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Alimentary Pharmacology & Therapeutics Jan 2021Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.
AIM
To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS
We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS
We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS
TCAs, histamine- receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
Topics: Adult; Dyspepsia; Histamine H2 Antagonists; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Proton Pump Inhibitors
PubMed: 32936964
DOI: 10.1111/apt.16072 -
Nutrients Jan 2020Probiotic is little known for its benefits on upper gastrointestinal health. The objective of this systematic review was to examine the efficacy of probiotics in...
Probiotic is little known for its benefits on upper gastrointestinal health. The objective of this systematic review was to examine the efficacy of probiotics in alleviating the frequency and severity of symptoms in gastroesophageal reflux disease (GERD) in the general adult population. The PubMed and Web of Science databases were searched for prospective studies on GERD, heartburn, regurgitation, and dyspepsia, without any limitation on sample size. The Jadad scale was used to evaluate the quality of randomized controlled trials. In total, 13 prospective studies that were published in 12 articles were included in the analysis and scored per the Jadad scale as high- (five studies), medium- (two), and low- (six) quality. One article reported on two probiotic groups; thus, 14 comparisons were included in the selected studies, of which 11 (79%) reported positive benefits of probiotics on symptoms of GERD. Five out of 11 positive outcomes (45%) noted benefits on reflux symptoms: three noted reduced regurgitation; improvements in reflux or heartburn were seen in one study; five (45%) saw improvements in dyspepsia symptoms; and nine (81%) saw improvements in other upper gastrointestinal symptoms, such as nausea (three studies), abdominal pain (five), and gas-related symptoms (four), such as belching, gurgling, and burping. In conclusion, probiotic use can be beneficial for GERD symptoms, such as regurgitation and heartburn. However, proper placebo-controlled, randomized, and double-blinded clinical trials with a sufficient number of participants are warranted to confirm its efficacy in alleviating these symptoms. Further, interventions with longer durations and an intermediate analysis of endpoints should be considered to determine the proper therapeutic window.
Topics: Gastroesophageal Reflux; Humans; Probiotics
PubMed: 31906573
DOI: 10.3390/nu12010132 -
Journal of Gastroenterology and... Sep 2022Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and... (Review)
Review
BACKGROUND AND AIM
Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and disorders of gut-brain interaction are common in this cohort and multifactorial in origin. The primary aim of this review is to arm the gastroenterologist with a clinically useful understanding of HSD/hEDS, by exploring the association of gastrointestinal disorders with HSD/hEDS, highlighting current pathophysiological understanding and providing a pragmatic approach to managing these patients.
METHODS
Literature relevant to the gastrointestinal system and hypermobile Ehlers-Danlos syndrome was systematically searched, critically appraised, and summarized.
RESULTS
Diagnosis is based upon clinical criteria and a genetic basis is yet to be defined. The prevalence of many gut symptoms, including abdominal pain (69% vs 27%, P < 0.0001), postprandial fullness (34% vs 16%, P = 0.01), constipation (73% vs 16%, P < 0.001), and diarrhea (47% vs 9%, P < 0.001) are significantly higher in HSD/hEDS compared with non-HSD/hEDS individuals. Disorders of gut-brain interaction are also common, particularly functional dyspepsia. The pathophysiology of gut symptoms is poorly understood but may involve effects of connective tissue laxity and its functional consequences, and the influence of autonomic dysfunction, medication and comorbid mental health disorders. Awareness is the key to early diagnosis. Management is limited in evidence-base but ideally should include an integrated multidisciplinary approach.
CONCLUSIONS
HSD/hEDS is a multisystemic disorder in which gastrointestinal symptoms, particularly related to disorders of gut-brain interaction are common. Deficiencies in knowledge regarding the pathophysiological processes limit evidence-based interventions and remain important areas for future research.
Topics: Ehlers-Danlos Syndrome; Gastroenterologists; Gastrointestinal Diseases; Humans; Joint Instability
PubMed: 35750466
DOI: 10.1111/jgh.15927 -
Contemporary Clinical Trials... Aug 2022Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral... (Review)
Review
The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators: A systematic review and network meta-analysis.
AIM
Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D. We evaluated the efficacy and safety of oral semaglutide compared to that of subcutaneous semaglutide, placebo, and other GLP-1 RAs in the treatment of T2D.
METHODS
Randomised controlled trials of subcutaneous and oral semaglutide for glycaemic control in adults with T2D were selected from the Cochrane Central Register of Controlled Trials and PubMed. Mean differences (MDs) and risk ratios with 95% confidence intervals (CIs) were used to synthesise the results, and oral and subcutaneous semaglutide formulations were indirectly compared using mixed treatment comparisons.
