INTRODUCTION: Liver conditions are major burdens upon health systems around the world. Turmeric /curcumin is believed to possess therapeutic features in ameliorating various metabolic disorders. In this systematic review and meta-analysis of the randomized controlled trials (RCTs), we examined the effect of turmeric/curcumin supplementation on some liver function tests (LFTs).
METHODS: We comprehensively searched online databases (i.e. PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar) from inception up to October 2022. Final outcomes included aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Weighted mean differences (WMDs) were reported. In case of between-study heterogeneity, subgroup analysis was conducted. Non-linear dose-response analysis was carried out to detect the potential effect of dosage and duration. The registration code is CRD42022374871.
RESULTS: Thirty-one RCTs were included in the meta-analysis. Turmeric/curcumin supplementation significantly reduced blood levels of ALT (WMD = -4.09 U/L; 95 % CI = -6.49, -1.70) and AST (WMD = -3.81 U/L; 95 % CI = -5.71, -1.91), but not GGT (WMD: -12.78 U/L; 95 % CI: -28.20, 2.64). These improvements, though statistically significant, do not ensure clinical effectiveness.
CONCLUSION: It seems that turmeric/curcumin supplementation might be effective in improving AST and ALT levels. However, further clinical trials are needed to examine its effect on GGT. Quality of the evidence across the studies was low for AST and ALT and very low for GGT. Therefore, more studies with high quality are needed to assess this intervention on hepatic health.
OBJECTIVE: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA).
METHODS: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software.
RESULTS: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events.
CONCLUSION: Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.
OBJECTIVE: This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis.
PATIENTS AND METHODS: Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome.
RESULTS: Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%).
CONCLUSIONS: Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.
OBJECTIVE: To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) against placebo and active controls for improving pain and physical function of patients with knee osteoarthritis (OA). We hypothesize that topical NSAIDs will be safe and effective for relieving symptoms in patients with knee OA.
METHODS: The authors performed a systematic review according to the PRISMA guidelines, searching PubMed, EMBASE, and Cochrane databases. Randomized control trials that investigated topical NSAIDs that are widely available in many countries against both placebo and active controls in primary knee osteoarthritis were included. Studies that investigated other treatment modalities or treated nonspecific OA were excluded. A meta-analysis was performed to quantify the effect sizes and heterogeneity of the NSAIDs used.
RESULTS: Upon initial search, 259 records were identified with 18 studies remaining after duplicate removal, abstract, and full text screening. All NSAIDs demonstrated statistically significant reduction in at least one parameter of OA symptoms. The majority of included studies (66.7%) evaluated diclofenac. In the meta-analysis, standardized mean differences (SMD) of topical NSAIDs versus placebo were calculated and interpreted as having moderate effect size for improvement in pain (0.365, 95% confidence interval (CI) 0.240, 0.490) and physical function (0,354, 95% CI 0.268, 0.493). With regards to safety, studies that used patches or dimethyl sulfoxide (DMSO) in the carrier reported a higher incidence of adverse events (AEs) than other carriers. Skin AEs were higher in the treatment group than the placebo group and gastrointestinal AEs were lower in the treatment group than placebo.
CONCLUSION: Topical diclofenac and ketoprofen are the most rigorously studied topical NSAIDs in the treatment of knee OA and have demonstrated the most significant reduction in pain and improvement of function. Ibuprofen was effective for pain relief and physical function improvement, but more high-powered studies are needed to make a confident comparison of efficacy. Additionally, the "carrier" used to deliver the topical NSAID has an impact on the adverse event profile. This has safety implications for prescribers and pharmaceutical development. Topical diclofenac is widely available internationally and is the only topical NSAID approved for over the counter use in the US. It should be recommended to patients as a first line conservative management for OA of the knee.
Key indexing terms: "knee osteoarthritis", "administration, topical drug", "agents, non-steroidal anti-inflammatory", "osteoarthritis", "diclofenac", "ketoprofen".
OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN: Systematic review and network meta-analysis of randomised trials.
DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.
OBJECTIVE: Current global guidelines regarding the first-line analgesics (acetaminophen, topical or oral non-steroidal anti-inflammatory drugs [NSAIDs]) for knee osteoarthritis remain controversial and their comparative risk-benefit profiles have yet to be adequately assessed.
DESIGN: Pubmed, Embase, Cochrane Library, and Web of Science were searched from database inception to March 2021 for randomized controlled trials (RCTs) comparing acetaminophen, topical NSAIDs and oral NSAIDs directly or indirectly in knee osteoarthritis. Bayesian network meta-analyses were conducted. A propensity-score matched cohort study was also conducted among patients with knee osteoarthritis in The Health Improvement Network database.
RESULTS: 122 RCTs (47,113 participants) were networked. Topical NSAIDs were superior to acetaminophen (standardized mean difference [SMD]=-0.29, 95% credible interval [CrI]: -0.52 to -0.06) and not statistically different from oral NSAIDs (SMD=0.03, 95% CrI: -0.16 to 0.22) for function. It had lower risk of gastrointestinal adverse effects (AEs) than acetaminophen (relative risk [RR]=0.52, 95%CrI: 0.35 to 0.76) and oral NSAIDs (RR=0.46, 95%CrI: 0.34 to 0.61) in RCTs. In real-world data, topical NSAIDs showed lower risks of all-cause mortality (hazard ratio [HR]=0.59, 95% confidence interval [CI]: 0.52 to 0.68), cardiovascular diseases (HR=0.73, 95%CI: 0.63 to 0.85) and gastrointestinal bleeding (HR=0.53, 95%CI: 0.41 to 0.69) than acetaminophen during the one-year follow-up (n=22,158 participants/group). A better safety profile was also observed for topical than oral NSAIDs (n=14,218 participants/group).
CONCLUSIONS: Topical NSAIDs are more effective than acetaminophen but not oral NSAIDs for function improvement in people with knee osteoarthritis. Topical NSAIDs are safer than acetaminophen or oral NSAIDs in trials and real-world data.
OBJECTIVE: Despite an extensive body of research on NSAIDs in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.
METHODS: We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. RCTs assessing the efficacy and/or safety of FDA-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences and risk ratios with 95% confidence intervals.
RESULTS: We included 72 RCTs (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [-0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of GI AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [1.21, 1.57]). The incidence of CV AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.
CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen. This article is protected by copyright. All rights reserved.
OBJECTIVE: Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.METHODS: We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).RESULTS: We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.
