Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Postprandial symptoms in patients with symptoms of gastroparesis: roles of gastric emptying and accommodation.

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, abdominal burning, and abdominal pain. There was no difference in symptoms after meal between patients with delayed (n = 66) and normal (n = 42) GE. Diabetic patients (n = 26) had greater gastric retention than idiopathic patients (n = 78), but idiopathic patients had greater postprandial nausea, stomach fullness, and abdominal pain. Water consumed during WLST averaged 421 ± 245 mL. Idiopathic patients had greater nausea scores during WLST than diabetic patients. In comparison to those with normal water consumption (≥238 mL; n = 80), patients with impaired water ingestion (<238 mL; n = 26) had increased stomach fullness, early satiety, postprandial fullness, and loss of appetite on PAGI-SYM. Patients with delayed and normal GE had similar symptom profiles during GES and WLST. Idiopathic patients had less gastric retention but more symptoms after GES meal and after WLST compared with diabetic patients. Patients with impaired water consumption during WLST had increased symptoms by PAGI-SYM. These data suggest that impaired GA, rather than GE, may be important in explaining postprandial symptoms in patients with symptoms of gastroparesis.NEW & NOTEWORTHY Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.

Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium.

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR). METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scores. RESULTS: Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P = .003), nausea (P = .003), and fullness subscales (P =.005), upper abdominal pain score (P = .04), Gastroesophageal Reflux Disease score (P = .05), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (P = .05). CONCLUSIONS: Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. NOTE: This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM.

Constipation in Patients With Symptoms of Gastroparesis: Analysis of Symptoms and Gastrointestinal Transit.

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC). METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper GI Symptoms [PAGI-SYM] and Rome III functional GI disorder questionnaire. RESULTS: Of 338 patients with symptoms of gastroparesis, 242 (71.5%) had delayed gastric emptying by scintigraphy; 298 (88.2%) also met criteria for functional dyspepsia. Severity of constipation was severe/very severe in 34% patients, moderate in 24%, and none/very mild/mild in 42%. Increasing severity of constipation was associated with increasing symptoms of gastroparesis and presence of irritable bowel syndrome (IBS). Severity of constipation was not associated with gastric retention on GES or WMC. Delayed colonic transit was present in 108 patients (32% of patients). Increasing severity of constipation was associated with increasing small bowel transit time, colonic transit time, and whole gut transit time. CONCLUSIONS: Severe/very severe constipation and delayed colon transit occurs in a third of patients with symptoms of gastroparesis. The severity of constipation is associated with severity of gastroparesis symptoms, presence of IBS, small bowel and colon transit delay, but not delay in gastric emptying. ClinicalTrials.gov Identifier: NCT01696747.

Progress in Gastroparesis - A Narrative Review of the Work of the Gastroparesis Clinical Research Consortium.

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.

Functional Dyspepsia and Gastroparesis in Tertiary Care are Interchangeable Syndromes With Common Clinical and Pathologic Features.

BACKGROUND: The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. METHODS: Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models. RESULTS: Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls. CONCLUSIONS: A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. CLINICALTRIALS. GOV IDENTIFIER: NCT00398801, NCT01696747.

Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis.

Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, "Role of Macrophages, Fibroblasts and Endothelial Cells" was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10-9; IG FDR = 6.3 × 10-12]. In DG, properdin expression correlated with GCSI bloating (r = -0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention (r = -0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis.NEW & NOTEWORTHY This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.

Functional Bowel Disorders: A Roadmap to Guide the Next Generation of Research.