RESULTS
Twelve studies were included in this review (6840 participants). Oral semaglutide (14.0 mg) significantly reduced HbA1c (MD, -1.30% [95%CI: -1.44, -1.16], P < 0.05) and body weight (MD, -3.17 kg [95%CI: -3.89, -2.45], P < 0.05) compared to placebo (MD, HbA1c: -0.32% [95%CI: -0.49, -0.15], P < 0.05; MD body weight: -2.56 kg [95%CI: -3.41, -1.71], P < 0.05), liraglutide (1.2 mg), exenatide ER (2.0 mg), and dulaglutide (1.5 mg). Oral semaglutide was slightly less effective than subcutaneous semaglutide in reducing HbA1c levels (MD: -0.26% [95%CI: -0.44, -0.07], P < 0.05) and body weight (MD: -1.08 kg [95%CI: -2.04, -0.12], P < 0.05). Oral semaglutide increased the incidence of adverse events (nausea, diarrhoea, dyspepsia, and vomiting) compared to placebo, liraglutide (1.2 mg), exenatide (ER, 2.0 mg), and dulaglutide 1.5 mg but not compared to subcutaneous semaglutide.
CONCLUSION
Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and another GLP-1 RA in reducing HbA1c and body weight. It was superior to subcutaneous semaglutide and inferior to other GLP-1 RA comparators and placebo in terms of the incidence of adverse events. Thus, oral semaglutide provides a convenient administration route for patients who prefer oral treatments over injectable therapies.
PubMed: 35812819
DOI: 10.1016/j.conctc.2022.100944 -
Nutrients Jun 2023Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has... (Review)
Review
Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focuses on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the gluten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and functional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and single-arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, and GFD have no place in daily clinical practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may experience some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data suggest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.
Topics: Humans; Child; Adolescent; Irritable Bowel Syndrome; Gastrointestinal Diseases; Abdominal Pain; Diet, Gluten-Free; Constipation; Fermentation; Diet, Carbohydrate-Restricted; Monosaccharides
PubMed: 37375612
DOI: 10.3390/nu15122708 -
Gut Jan 2022Functional dyspepsia (FD) is a chronic disorder that is difficult to treat. may contribute to its pathophysiology. A Cochrane review from 2006 suggested that...
OBJECTIVE
Functional dyspepsia (FD) is a chronic disorder that is difficult to treat. may contribute to its pathophysiology. A Cochrane review from 2006 suggested that eradication therapy was beneficial, but there have been numerous randomised controlled trials (RCTs) published since. We evaluated impact of eradication therapy on both cure and improvement of FD, as well as whether any benefit was likely to arise from eradication of .
DESIGN
We searched the medical literature through October 2021 to identify RCTs examining efficacy of eradication therapy in -positive adults with FD. The control arm received antisecretory therapy or prokinetics, with or without placebo antibiotics, or placebo alone. Follow-up was for ≥3 months. We pooled dichotomous data to obtain a relative risk (RR) of symptoms not being cured or symptoms not improving with a 95% CI. We estimated the number needed to treat (NNT).
RESULTS
Twenty-nine RCTs recruited 6781 . -positive patients with FD. Eradication therapy was superior to control for symptom cure (RR of symptoms not being cured=0.91; 95% CI 0.88 to 0.94, NNT=14; 95% CI 11 to 21) and improvement (RR of symptoms not improving=0.84; 95% CI 0.78 to 0.91, NNT=9; 95% CI 7 to 17). There was no significant correlation between eradication rate and RR of FD improving or being cured (Pearson correlation coefficient=-0.23, p=0.907), but the effect was larger in patients with successful eradication of than with unsuccessful eradication (RR=0.65; 95% CI 0.52 to 0.82, NNT=4.5, 95% CI 3 to 9). Adverse events (RR=2.19; 95% 1.10 to 4.37) and adverse events leading to withdrawal (RR=2.60; 95% CI 1.47 to 4.58) were more common with eradication therapy.
CONCLUSION
There is high quality evidence to suggest that eradication therapy leads to both cure and improvement in FD symptoms, although the benefit is modest.
PubMed: 35022266
DOI: 10.1136/gutjnl-2021-326583 -
The Cochrane Database of Systematic... Feb 2023Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been hypothesised that the use of micro-organisms, such as probiotics and synbiotics (a mixture of probiotics and prebiotics), might change the composition of bacterial colonies in the bowel and reduce inflammation, as well as promote normal gut physiology and reduce functional symptoms.
OBJECTIVES
To assess the efficacy and safety of probiotics in the treatment of functional abdominal pain disorders in children.
