Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 10-20%. It affectsthe gastrointestinal tract.
This article is based on publications retrieved by a ...selective search of PubMed, with special attention to controlled trials, guidelines, and reviews.
Typical dyspeptic symptoms in functional dyspepsia include epigastric pain, sensations of pressure and fullness, nausea, and early subjective satiety. The etiology of the disorder is heterogeneous and multifactorial. Contributory causes include motility disturbances, visceral hypersensitivity, elevated mucosal permeability, and disturbances of the autonomic and enteric nervous system. There is as yet no causally directed treatment for functional dyspepsia. Its treatment should begin with intensive patient education regarding the benign nature of the disorder and with the establishment of a therapeutic pact for long-term care. Given the absence of a causally directed treatment, drugs to treat functional dyspepsia should be given for no more than 8-12 weeks. Proton-pump inhibitors, phytotherapeutic drugs, and Helicobacter pylori eradication are evidence-based interventions. For intractable cases, tricyclic antidepressants and psychotherapy are further effective treatment options.
The impaired quality of life of patients with functional dyspepsia implies the need for definitive establishment of the diagnosis, followed by symptom-oriented treatment for the duration of the symptomatic interval.
Background Remote control of capsule endoscopes might allow reliable inspection of the human stomach. Objective To assess the safety and efficacy of manipulation of a modified capsule endoscope with ...magnetic material (magnetic maneuverable capsule MMC) in the human stomach by using a handheld external magnet. Design Open clinical trial. Setting Academic hospital. Patients Ten healthy volunteers. Interventions Subjects swallowed the MMC and sherbet powder for gastric distention. An external magnetic paddle (EMP-2) was used to manipulate the MMC within the stomach. MMC responsiveness was evaluated on a screen showing the MMC film in real time. Main Outcome Measurements Safety and tolerability (questionnaire), gastric residence time of the MMC, its responsiveness to the EMP-2, area of gastric mucosa visualized. Results There were no adverse events. The MMC was always clearly attracted by the EMP-2 and responded to its movements. It remained in the stomach for 39 ± 24 minutes. In 7 subjects, both the cardia and the pylorus were inspected and 75% or more of the gastric mucosa was visualized (≥50% in all of the remaining subjects). A learning curve was clearly recognizable (identification of MMC localization, intended movements). Limitations Small amounts of fluid blocked the view of apical parts of the fundus; gastric distention was not sufficient to flatten all gastric folds. Conclusions Remote control of the MMC in the stomach of healthy volunteers using a handheld magnet is safe and feasible. Responsiveness of the MMC was excellent, and visualization of the gastric mucosa was good, although not yet complete, in the majority of subjects. The system appeared to be clinically valuable and should be developed further. (Clinical trial registration number: DE/CA05/2009031008.)
We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT(3)) antagonists in patients with nonconstipated (NC) ...or diarrhea-predominant (D)-irritable bowel syndrome (IBS).
Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT(3) antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently.
We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT(3) antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95% confidence interval CI, 1.49-1.72; I(2) = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I(2) = 22%). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95% CI, 3.28-5.60, I(2) = 65%); there was less constipation with 5-HT(3) antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95% CI, 0.41-0.99). Nine patients (0.2%) using 5-HT(3) antagonists had possible ischemic colitis versus none in control groups.
5-HT(3) antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT(3) antagonists, although the risk is lower in those with D-IBS.
IntroductionPersistent somatic symptoms (PSS) are highly prevalent in all areas of medicine; they are disabling for patients and costly for society. The subjective symptom burden often correlates ...poorly with the underlying disease severity, and patients’ needs for effective treatment are far from being met. Initial evidence indicates that, in addition to disease-specific pathophysiological processes, psychological factors such as expectations, somatosensory amplification and prior illness experiences contribute to symptom persistence in functional as well as in somatic diseases. However, prospective studies investigating the transition from acute to chronic somatic symptoms, integrating pathophysiological, psychological and social factors, are scarce. A better understanding of the multifactorial mechanisms of symptom persistence is crucial for developing targeted mechanism-based interventions for effective prevention and treatment of PSS. Thus, the overall aim of the interdisciplinary SOMACROSS research unit is to identify generic and disease-specific risk factors and aetiological mechanisms of symptom persistence across a range of diseases.Methods and analysisSeven projects will investigate risk factors and mechanisms of symptom persistence in a total of 3916 patients across 10 medical conditions. All study designs are prospective and share common assessment points, core instruments and outcome variables to allow comparison and validation of results across projects and conditions. Research will focus on the identification of generic and disease-specific mechanisms associated with unfavourable symptom course. The development of a multivariate prediction model will facilitate the understanding of the course of PSS across diseases.Ethics and disseminationAll individual SOMACROSS studies were approved by the ethics committees of the Medical Chambers Hamburg and Münster, Germany. Findings will be disseminated through peer-reviewed publications, scientific conferences and the involvement of relevant stakeholders, patients and the lay public. This interdisciplinary research unit will fundamentally contribute to earlier recognition of patients at risk, and to the development of prevention and tailored treatment concepts for PSS.