In June 2016, the National Institutes of Health hosted a workshop on functional bowel disorders (FBDs), particularly irritable bowel syndrome, with the objective of elucidating gaps in current knowledge and recommending strategies to address these gaps. The workshop aimed to provide a roadmap to help strategically guide research efforts during the next decade. Attendees were a diverse group of internationally recognized leaders in basic and clinical FBD research. This document summarizes the results of their deliberations, including the following general conclusions and recommendations. First, the high prevalence, economic burden, and impact on quality of life associated with FBDs necessitate an urgent need for improved understanding of FBDs. Second, preclinical discoveries are at a point that they can be realistically translated into novel diagnostic tests and treatments. Third, FBDs are broadly accepted as bidirectional disorders of the brain-gut axis, differentially affecting individuals throughout life. Research must integrate each component of the brain-gut axis and the influence of biological sex, early-life stressors, and genetic and epigenetic factors in individual patients. Fourth, research priorities to improve diagnostic and management paradigms include enhancement of the provider-patient relationship, longitudinal studies to identify risk and protective factors of FBDs, identification of biomarkers and endophenotypes in symptom severity and treatment response, and incorporation of emerging "-omics" discoveries. These paradigms can be applied by well-trained clinicians who are familiar with multimodal treatments. Fifth, essential components of a successful program will include the generation of a large, validated, broadly accessible database that is rigorously phenotyped; a parallel, linkable biorepository; dedicated resources to support peer-reviewed, hypothesis-driven research; access to dedicated bioinformatics expertise; and oversight by funding agencies to review priorities, progress, and potential synergies with relevant stakeholders.

Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis.

BACKGROUND & AIMS: Many patients with gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship of opioid use to gastroparesis manifestations are undefined. We characterized associations of use of potent vs weaker opioids and presentations of diabetic and idiopathic gastroparesis. METHODS: We collected data on symptoms, gastric emptying, quality of life, and health care resource use from 583 patients with gastroparesis (>10% 4-h scintigraphic retention) from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Consortium, from January 2007 through November 2016. Patients completed medical questionnaires that included questions about opioid use. The opioid(s) were categorized for potency relative to oral morphine. Symptom severities were quantified by Patient Assessment of Upper Gastrointestinal Disorders Symptoms questionnaires. Subgroup analyses compared patients on potent vs weaker opioids and opioid effects in diabetic vs idiopathic etiologies. RESULTS: Forty-one percent of patients were taking opioids; 82% of these took potent agents (morphine, hydrocodone, oxycodone, methadone, hydromorphone, buprenorphine, or fentanyl). Abdominal pain was the reason for prescription for 61% of patients taking opioids. Mean scores for gastroparesis, nausea/vomiting, bloating/distention, abdominal pain, and constipation scores were higher in opioid users (P ≤ .05). Opioid use was associated with greater levels of gastric retention, worse quality of life, increased hospitalization, and increased use of antiemetic and pain modulator medications compared with nonusers (P ≤ .03). Use of potent opioids was associated with worse gastroparesis, nausea/vomiting, upper abdominal pain, and quality-of-life scores, and more hospitalizations compared with weaker opioids (tapentadol, tramadol, codeine, or propoxyphene) (P ≤ .05). Opioid use was associated with larger increases in gastric retention in patients with idiopathic vs diabetic gastroparesis (P = .008). CONCLUSIONS: Opioid use is prevalent among patients with diabetic or idiopathic gastroparesis, and is associated with worse symptoms, delays in gastric emptying, and lower quality of life, as well as greater use of resources. Potent opioids are associated with larger effects than weaker agents. These findings form a basis for studies to characterize adverse outcomes of opioid use in patients with gastroparesis and to help identify those who might benefit from interventions to prevent opioid overuse.

Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome.

BACKGROUND & AIMS: There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education. METHODS: We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion. RESULTS: A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P = .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications. CONCLUSIONS: In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.

Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis.