SEARCH METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and two clinical trials registers from inception to October 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compare probiotic preparations (including synbiotics) to placebo, no treatment or any other interventional preparation in patients aged between 4 and 18 years of age with a diagnosis of functional abdominal pain disorder according to the Rome II, Rome III or Rome IV criteria.
DATA COLLECTION AND ANALYSIS
The primary outcomes were treatment success as defined by the primary studies, complete resolution of pain, improvement in the severity of pain and improvement in the frequency of pain. Secondary outcomes included serious adverse events, withdrawal due to adverse events, adverse events, school performance or change in school performance or attendance, social and psychological functioning or change in social and psychological functioning, and quality of life or change in quality life measured using any validated scoring tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI.
MAIN RESULTS
We included 18 RCTs assessing the effectiveness of probiotics and synbiotics in reducing the severity and frequency of pain, involving a total of 1309 patients. Probiotics may achieve more treatment success when compared with placebo at the end of the treatment, with 50% success in the probiotic group versus 33% success in the placebo group (RR 1.57, 95% CI 1.05 to 2.36; 554 participants; 6 studies; I = 70%; low-certainty evidence). It is not clear whether probiotics are more effective than placebo for complete resolution of pain, with 42% success in the probiotic group versus 27% success in the placebo group (RR 1.55, 95% CI 0.94 to 2.56; 460 participants; 6 studies; I = 70%; very low-certainty evidence). We judged the evidence to be of very low certainty due to high inconsistency and risk of bias. We were unable to draw meaningful conclusions from our meta-analyses of the pain severity and pain frequency outcomes due to very high unexplained heterogeneity leading to very low-certainty evidence. None of the included studies reported serious adverse events. Meta-analysis showed no difference in withdrawals due to adverse events between probiotics (1/275) and placebo (1/269) (RR 1.00, 95% CI 0.07 to 15.12). The results were identical for the total patients with any reported adverse event outcome. However, these results are of very low certainty due to imprecision from the very low numbers of events and risk of bias. Synbiotics may result in more treatment success at study end when compared with placebo, with 47% success in the probiotic group versus 35% success in the placebo group (RR 1.34, 95% CI 1.03 to 1.74; 310 participants; 4 studies; I = 0%; low certainty). One study used Bifidobacterium coagulans/fructo-oligosaccharide, one used Bifidobacterium lactis/inulin, one used Lactobacillus rhamnosus GG/inulin and in one study this was not stated). Synbiotics may result in little difference in complete resolution of pain at study end when compared with placebo, with 52% success in the probiotic group versus 32% success in the placebo group (RR 1.65, 95% CI 0.97 to 2.81; 131 participants; 2 studies; I = 18%; low-certainty evidence). We were unable to draw meaningful conclusions from our meta-analyses of pain severity or frequency of pain due to very high unexplained heterogeneity leading to very low-certainty evidence. None of the included studies reported serious adverse events. Meta-analysis showed little to no difference in withdrawals due to adverse events between synbiotics (8/155) and placebo (1/147) (RR 4.58, 95% CI 0.80 to 26.19), or in any reported adverse events (3/96 versus 1/93, RR 2.88, 95% CI 0.32 to 25.92). These results are of very low certainty due to imprecision from the very low numbers of events and risk of bias. There were insufficient data to analyse by subgroups of specific functional abdominal pain syndrome (irritable bowel syndrome, functional dyspepsia, abdominal migraine, functional abdominal pain - not otherwise specified) or by specific strain of probiotic. There was insufficient evidence on school performance or change in school performance/attendance, social and psychological functioning, or quality of life to draw conclusions about the effects of probiotics or synbiotics on these outcomes.
AUTHORS' CONCLUSIONS
The results from this review demonstrate that probiotics and synbiotics may be more efficacious than placebo in achieving treatment success, but the evidence is of low certainty. The evidence demonstrates little to no difference between probiotics or synbiotics and placebo in complete resolution of pain. We were unable to draw meaningful conclusions about the impact of probiotics or synbiotics on the frequency and severity of pain as the evidence was all of very low certainty due to significant unexplained heterogeneity or imprecision. There were no reported cases of serious adverse events when using probiotics or synbiotics amongst the included studies, although a review of RCTs may not be the best context to assess long-term safety. The available evidence on adverse effects was of very low certainty and no conclusions could be made in this review. Safety will always be a priority in paediatric populations when considering any treatment. Reporting of all adverse events, adverse events needing withdrawal, serious adverse events and, particularly, long-term safety outcomes are vital to meaningfully move forward the evidence base in this field. Further targeted and appropriately designed RCTs are needed to address the gaps in the evidence base. In particular, appropriate powering of studies to confirm the safety of specific strains not yet investigated and studies to investigate long-term follow-up of patients are both warranted.
