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Annals of Medicine 2023The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms... (Meta-Analysis)
Meta-Analysis
PURPOSE
The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs).
METHODS
A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules.
RESULTS
A total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (, , , , , and ) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer.
CONCLUSIONS
The results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.
Topics: Humans; Gastritis, Atrophic; Molecular Docking Simulation; Network Pharmacology; Plant Extracts
PubMed: 38170849
DOI: 10.1080/07853890.2023.2299352 -
The Cochrane Database of Systematic... Jun 2023One-third of people with gastrointestinal disorders, including functional dyspepsia, use some form of complementary and alternative medicine, including herbal medicines. (Review)
Review
BACKGROUND
One-third of people with gastrointestinal disorders, including functional dyspepsia, use some form of complementary and alternative medicine, including herbal medicines.
OBJECTIVES
The primary objective is to assess the effects of non-Chinese herbal medicines for the treatment of people with functional dyspepsia.
SEARCH METHODS
We searched the following electronic databases on 22 December 2022: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Allied and Complementary Medicine Database, Latin American and Caribbean Health Sciences Literature, among other sources, without placing language restrictions.
SELECTION CRITERIA
We included RCTs comparing non-Chinese herbal medicines versus placebo or other treatments in people with functional dyspepsia.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened references, extracted data and assessed the risk of bias from trial reports. We used a random-effects model to calculate risk ratios (RRs) and mean differences (MDs). We created effect direction plots when meta-analysis was not possible, following the reporting guideline for Synthesis without Meta-analysis (SWiM). We used GRADE to assess the certainty of the evidence (CoE) for all outcomes.
MAIN RESULTS
We included 41 trials with 4477 participants that assessed 27 herbal medicines. This review evaluated global symptoms of functional dyspepsia, adverse events and quality of life; however, some studies did not report these outcomes. STW5 (Iberogast) may moderately improve global symptoms of dyspepsia compared with placebo at 28 to 56 days; however, the evidence is very uncertain (MD -2.64, 95% CI -4.39 to -0.90; I = 87%; 5 studies, 814 participants; very low CoE). STW5 may also increase the improvement rate compared to placebo at four to eight weeks' follow-up (RR 1.55, 95% CI 0.98 to 2.47; 2 studies, 324 participants; low CoE). There was little to no difference in adverse events for STW5 compared to placebo (RR 0.92, 95% CI 0.52 to 1.64; I = 0%; 4 studies, 786 participants; low CoE). STW5 may cause little to no difference in quality of life compared to placebo (no numerical data available, low CoE). Peppermint and caraway oil probably result in a large improvement in global symptoms of dyspepsia compared to placebo at four weeks (SMD -0.87, 95% CI -1.15 to -0.58; I = 0%; 2 studies, 210 participants; moderate CoE) and increase the improvement rate of global symptoms of dyspepsia (RR 1.53, 95% CI 1.30 to 1.81; I = 0%; 3 studies, 305 participants; moderate CoE). There may be little to no difference in the rate of adverse events between this intervention and placebo (RR 1.56, 95% CI 0.69 to 3.53; I = 47%; 3 studies, 305 participants; low CoE). The intervention probably improves the quality of life (measured on the Nepean Dyspepsia Index) (MD -131.40, 95% CI -193.76 to -69.04; 1 study, 99 participants; moderate CoE). Curcuma longa probably results in a moderate improvement global symptoms of dyspepsia compared to placebo at four weeks (MD -3.33, 95% CI -5.84 to -0.81; I = 50%; 2 studies, 110 participants; moderate CoE) and may increase the improvement rate (RR 1.50, 95% CI 1.06 to 2.11; 1 study, 76 participants; low CoE). There is probably little to no difference in the rate of adverse events between this intervention and placebo (RR 1.26, 95% CI 0.51 to 3.08; 1 study, 89 participants; moderate CoE). The intervention probably improves the quality of life, measured on the EQ-5D (MD 0.05, 95% CI 0.01 to 0.09; 1 study, 89 participants; moderate CoE). We found evidence that the following herbal medicines may improve symptoms of dyspepsia compared to placebo: Lafonesia pacari (RR 1.52, 95% CI 1.08 to 2.14; 1 study, 97 participants; moderate CoE), Nigella sativa (SMD -1.59, 95% CI -2.13 to -1.05; 1 study, 70 participants; high CoE), artichoke (SMD -0.34, 95% CI -0.59 to -0.09; 1 study, 244 participants; low CoE), Boensenbergia rotunda (SMD -2.22, 95% CI -2.62 to -1.83; 1 study, 160 participants; low CoE), Pistacia lenticus (SMD -0.33, 95% CI -0.66 to -0.01; 1 study, 148 