal if the balloon was expelled within 1 minute. RESULTS: Rectal pressure during BDM was 48% higher in patients able to expel the balloon during BET compared with those who could not (P < 0.05). Anal canal pressure was 46% lower in patients able to expel the balloon (P < 0.05). A rectoanal pressure differential greater than zero during BDM was 90% predictive that the subject would be able to expel the balloon. The optimal balloon inflation volume was 60 mL. CONCLUSIONS: BDM using an inflated balloon provides valuable mechanistic information in the evaluation of children with dyssynergic defecation. We found that patients often had either an insufficient rectal pressure during bear-down or an abnormally high anal canal pressure. This information may be useful in planning further treatment for these children.

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 (ß = 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.

Correction: Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease.

[This corrects the article DOI: 10.1371/journal.pone.0123861.].

Genomic and clinical effects associated with a relaxation response mind-body intervention in patients with irritable bowel syndrome and inflammatory bowel disease.

INTRODUCTION: Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. METHODS: Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. RESULTS: Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. CONCLUSIONS: In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD-and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02136745.