Background
Gastric emptying (GE) is delayed in a subset of patients with inflammatory bowel disease (IBD). We have shown before that altered release of gastrointestinal hormones may contribute to GE ...disturbances, but overall effects of disease activity remain unclear. Thus, we aimed to evaluate GE in patients with IBD during active disease and following therapy.
Design
A total of 20 healthy subjects (HC) and 26 patients with IBD hospitalized because of an acute episode of their disease (Crohn's disease (CD) n = 13, ulcerative colitis (UC) n = 13) underwent a standardized 13C‐octanoic acid GE breath test (baseline test). Plasma glucose, cholecystokinin (CCK), peptide YY (PYY) and glucagon‐like peptide‐1 (GLP‐1) were measured periodically throughout the test. A total of 16 patients underwent a second GE test after 3–4 months of therapy.
Results
At baseline, nine patients with IBD had pathologically delayed GE half‐time (T½ > 150 min) (P = 0·028 vs. HC). Moreover, T½ was significantly longer in the total group of patients with IBD than in HC (129 ± 12 min vs. 96 ± 7, P = 0·030). Postprandial GLP‐1 responses were elevated in IBD (P = 0·002 vs. HC) and correlated with T½ (P = 0·05). Following therapy clinical activity indices and T½ were decreased in IBD (P ≤ 0·01 vs. baseline), and T½ no longer differed from HC (P > 0·5). Moreover, GLP‐1 plasma levels decreased significantly (P = 0·031).
Conclusions
Higher disease activity in IBD is associated with prolonged GE and increased release of GLP‐1. Following effective therapy, GE is accelerated and GLP‐1 release decreases significantly. Thus, increased release of GLP‐1 from the inflamed mucosa might contribute to GE disturbances in IBD.
Background
Despite its high prevalence, opioid-induced constipation (OIC) remains under-recognised and undertreated, and its true impact on wellbeing and quality of life (QoL) may be underestimated.
...Methods
A quantitative, questionnaire-based international survey was conducted.
Results
Weak-opioid users appeared as bothered by constipation as strong-opioid users (38% vs 40%, respectively; p = 0.40), despite it causing less-severe physical symptoms and impact on QoL. Strong-opioid users meeting Rome IV OIC criteria appeared to experience greater symptomatic and biopsychosocial burden from constipation than those not satisfying these criteria. Almost one-fifth of respondents were dissatisfied with their current constipation treatment and around one-third found balancing the need for adequate pain relief with constipation side effects challenging. Consequently, more than half failed to adhere to their prescribed treatment regimens, or resorted to suboptimal strategies, e.g. 40% reduced their opioid intake, to relieve constipation. Almost 60% of healthcare professionals did not adequately counsel patients about constipation as a common side effect of opioid use.
Conclusions
Findings suggest that both weak- and strong-opioid users suffer comparable bother and decreased QoL, Rome IV criteria can identify patients with more-severe OIC, but may underdiagnose patients showing fewer symptoms, and increased education is needed to manage patients’ expectations and enable improved OIC self-management.
Background:
Two studies demonstrated the efficacy and safety of naldemedine in adult patients with chronic non-cancer pain and opioid-induced constipation (OIC). However, no studies have compared the ...efficacy of peripherally acting µ-opioid receptor antagonists in patients with adequate and inadequate responses to prior OIC therapy with laxatives. This post hoc analysis of integrated data from the two previous studies compared the efficacy of naldemedine in patients who were unsuccessfully treated with laxatives poor laxative responders (PLRs) with those who either did not receive laxatives >30 days prior to screening or those who only received rescue laxative at or after screening (non-PLRs).