participants; low CoE), Enteroplant (SMD -1.09, 95% CI -1.40 to -0.77; 1 study, 198 participants; low CoE), Ferula asafoetida (SMD -1.51, 95% CI -2.20 to -0.83; 1 study, 43 participants; low CoE), ginger and artichoke (RR 1.64, 95% CI 1.27 to 2.13; 1 study, 126 participants; low CoE), Glycyrrhiza glaba (SMD -1.86, 95% CI -2.54 to -1.19; 1 study, 50 participants; moderate CoE), OLNP-06 (RR 3.80, 95% CI 1.70 to 8.51; 1 study, 48 participants; low CoE), red pepper (SMD -1.07, 95% CI -1.89 to -0.26; 1 study, 27 participants; low CoE), Cuadrania tricuspidata (SMD -1.19, 95% CI -1.66 to -0.72; 1 study, 83 participants; low CoE), jollab (SMD -1.22, 95% CI -1.59 to -0.85; 1 study, 133 participants; low CoE), Pimpinella anisum (SMD -2.30, 95% CI -2.79 to -1.80; 1 study, 107 participants; low CoE). The following may provide little to no difference compared to placebo: Mentha pulegium (SMD -0.38, 95% CI -0.78 to 0.02; 1 study, 100 participants; moderate CoE) and cinnamon oil (SMD 0.38, 95% CI -0.17 to 0.94; 1 study, 51 participants; low CoE); moreover, Mentha longifolia may increase dyspeptic symptoms (SMD 0.46, 95% CI 0.04 to 0.88; 1 study, 88 participants; low CoE). Almost all the studies reported little to no difference in the rate of adverse events compared to placebo except for red pepper, which may result in a higher risk of adverse events compared to placebo (RR 4.31, 95% CI 1.56 to 11.89; 1 study, 27 participants; low CoE). With respect to the quality of life, most studies did not report this outcome. When compared to other interventions, essential oils may improve global symptoms of dyspepsia compared to omeprazole. Peppermint oil/caraway oil, STW5, Nigella sativa and Curcuma longa may provide little to no benefit compared to other treatments.
AUTHORS' CONCLUSIONS
Based on moderate to very low-certainty evidence, we identified some herbal medicines that may be effective in improving symptoms of dyspepsia. Moreover, these interventions may not be associated with important adverse events. More high-quality trials are needed on herbal medicines, especially including participants with common gastrointestinal comorbidities.
Topics: Humans; Dyspepsia; Quality of Life; Plant Extracts; Complementary Therapies
PubMed: 37323050
DOI: 10.1002/14651858.CD013323.pub2 -
Expert Reviews in Molecular Medicine Aug 2023Metallic nanoparticles from different natural sources exhibit superior therapeutic options as compared to the conventional methods. species have attracted special... (Review)
Review
BACKGROUND
Metallic nanoparticles from different natural sources exhibit superior therapeutic options as compared to the conventional methods. species have attracted special attention of researchers worldwide due to the presence of bioactive molecules such as flavonoids, biflavonoids, triterpenes, steroids, saponins, tannins and other secondary metabolites that exhibit antimicrobial, antiplasmodial, anticancer and anti-inflammatory activities. Environment friendly green synthesised silver nanoparticles from species provide viable, safe and efficient treatment against different fungal pathogens.
OBJECTIVE
This systematic review aims to summarise the literature pertaining to superior antifungal ability of green synthesised silver nanoparticles using plant extracts of spp. in comparison to both aqueous and ethanolic raw plant extracts by electronically collecting articles from databases.
METHODS
The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis were taken into consideration while preparing this review. The titles and abstracts of the collected data were stored in Endnote20 based on the inclusion and exclusion criteria. The search strategy included literature from established sources like PubMed, Google Scholar and Retrieval System Online using subject descriptors.
RESULTS
The search yielded 60 articles with unique hits. After removal of duplications, 46 articles were identified, 40 were assessed and only seven articles were chosen and included in this review based on our eligibility criteria.
CONCLUSION
The physicochemical and preliminary phytochemical investigations of suggest higher drug potency of nanoparticles synthesised from plant extract against different diseases as compared to aqueous and ethanolic plant extracts. The study holds great promise as the synthesis of nanoparticles involves low energy consumption, minimal technology and least toxic effects.
Topics: Humans; Metal Nanoparticles; Selaginellaceae; Silver; Anti-Infective Agents; Plant Extracts
PubMed: 37534437
DOI: 10.1017/erm.2023.21 -
Virology Journal May 2022The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant extracts or plant-derived compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question, which herbal compound has been more effective?
MAIN BODY
The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was done. Quality control of articles was performed. Data analysis was carried out in STATA software.
