-
Neurogastroenterology and Motility Feb 2023Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response.
METHODS
We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined.
KEY RESULTS
We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms.
CONCLUSIONS AND INFERENCES
The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
Topics: Adult; Humans; Dyspepsia; Placebo Effect; Treatment Outcome
PubMed: 36168188
DOI: 10.1111/nmo.14474 -
Therapeutic Advances in Gastroenterology 2022Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.
BACKGROUND
Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.
OBJECTIVES
To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID.
DESIGN
A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed.
DATA SOURCES AND METHODS
Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages 'meta' and 'metafor'.
RESULTS
A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06-0.22, = 99%] and 0.22 (95% CI, 0.10-0.41, = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04-0.38, = 96%), 0.06 (95% CI, 0.03-0.11, = 98%), 0.20 (95% CI, 0.08-0.43, = 98%), and 0.17 (95% CI, 0.10-0.27, = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04-0.23, = 98%), 0.20 (95% CI, 0.06-0.50, = 97%), and 0.17 (95% CI, 0.06-0.37, = 96%), respectively.
CONCLUSION
GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.
PubMed: 36004306
DOI: 10.1177/17562848221118403 -
Frontiers in Pharmacology 2023The demand for complementary and alternative medicine for the management of functional dyspepsia (FD) is increasing due to the insufficient efficacy of conventional...
The demand for complementary and alternative medicine for the management of functional dyspepsia (FD) is increasing due to the insufficient efficacy of conventional treatment options. In Asia, the Chinese herbal medicine formula (BXT) has been used to treat FD. We searched 11 digital medical databases on 1 September 2021. Randomized controlled trials (RCTs) that investigated the efficacy of BXT or combination therapy (BXT plus Western medicines) for FD were selected. The outcome parameters were total clinical efficacy rate (TCE), motilin level, symptom checklist-90-revised (SCL-90-R), and visual analog scale (VAS) for dyspepsia and adverse events. Cochrane risk of bias tool 2.0 (RoB 2) was used for the quality assessment of included studies. The meta-analysis comprised 57 RCTs with 5,525 participants. BXT was more efficacious, with a higher TCE than Western medicine. Combination therapy (BXT plus Western medicine) also resulted in a higher TCE than Western medicine. Combination therapy improved motilin levels and psychological symptoms to a greater extent than Western medicine, evidenced by a higher SCL-90-R score. However, no significant difference in VAS scores was observed between the BXT and placebo groups. BXT and combination therapy were associated with fewer adverse events than Western medicine or placebo. Our findings suggest that BXT and its combination therapy may be an effective and safe alternative treatment for FD. More RCTs with better methodologies are required to strengthen this evidence. [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019123285], identifier [CRD42019123285].
PubMed: 37274096
DOI: 10.3389/fphar.2023.1130257 -
Medicine Feb 2020Functional dyspepsia (FD) is a functional gastrointestinal disorder. Evidence suggests that disturbance of the gastrointestinal microbiota may be implicated in FD. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional dyspepsia (FD) is a functional gastrointestinal disorder. Evidence suggests that disturbance of the gastrointestinal microbiota may be implicated in FD. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics and probiotics for FD.
METHODS
MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (through September 2018). Randomized controlled trials (RCTs) that recruited adults with FD and that compared prebiotics, probiotics, or synbiotics with placebo or no therapy were eligible. Eligibility assessment and data extraction were performed by two independent researchers. Dichotomous symptom data were pooled to obtain a relative risk (RR) with a 95% confidence interval (CI) of remaining symptomatic after therapy. Continuous data were pooled using a standardized or weighted mean difference with a 95% CI.
RESULTS
The search strategy identified 1062 citations. Five RCTs were eligible for inclusion. The RR of FD symptoms improving with probiotics or probiotics vs placebo was 1.15 (95% CI 1.01-1.30). Probiotics and prebiotics had beneficial effects on symptom scores of FD. Data for synbiotics in the context of FD were sparse, and no definite conclusions could be drawn.
ETHICS AND DISSEMINATION
This study belongs to the category of systematic reviews, not clinical trials. Therefore, it does not require ethical approval. The results of this study will be published in influential international academic journals related to this topic.
CONCLUSION
Probiotics and prebiotics seemed to be effective treatments for FD, although the individual species and strains that are the most beneficial remain unclear. Using only probiotics failed to improve the symptoms of FD. Further evidence is required before the role of probiotics, prebiotics, and synbiotics in FD can be fully understood.