Methods:
Patients with OIC were randomized to once-daily treatment with naldemedine 0.2 mg or placebo. The primary efficacy endpoint was the proportion of responders ⩾3 spontaneous bowel movements (SBMs)/week and an increase from baseline of ⩾1 SBM/week for ⩾9 weeks of the 12-week treatment period and ⩾3 weeks of the final 4 weeks of the 12-week treatment period. Additional endpoints included change in SBM frequency, change in frequency of SBMs without straining, proportion of complete SBM (CSBM) responders, change in CSBM frequency, and time to first SBM. Treatment-emergent adverse events (TEAEs) were assessed.
Results:
The analysis included 538 (317 PLRs, 221 non-PLRs) and 537 (311 PLRs, 226 non-PLRs) patients in the naldemedine and placebo arms, respectively. There were significantly more responders in the naldemedine PLR (46.4%; p < 0.0001) and non-PLR (54.3%; p = 0.0009) subgroups versus the placebo groups (30.2% and 38.9%, respectively). In both the PLR and non-PLR subgroups, naldemedine treatment was superior to placebo on all additional endpoints. Overall incidence of TEAEs in the PLR subgroups treated with naldemedine or placebo was similar.
Conclusion:
This integrated analysis further supports the efficacy and tolerability of naldemedine in the treatment of OIC and demonstrates a consistent effect in both PLR and non-PLR subgroups.
ClinicalTrials.gov identifier: NCT01965158 and NCT01993940
Objective
Many studies have been published on disorders of the gut–brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two ...regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe.
Methods
We used data collected in a population‐based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire‐4, PHQ‐4), non‐GI somatic symptoms (PHQ‐12), and access to and personal costs of doctor visits.
Results
The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 95% CI 1.08–1.20). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 1.48–1.88). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ‐4) and non‐GI somatic symptoms (PHQ‐12) had the greatest effect on the odds ratio estimates.
Conclusion
The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non‐GI somatic symptoms in Western Europe.
In this study, comparing 9487 subjects in Asia and 16,314 in Western Europe surveyed via the Internet, DGBI were more common in Western Europe. Individuals in Western Europe were more likely to have at least one (“any”) DGBI, and the same was true for DGBI by anatomical region. When adjusting for age, sex, BMI, psychological factors, non‐GI somatic symptoms, ability to visit a doctor, and personal cost of doctor visit, the difference was diminished. AOR, Adjusted OR; OR, odds ratios. *p < 0.05.
IntroductionUlcerative colitis (UC) and irritable bowel syndrome (IBS) are distressing chronic diseases associated with abdominal pain and altered bowel habits of unknown aetiology. Results from ...previous studies indicate that, across both diseases, increased levels of illness-related anxiety and dysfunctional symptom expectations contribute to symptom persistence. Thus, comparing both disorders with regard to common and disease-specific factors in the persistence and modification of gastrointestinal symptoms seems justified. Our primary hypothesis is that persistent gastrointestinal symptoms in UC and IBS can be improved by modifying dysfunctional symptom expectations and illness-related anxiety using expectation management strategies.Methods and analysisTo assess the extent to which persistent somatic symptoms are modifiable in adult patients with UC and IBS, we will conduct an observer-blinded, three-arm randomised controlled trial. A total of 117 patients with UC and 117 patients with IBS will be randomised into three groups of equal size: targeted expectation management aiming to reduce illness-related anxiety and dysfunctional symptom expectations in addition to standard care (SC, intervention 1), non-specific supportive treatment in addition to SC (intervention 2) or SC only (control). Both active intervention groups will comprise three individual online consultation sessions and a booster session after 3 months. The primary outcome is baseline to postinterventional change in gastrointestinal symptom severity.Ethics and disseminationThe study was approved by the Ethics Committee of the Hamburg Medical Association (2020-10198-BO-ff). The study will shed light onto the efficacy and mechanisms of action of a targeted expectation management intervention for persistent gastrointestinal symptoms in patients with UC and IBS. Furthermore, the detailed analysis of the complex biopsychosocial mechanisms will allow the further advancement of aetiological models and according evidence-based intervention strategies.Trial registration numberISRCTN30800023.
Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with ...racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability, but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain, and meteorism; it was also consistent across countries in Africa, Asia, and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. The seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with
treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration, and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea, racecadotril is more efficacious than placebo or
, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or
and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together, these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults.
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