Topics: Humans; Child; Child, Preschool; Adolescent; Inulin; Probiotics; Irritable Bowel Syndrome; Abdominal Pain; Treatment Outcome
PubMed: 36799531
DOI: 10.1002/14651858.CD012849.pub2 -
Nutrients May 2022Functional dyspepsia represents one of the most common and prevalent disorders of the brain-gut interaction, with a large number of widespread risk factors being...
Functional dyspepsia represents one of the most common and prevalent disorders of the brain-gut interaction, with a large number of widespread risk factors being identified. With an intricate pathogenesis and symptomatology, it heavily impacts the quality of life and, due to the limited efficacy of traditional pharmacological agents, patients are likely to seek other medical and non-medical solutions to their problem. Over the last few years, significant research in this domain has emphasized the importance of various psychological therapies and nutritional recommendations. Nevertheless, a correlation has been established between functional dyspepsia and food intolerances, with more and more patients adopting different kinds of exclusion diets, leading to weight loss, restrictive eating behaviour and an imbalanced nutritional state, further negatively impacting their quality of life. Thus, in this systematic review, we aimed at analysing the impact and efficiency of certain exclusion diets undertook by patients, more precisely, the gluten-free diet and the low-FODMAP diet.
Topics: Diet Therapy; Diet, Carbohydrate-Restricted; Diet, Gluten-Free; Dyspepsia; Food Intolerance; Humans; Quality of Life
PubMed: 35631198
DOI: 10.3390/nu14102057 -
Cureus Dec 2021Functional dyspepsia is a common gastrointestinal disorder characterized by postprandial fullness or early satiety and epigastric burning or pain in the absence of... (Review)
Review
Functional dyspepsia is a common gastrointestinal disorder characterized by postprandial fullness or early satiety and epigastric burning or pain in the absence of organic disease. Acotiamide is a novel prokinetic motility drug being used in functional dyspepsia. Databases like PubMed, PubMed Central, Embase, and Scopus were searched for studies comparing the use of acotiamide and placebo for people with functional dyspepsia. Quantitative synthesis was performed using RevMan 5.4 (Cochrane, London, United Kingdom). The improvement in symptoms of functional dyspepsia after treatment was higher in people treated with acotiamide than placebo, although not statistically significant (OR, 1.48; 95% CI, 0.93 to 2.35; n = 1697; I = 59%). Among the commonly reported adverse effects, namely, raised in serum prolactin (OR 1.02, 95% CI 0.64 to 1.61; n = 1709; I = 44%), raised in alanine transaminase (OR 1.27, 95% CI 0.70 to 2.33; n = 1709; I = 0%), and raised in serum bilirubin (OR, 0.98; 95% CI, 0.52 to 1.87; I = 0%) did not differ between two groups. Acotiamide seems to be a promising agent in functional dyspepsia. However, further larger studies are needed to evaluate the role of acotiamide in functional dyspepsia.
PubMed: 35070565
DOI: 10.7759/cureus.20532 -
Archives of Iranian Medicine Jul 2021Dyspepsia is a highly prevalent gastrointestinal problem. The present study was carried out to assess the prevalence of dyspepsia in Iran. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dyspepsia is a highly prevalent gastrointestinal problem. The present study was carried out to assess the prevalence of dyspepsia in Iran.
METHODS
The present study was registered at PROSPERO with the code CRD42019148610. It was carried out based on MOOSE and reporting was performed according to the PRISMA protocol. Systematic search of the literature was performed in July 2019 on international databases of PubMed/Medline, Web of Science (ISI), Cochrane Library, EBSCO, CINAHL, EMBASE, Scopus, Science Direct, and local databases as well as the Google Scholar search engine. Heterogeneity was evaluated using I2 and Chi-square tests. All analyses were done using Comprehensive Meta-Analysis software.
RESULTS
Overall, 14 studies with a sample size of 54,118 subjects entered in this meta-analysis. The prevalence of dyspepsia in Iran was 14.6% (95% CI: 9.6-21.7). Large heterogeneity was detected among studies (I2=99.62%, <0.001). The prevalence of dysmotility-like, ulcer-like, and unspecified dyspepsia was estimated to be 9.7% (95% CI: 4.9-18.4), 12.1% (95% CI: 5.2-25.7) and 17.0% (95% CI: 7.8-33.4), respectively. The prevalence of dyspepsia in Iranian men and women was found at 11.1% (95% CI: 6.3-18.8) and 17.8% (95% CI: 10.0-29.7), respectively.
CONCLUSION
The prevalence of dyspepsia in Iran is relatively high. However, it is lower than global estimates.
Topics: Databases, Factual; Dyspepsia; Humans; Iran; Prevalence
PubMed: 34488322
DOI: 10.34172/aim.2021.80