CONCLUSION
Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds that had the greatest effect on virus inhibition, Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV-2. Our study confirmed insufficient data to support alkaloid compounds against SARS-COV-2, and the small number of studies that used alkaloid compounds was a limitation. It is recommended to investigate the effect of more alkaloid compounds against Corona virus.
Topics: Alkaloids; Antiviral Agents; Humans; Plant Extracts; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35597998
DOI: 10.1186/s12985-022-01808-z -
The Cochrane Database of Systematic... Mar 2016Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease that develops in a limb during exercise and is relieved with rest. Most drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease that develops in a limb during exercise and is relieved with rest. Most drug treatments of IC have a limited effect in improving walking distance. Padma 28, a Tibetan herbal preparation, has been used to treat IC, but there is debate as to whether Padma 28 produces a clinical benefit beyond the placebo effect. This is an update of a review first published in 2013.
OBJECTIVES
To determine whether Padma 28 is effective, compared with placebo or other medications, in increasing pain-free and maximum walking distance for patients with intermittent claudication.
SEARCH METHODS
For this update the Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (September 2015), the Cochrane Register of Studies ((CENTRAL) (2015, Issue 8)) and clinical trials databases.
SELECTION CRITERIA
Randomised controlled trials of Padma 28 compared with placebo or other pharmacological treatments in people suffering from IC.
DATA COLLECTION AND ANALYSIS
All review authors independently assessed the selected studies and extracted the data. Risk of bias was evaluated independently by two review authors. Depending on the data provided in the individual trials, we extracted mean or median walking distance at the end of the trial, or change in walking distance over the course of the trial, or both. Where not provided, and whenever possible, the statistical significance of differences in these parameters between treatment and placebo groups in individual trials was calculated. Where possible, data were combined by meta-analysis.
MAIN RESULTS
No new trials were identified in the search for this review update. In total five trials involving 365 participants were included in this review. All trials compared Padma 28 with placebo for at least 16 weeks of follow-up. Pain-free and maximum walking distances both increased significantly in the groups treated with Padma 28, with no significant change in the placebo group. In general, the studies presented results comparing the treatment arms before and after treatment but made no comparisons between the Padma 28 and placebo groups. Pooled data of maximum walking distance after treatment with Padma 28 and placebo from two studies (193 participants) indicated a higher maximum walking distance (mean difference (MD) 95.97 m, 95% confidence interval (CI) 79.07 m to 112.88 m, P < 0.00001, very low quality evidence) in the Padma 28 group compared with placebo. The clinical importance of these observed changes in walking distance is unclear as no quality of life data were reported. There was no effect on ankle brachial index (ABI): change in ABI values between baseline and six months follow up MD -0.01, 95% CI -0.07 to 0.05, 1 study, 56 participants, P = 0.72, very low quality evidence). Mild side effects, especially gastrointestinal discomfort, tiredness and skin eruption, were reported but this outcome was not different between the Padma 28 and placebo groups (odds ratio 1.09, 95% CI 0.42 to 2.83, four studies, 231 participants, P = 0.86, very low quality evidence).
AUTHORS' CONCLUSIONS
Some evidence exists from individual trials to suggest that Padma 28 may be effective in increasing walking distances, at least in the short term (four months), in people with IC. Side effects do not appear to be a problem. However, the longer term effects of treatment are unknown and the clinical significance of the improvements in walking distance are questionable. Moreover, the quality of the evidence is limited by the small sample size of the available trials, limited reporting of statistical analyses that compared treatment groups, and relatively high withdrawal rates that were linked to the outcome. That is, patients were withdrawn if they failed to improve walking distance. There was also evidence of publication bias. We therefore feel there is currently insufficient evidence to draw conclusions regards the effectiveness of Padma 28 in the routine management of IC. Further well-designed research would be required to determine the true effects of this herbal preparation.
Topics: Humans; Intermittent Claudication; Placebo Effect; Plant Extracts; Randomized Controlled Trials as Topic; Time Factors; Walking
PubMed: 27021597
DOI: 10.1002/14651858.CD007371.pub3 -
Frontiers in Immunology 2023To systematically evaluate the clinical efficacy and safety of sublingual immunotherapy for allergic rhinitis (AR) and provide evidence for clinical treatment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the clinical efficacy and safety of sublingual immunotherapy for allergic rhinitis (AR) and provide evidence for clinical treatment.
METHODS
A literature search was performed on the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Web of Science, Cochrane Library, and Embase database. Data from randomized controlled trials (RCTs) of sublingual immunotherapy for AR were screened and extracted from the establishment of those databases to November 2022. Subsequently, a network meta-analysis was performed using a statistical software R 4.2.