BACKGROUND & AIMS: Gastroparesis is a chronic disorder of the stomach characterized by nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. There is limited information on gastroparesis in minority populations. We assessed ethnic, racial, and sex variations in the etiology, symptoms, quality of life, gastric emptying, treatments, and symptom outcomes of patients with gastroparesis. METHODS: We collected information from the National Institutes of Health Gastroparesis Consortium on 718 adult patients, from September 2007 through December 2017. Patients were followed every 4 or 6 months, when data were collected on medical histories, symptoms (based on answers to the PAGI-SYM questionnaires), and quality of life (based on SF-36). Follow-up information collected at 1 year (48 week) was used in this analysis. Comparisons were made between patients of self-reported non-Hispanic white, non-Hispanic black, and Hispanic ethnicities, as well as and between male and female patients. RESULTS: Our final analysis included 552 non-Hispanic whites (77%), 83 persons of Hispanic ethnicity (12%), 62 non-Hispanic blacks (9%), 603 women (84%), and 115 men (16%). A significantly higher proportion of non-Hispanic blacks (60%) had gastroparesis of diabetic etiology than of non-Hispanic whites (28%); non-Hispanic blacks also had more severe retching (2.5 vs 1.7 score) and vomiting (2.9 vs 1.8 score) and a higher percentage were hospitalized in the past year (66% vs 38%). A significantly higher proportion of Hispanics had gastroparesis of diabetic etiology (59%) than non-Hispanic whites (28%), but Hispanics had less-severe nausea (2.7 vs 3.3 score), less early satiety (3.0 vs 3.5 score), and a lower proportion used domperidone (8% vs 21%) or had a peripherally inserted central catheter (1% vs 7%). A higher proportion of women had gastroparesis of idiopathic etiology (69%) than men (46%); women had more severe symptoms of stomach fullness (3.6 vs 3.1 score), early satiety (3.5 vs 2.9 score), postprandial fullness (3.7 vs 3.1 score), bloating (3.3 vs 2.6 score), stomach visibly larger (3.0 vs 2.1 score), and upper abdominal pain (2.9 vs 2.4 score). A lower proportion of women were hospitalized in past year (39% vs 53% of men). CONCLUSIONS: In patients with gastroparesis, etiologies, symptom severity, and treatments vary among races and ethnicities and between sexes. ClinicalTrials.gov Identifier: NCT01696747.

Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders.

BACKGROUND & AIMS: There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome. METHODS: We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis. RESULTS: Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8-1.7) (P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0-5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) (P = .04). CONCLUSIONS: In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. ClinicalTrials.gov no: NCT01149369.

Delayed Gastric Emptying Associates With Diabetic Complications in Diabetic Patients With Symptoms of Gastroparesis.

OBJECTIVES: Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE). METHODS: Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy. RESULTS: One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM (P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications. DISCUSSION: In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.

Durability and Decay of Treatment Benefit of Cognitive Behavioral Therapy for Irritable Bowel Syndrome: 12-Month Follow-Up.

BACKGROUND: There is a need for safe and effective IBS treatments that provide immediate and sustained improvement of IBS symptoms, particularly among more severe patients. The aim was to assess long-term clinical response of cognitive behavioral therapy (CBT) with reference to IBS education. METHODS: A total of 436 Rome III-diagnosed IBS patients (80% F, M age = 41 years) were randomized to: 4 session home-based CBT (minimal contact (MC-CBT)), 10 session clinic-based CBT (standard (S-CBT)), or 4 session IBS education (EDU). Follow-up occurred at 2 weeks and 3, 6, 9, and 12 months following treatment completion. Treatment response was based a priori on the Clinical Global Improvement Scale (global IBS symptom improvement) and IBS Symptom Severity Scale (IBS-SSS). RESULTS: Post-treatment CGI gains were generally maintained by MC-CBT patients at quarterly intervals through 12-month follow-up with negligible decay. For MC-CBT and S-CBT, 39 and 33% of respondents maintained treatment response at every follow-up assessment. The corresponding percent for EDU was 19%, which was significantly lower (p < 0.05) than for the CBT groups. On the IBS-SSS, therapeutic gains also showed a pattern of maintenance with trends towards increased efficacy over time in all conditions, with the mean unit reductions between baseline and follows-up being approximately -76 at immediate and approximately -94 at 12 months (-50 = clinically significant). CONCLUSIONS: For treatment-refractory IBS patients, home- and clinic-based CBT resulted in substantial and enduring relief of multiple IBS symptoms that generally extended to 12-month post treatment.