Topics: Adult; Dyspepsia; Female; Gastrointestinal Microbiome; Humans; Male; Prebiotics; Probiotics; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32049821
DOI: 10.1097/MD.0000000000019107 -
International Journal of Molecular... Apr 2024The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a... (Review)
Review
The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates of up to 20 million prescriptions per year in the US until 2035. This systematic review aims to assess the incidence of thyroid cancer and detail the spectrum of adverse events associated with semaglutide, focusing on its implications for patient care. Through a systematic search of PubMed, Scopus, and Embase databases up to December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, with 7830 receiving semaglutide, were analyzed, with an additional number of 18 studies that were separately discussed because they reported data from the same RCTs. The review focused on thyroid cancer incidence, gastrointestinal symptoms, and other significant adverse events attributed to semaglutide. The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk. Adverse events were predominantly gastrointestinal, including nausea (2.05% to 19.95%) and diarrhea (1.4% to 13%). Nasopharyngitis and vomiting were also notable, with mean prevalences of 8.23% and 5.97%, respectively. Other adverse events included increased lipase levels (mean of 6.5%), headaches (mean prevalence of 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms (mean prevalence of 5.23%), dyspepsia (mean prevalence of 5.18%), and constipation (mean prevalence of 6.91%). Serious adverse events varied from 7% to 25.2%, highlighting the need for vigilant patient monitoring. These findings underscore the gastrointestinal nature of semaglutide's adverse events, which, while prevalent, did not significantly deter from its clinical benefits in the treatment landscape. This systematic review provides a comprehensive assessment of semaglutide's safety profile, with a focus on gastrointestinal adverse events and a low incidence of thyroid cancer. Despite the prevalence of gastrointestinal symptoms, semaglutide remains an efficacious option for managing diabetes and obesity. The detailed characterization of adverse events underscores the importance of monitoring and managing these effects in clinical practice, excluding the hypothesis of carcinogenesis.
Topics: Humans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Hypoglycemic Agents; Incidence; Obesity; Thyroid Neoplasms
PubMed: 38673931
DOI: 10.3390/ijms25084346 -
Antibiotics (Basel, Switzerland) Jan 2021The most recommended treatment for a infection is high doses of combined antibiotics. The objective of this article is to perform a systematic review of the economic... (Review)
Review
BACKGROUND
The most recommended treatment for a infection is high doses of combined antibiotics. The objective of this article is to perform a systematic review of the economic evaluation studies applied to assess the efficiency of diagnostic testing for infections, so that their main characteristics can be identified and to learn from the literature how the antimicrobial resistance (AMR) issue is incorporated into these economic evaluations.
METHODS
We conducted a systematic review to compare the costs and clinical effectiveness of diagnostic strategies for infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and extracted the items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.
RESULTS
We found thirteen articles that were of good quality according to CHEERS: six studies focused on diagnostics of infections associated with dyspepsia and four on duodenal ulcers. Testing was found to be the most cost-effective strategy in eight articles. Four studies considered AMR.
CONCLUSIONS
Testing was more cost-effective than empirical treatment, except in cases of high prevalence (as with developing countries) or when patients could be stratified according to their comorbidities. The introduction of AMR into the model may change the efficiency of the testing strategy.
PubMed: 33430005
DOI: 10.3390/antibiotics10010055 -
Gut Microbes 2024Interactions between diet and gastrointestinal microbiota influence health status and outcomes. Evaluating these relationships requires accurate quantification of...
Interactions between diet and gastrointestinal microbiota influence health status and outcomes. Evaluating these relationships requires accurate quantification of dietary variables relevant to microbial metabolism, however current dietary assessment methods focus on dietary components relevant to human digestion only. The aim of this study was to synthesize research on foods and nutrients that influence human gut microbiota and thereby identify knowledge gaps to inform dietary assessment advancements toward better understanding of diet-microbiota interactions. Thirty-eight systematic reviews and 106 primary studies reported on human diet-microbiota associations. Dietary factors altering colonic microbiota included dietary patterns, macronutrients, micronutrients, bioactive compounds, and food additives. Reported diet-microbiota associations were dominated by routinely analyzed nutrients, which are absorbed from the small intestine but analyzed for correlation to stool microbiota. Dietary derived microbiota-relevant nutrients are more challenging to quantify and underrepresented in included studies. This evidence synthesis highlights advancements needed, including opportunities for expansion of food composition databases to include microbiota-relevant data, particularly for human intervention studies. These advances in dietary assessment methodology will facilitate translation of microbiota-specific nutrition therapy to practice.
Topics: Humans; Diet; Gastrointestinal Microbiome; Gastrointestinal Tract; Nutrients
PubMed: 38725230
DOI: 10.1080/19490976.2024.2350785 -
Journal of Psychosomatic Research Dec 2023Cognitive behavioural therapy (CBT) is increasingly used to manage Disorders of Gut-Brain Interaction (DGBIs). This systematic review aimed to review the evidence for... (Review)
Review
OBJECTIVE
Cognitive behavioural therapy (CBT) is increasingly used to manage Disorders of Gut-Brain Interaction (DGBIs). This systematic review aimed to review the evidence for the effectiveness of CBT-based interventions for patients with gastroduodenal DGBIs.