RESULTS
Totally 22 RCTs that met the inclusion and exclusion criteria and screened from 1,164 literature were included. A total of 4,941 AR patients were involved in the 22 trials, as well as five interventions including placebo, pharmacotherapy, subcutaneous immunotherapy_dust mite, sublingual immunotherapy_dust mite, and sublingual immunotherapy_ grass mix plus pollen extract. The results of network meta-analysis showed that, based on symptom scores after different interventions for AR, the most effective treatments for AR were in order as follows: sublingual immunotherapy_dust mite, subcutaneous immunotherapy_dust mite, sublingual immunotherapy_ grass mix plus pollen extract, placebo, and pharmacotherapy. Importantly, sublingual immunotherapy had fewer adverse reactions and higher safety.
CONCLUSION
Sublingual immunotherapy_dust mite for AR has the best efficacy, whereas traditional medicine has the worst. More high-quality studies with a large sample and multiple centers are needed to verify this conclusion in the future, so as to further provide more reliable evidence-based medical evidence for the clinical treatment options of AR patients.
Topics: Animals; Humans; Sublingual Immunotherapy; Network Meta-Analysis; Rhinitis, Allergic; Pyroglyphidae; Plant Extracts
PubMed: 37063866
DOI: 10.3389/fimmu.2023.1144816 -
Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.International Journal of Toxicology 2024The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main... (Review)
Review
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.
Topics: Banisteriopsis; Humans; N,N-Dimethyltryptamine; Animals; Plant Extracts; Harmine; Harmaline
PubMed: 38363085
DOI: 10.1177/10915818241230916 -
Frontiers in Endocrinology 2023The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in men and to observe the effect of PAL combined therapy on sexual function in patients with erectile dysfunction (ED), and we hope to provide more choices of drugs for treating patients with ED.
METHODS AND ANALYSIS
The study was constructed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched seven databases from inception to 15 February 2023, for a comprehensive search of clinical trials using relevant keywords. Continuous variables in this meta-analysis were calculated using the mean difference and 95% confidence interval. All relevant statistical analyses were performed using RevMan v. 5.4 software.
RESULTS
Three studies with 184 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. The results of the current meta-analysis showed that there were significant differences in the international index of erectile function scores (erectile domain), intercourse satisfaction scores, orgasmic function scores, overall satisfaction scores, and sexual desire scores between the combination treatment group and the control group. There was no significant difference in improving the testosterone levels between the two groups.
CONCLUSION
These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED. This study will provide clinicians with more options for treating patients with ED. More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#myprosperoUnique, Identifier: CRD42023411781.
Topics: Humans; Male; Erectile Dysfunction; Plant Extracts; Flavonoids; Arginine
PubMed: 37908749
DOI: 10.3389/fendo.2023.1211720 -
BioMed Research International 2022or Tongkat Ali (family: Simaroubaceae) has the potential to be utilised as an antimicrobial and antiparasitic agent that correlated with its traditional use to treat... (Review)
Review
or Tongkat Ali (family: Simaroubaceae) has the potential to be utilised as an antimicrobial and antiparasitic agent that correlated with its traditional use to treat jaundice, malaria, antiseptic agent, and many more. This review is aimed at systematically sieving through articles regarding the antimicrobial and antiparasitic activity of . A total of 123 studies have been found using suitable keywords and manually searched from previous studies through the four databases. After title screening and abstract examination, 56 articles were excluded due to duplication and not meeting the acceptance criteria. 67 articles were assessed on full-text accessibility, 31 studies remained, and this number decreased to 20 articles after a careful examination of the full-text articles. Among the 20 articles selected, 17 articles proved the potential of as an antimicrobial and antiparasitic agent efficiently. 2 selected articles showed partial positive results, which specified specific microorganisms tested. In contrast, another 1 article gave a completely negative result. As for the conclusion, current studies highlighted by this review may shed light on the future direction of studies concerning as a novel antimicrobial and antiparasitic agent. However, more research should be done in the future focusing on the efficiency of for veterinary medicine utilisation.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antiparasitic Agents; Eurycoma; Plant Extracts; Plant Roots
PubMed: 35845951
DOI: 10.1155/2022/4999797 -
The Cochrane Database of Systematic... Apr 2016Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005.
OBJECTIVES
To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI.
SEARCH METHODS
For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015).
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses.
MAIN RESULTS
We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events.
AUTHORS' CONCLUSIONS
Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.
Topics: 4-Aminobenzoic Acid; Calcium Dobesilate; Centella; Chronic Disease; Diosmin; Edema; Hematologic Agents; Humans; Leg Ulcer; Phytotherapy; Pinus; Plant Extracts; Randomized Controlled Trials as Topic; Rutin; Venous Insufficiency; para-Aminobenzoates
PubMed: 27048768
DOI: 10.1002/14651858.CD003229.pub3