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

AIMS: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. METHODS AND RESULTS: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively. CONCLUSION: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life.

Abdominal pain can be an important symptom in some patients with gastroparesis (Gp). AIMS: (1) To describe characteristics of abdominal pain in Gp; (2) describe Gp patients reporting abdominal pain. METHODS: Patients with idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) were studied with gastric emptying scintigraphy, water load test, wireless motility capsule, and questionnaires assessing symptoms [Patient Assessment of Upper GI Symptoms (PAGI-SYM) including Gastroparesis Cardinal Symptom Index (GCSI)], quality of life (PAGI-QOL, SF-36), psychological state [Beck Depression Inventory (BDI), State-Trait Anxiety Index (STAI), PHQ-15 somatization scale]. RESULTS: In total, 346 Gp patients included 212 IG and 134 DG. Ninety percentage of Gp patients reported abdominal pain (89% DG and 91% IG). Pain was primarily in upper or central midline abdomen, described as cramping or sickening. Upper abdominal pain was severe or very severe on PAGI-SYM by 116/346 (34%) patients, more often by females than by males, but similarly in IG and DG. Increased upper abdominal pain severity was associated with increased severity of the nine GCSI symptoms, depression on BDI, anxiety on STAI, somatization on PHQ-15, the use of opiate medications, decreased SF-36 physical component, and PAGI-QOL, but not related to severity of delayed gastric emptying or water load ingestion. Using logistic regression, severe/very severe upper abdominal pain associated with increased GCSI scores, opiate medication use, and PHQ-15 somatic symptom scores. CONCLUSIONS: Abdominal pain is common in patients with Gp, both IG and DG. Severe/very severe upper abdominal pain occurred in 34% of Gp patients and associated with other Gp symptoms, somatization, and opiate medication use. ClinicalTrials.gov Identifier: NCT01696747.

Polymorphisms of 5-HTT LPR and GNß3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNß3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNß3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS: Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNß3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS: GNß3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNß3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS: GNß3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

Outcomes and Factors Associated With Reduced Symptoms in Patients With Gastroparesis.

BACKGROUND & AIMS: Gastroparesis is a chronic clinical syndrome characterized by delayed gastric emptying. However, little is known about patient outcomes or factors associated with reduction of symptoms. METHODS: We studied adult patients with gastroparesis (of diabetic or idiopathic type) enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Gastroparesis Registry, seen every 16 weeks and treated according to the standard of care with prescribed medications or other therapies at 7 tertiary care centers. Characteristics associated with reduced symptoms, based on a decrease of 1 or more in the gastroparesis cardinal symptom index (GCSI) score after 48 weeks of care, were determined from logistic regression models. Data were collected from patients for up to 4 years (median, 2.1 y). RESULTS: Of 262 patients, 28% had reductions in GCSI scores of 1 or more at 48 weeks. However, there were no significant reductions in GCSI score from weeks 48 through 192. Factors independently associated with reduced symptoms at 48 weeks included male sex, age 50 years and older, initial infectious prodrome, antidepressant use, and 4-hour gastric retention greater than 20%. Factors associated with no reduction in symptoms included overweight or obesity, a history of smoking, use of pain modulators, moderate to severe abdominal pain, a severe gastroesophageal reflex, and moderate to severe depression. CONCLUSIONS: Over a median follow-up period of 2.1 years, 28% of patients treated for gastroparesis at centers of expertise had reductions in GCSI scores of 1 or greater, regardless of diabetes. These findings indicate the chronic nature of gastroparesis. We identified factors associated with reduced symptoms that might be used to guide treatment. ClinicalTrials.gov no: NCT00398801.