METHODS
Medline, Embase, PubMed, Cochrane Central, and Scopus were searched in July 2022. Studies were included if they investigated the effects of a CBT-based intervention on gastrointestinal symptoms and/or psychological outcomes pre- and post-intervention in patients with gastroduodenal DGBIs. Case studies, studies not in English, and studies with patients under 18 years were excluded. Results were synthesised narratively, and standardised effect sizes were calculated where possible.
RESULTS
Nine studies (seven RCTs and two pre/post studies) were identified, with data reported in 10 articles (total N = 602). The studies investigated patients with functional dyspepsia (n = 7), rumination syndrome (n = 1), and supragastric belching (n = 1). The studies had heterogeneous interventions, methodologies, and outcomes, precluding meta-analysis, as well as a moderate-high risk of bias and high drop-outs rates. Findings demonstrated decreased gastrointestinal symptoms and improved anxiety, depression, and quality of life, from pre- to post-intervention, with medium to large effect sizes for symptoms and small to large effect sizes for psychological outcomes. Efficacy was maintained at follow-up, up to one year later.
CONCLUSIONS
This review suggests promising evidence that CBT effectively improves gastrointestinal symptoms and psychological outcomes in patients with gastroduodenal DGBIs. However, heterogeneity, risk of bias, and lack of statistical reporting were noted, indicating the need for more robust research and standardisation.
Topics: Adolescent; Humans; Anxiety Disorders; Brain; Cognitive Behavioral Therapy; Psychotherapy; Quality of Life
PubMed: 37832277
DOI: 10.1016/j.jpsychores.2023.111516 -
Frontiers in Medicine 2021We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of...
We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of evidence (QoE) of these findings. A total of 12 English, Korean, and Chinese databases were searched on December 18, 2020. Randomized controlled trials (RCTs) assessing the effectiveness of acupuncture as an add-on therapy to conventional WM for functional dyspepsia (FD) were included. The primary outcome was the symptom score of FD. The risk of bias of the included studies and QoE were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation method, respectively. A total of 22 RCTs were included. The total and individual FD symptom scores were significantly improved in the acupuncture combined with WM groups compared with the WM alone groups, except for in one study. The Nepean dyspepsia index score and total effective rate mostly improved significantly in the acupuncture group, regardless of the WM used and acupuncture type. FD-related biomarkers, such as ghrelin and gastrin levels, showed mixed results. The acupuncture group showed a significantly lower recurrence rate after 3-6 months of follow-up than the WM alone group. There were no differences in the incidence of adverse events between the two groups. The included studies generally had low methodological quality. The QoE for the main findings was generally very low to moderate. Limited evidence suggests that acupuncture has the potential to improve FD treatment in combination with conventional WM. Furthermore, the methodological quality of the included studies and QoE of the main findings were generally low. Therefore, RCTs with a rigorous methodology, including sham acupuncture and multiethnic subjects, should be performed. OSF registries [https://osf.io/mxren], PROSPERO [CRD42021226608].
PubMed: 34381798
DOI: 10.3389/fmed.2021.682783 -
Journal of Gastroenterology and... Jan 2021Functional dyspepsia (FD) is characterized by chronic and unexplained indigestion at upper abdomen. Because of unsatisfactory effect of conventional treatments, demand... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Functional dyspepsia (FD) is characterized by chronic and unexplained indigestion at upper abdomen. Because of unsatisfactory effect of conventional treatments, demand is growing for complementary and alternative medicine. Rikkunshito (RKT) is a herbal medicine, which has been widely used for FD in Asia; however, the evidence is lacking. We carried out systematic review and meta-analysis to evaluate the effect and safety of RKT in the treatment of FD.
METHODS
Electronic databases were searched in April 2019, including PUBMED, EMBASE, and Cochrane Library. All eligible studies should be randomized controlled trials (RCTs) comparing RKT or combination therapy (RKT and western medicine) group to western medicine group. The primary outcome measure was the total clinical efficacy rate (TCE). The secondary outcomes were total dyspepsia symptom scale, gastric emptying rate, gastrin, motilin, recurrence 6 months after treatment, and Hamilton depression rating scale.
RESULTS
Fifty-two RCTs with 5475 patients were involved in this systematic review and meta-analysis. Compared with western medicine, RKT showed significant better result, with higher TCE (relative risk = 1.21, 95% confidence interval 1.17 to 1.25, P < 0.001). RKT presented higher reduction of total dyspepsia symptom scale, more improved gastric emptying rate, and lower recurrence 6 months after treatment compared with western medicine. However, there was no significant difference in Hamilton depression rating scale between RKT and western medicine group. Combination therapy brought significant symptom improvement with TCE compared with western medicine alone.
CONCLUSIONS
Rikkunshito and combination therapy might be considered an effective alternative treatment for FD. Further rigorously designed and high-quality RCTs are needed.
Topics: Drug Therapy, Combination; Drugs, Chinese Herbal; Dyspepsia; Female; Gastric Emptying; Humans; Male; Phytotherapy; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome
PubMed: 32767596
DOI: 10.1111/jgh.15208