Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria?

Background Previous reviews of the diagnosis for rheumatoid arthritis (RA) have not compared anti-mutated citrullinated vimentin (MCV) with anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) in respect of sensitivity, specificity and the area under the curve (AUC) against disease controls for differential diagnosis. This meta-analysis aims to evaluate the value of anti-MCV in the diagnosis for RA, the combined sensitivity of anti-MCV and anti-CCP, and certain clinical characteristics related to the performance of anti-MCV. Methods Medline, Embase, Cochrane Library and Web of Science were searched for articles published up to 25 August 2018. A total of 33 studies including 6044 RA patients and 5094 healthy or disease controls achieved inclusive criteria. QUADAS-2 was applied to evaluate the quality of the included studies. The bivariate random effects model was employed in primary data synthesis to evaluate the diagnostic performance. Results The sensitivity of anti-MCV, anti-CCP and RF in RA diagnosis against a disease control group was 0.71, 0.71, 0.77, with the specificity of 0.89, 0.95, 0.73, and the AUC of the SROC of 0.89, 0.95, 0.82, respectively. The predesign of the primary study and diagnostic criteria were statistically significant as sources of heterogeneity. Anti-MCV and anti-CCP tests demonstrated a sensitivity of 0.77 when performed in parallel, with a sensitivity of 0.60 when performed in series; whereas, the combination of anti-MCV and RF presented a sensitivity of 0.64 when used in series. Conclusions Anti-MCV demonstrates comparable diagnostic value to anti-CCP and RF, thus it can be an effective diagnostic marker for RA and may be written into the next authoritative criteria.

Edaravone for Acute Ischemic Stroke: A Systematic Review and Meta-analysis.

PURPOSE: The management of acute stroke is challenging. The aim of this meta-analysis was to determine the efficacy and tolerability of edaravone, with or without thrombolytic therapy, in the treatment of patients with acute ischemic stroke. METHODS: The PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) and cohort studies. Mean differences (MD), risk ratios (RR), 95% confidence interval (CI), and heterogeneity were calculated. FINDINGS: Totals of nine RCTs and four cohort studies were included, for a total of 2102 patients. In patients with acute ischemic stroke, edaravone monotherapy was associated with significantly improved Barthel Index of functioning in activities for daily living (MD, 23.95; 95% CI, 18.48 to 29.41; P < 0.001) and neurologic deficit, (as measured using the National Institutes of Health Stroke Scale score) (MD = -3.49; 95% CI, -5.76 to 1.22; P = 0.003), on short-term follow-up. However, edaravone was not associated with an improved rate of death or disability (RR = 0.75; 95% CI, 0.45 to 1.23; P = 0.25) on long-term follow-up.When plus to thrombolytic therapy, edaravone was associated with significant improvements in recanalization rate (RR = 1.71; 95% CI, 1.05 to 2.77; P = 0.03) and neurologic deficit (MD = 3.97; 95% CI, 5.14 to 2.79; P < 0.001), without an increase in the prevalence of bleeding events (RR = 1.11; 95% CI, 0.76 to 1.62; P = 0.59). However, edaravone did not have a significant effect on death or disability (RR = 0.85; 95% CI, 0.69 to 1.04; P = 0.12). IMPLICATIONS: Based on the findings from the present meta-analysis, edaravone was an effective and well-tolerated neuroprotective agent in these patients with ischemic stroke. With the use of edaravone, activities of daily living and neurologic deficits, along with recanalization rates, were improved on short-term follow-up, but the long-term effects still need confirmation in larger-scale clinical trials.

Effectiveness of Various Dosages and Administration Methods of Tanezumab for the Treatment of Pain in Knee and Hip Osteoarthritis: a Network Meta-Analysis.

BACKGROUND: Previous meta-analyses have reported the superiority of tanezumab versus placebo in the treatment of osteoarthritis (OA). However, they did not compare different injection methods (intravenous or subcutaneous), doses of injection. OBJECTIVE: The goal of this network meta-analysis (NMA) was to evaluate the therapeutic effects of different dosages and methods of injection of tanezumab on relieving pain in patients with OA. METHODS: An online systematic search was performed by using the PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov databases from inception to November 9, 2019. The goal was to identify randomized controlled trials (RCTs) that concentrated on the therapeutic effects of different dosages and methods of injection of tanezumab in patients with OA. The pairwise meta-analyses with the fixed effects model were undertaken with the "meta" package using R 3.6.0 programming language. In addition, an NMA with fixed effects was assessed using a gemtc software. The surface under the cumulative ranking curve value of each intervention was calculated to obtain a hierarchy of treatments. RESULTS: Of the 328 RCTs identified through the literature search, 12 RCTs were included in the current NMA. In terms of the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, the most effective treatment was intravenous injection of tanezumab (10 mg; surface under the cumulative ranking curve values of 90% and 88%, respectively), and the least effective therapy was subcutaneous injection of tanezumab (2.5 mg; 20% and 19%). CONCLUSIONS: To achieve high therapeutic efficacy and avoid treatment failure, an intravenous injection of tanezumab (10 mg) is recommended as an efficacious therapy, facilitating pain relief in patients with OA. However, this conclusion may also be affected by the limitations of this study owing to the small sample size and data heterogeneity, and further research should therefore be conducted to eliminate these limitations and to confirm the findings.

Efficacy and Safety of Polyphenols for Osteoarthritis Treatment: A Meta-Analysis.

PURPOSE: Osteoarthritis (OA) is a chronic and degenerative disorder associated with joint pain and loss of joint function. It is reported that polyphenols could yield articular benefits in patients with OA through the inhabitation of key inflammatory pathways. This meta-analysis was conducted to assess the efficacy and safety of polyphenol products for OA treatment. METHODS: This study included searches of PubMed, EMBASE, and the Cochrane Library databases from inception to November 6, 2019. Randomized controlled trials (RCTs) comparing polyphenols versus NSAIDs or placebo for human OA were included. Standardized mean differences (SMD) or risk ratios (RRs) were calculated for all relevant outcomes. Meta-analyses were conducted by using random effect models, and heterogeneity was assessed by using the I2 statistic. FINDINGS: A total of 18 RCTs (N = 1724) were eligible for analysis. Polyphenol products showed a significant advantage over placebo on pain relief (SMD, -1.11; 95% CI, -1.35 to -0.87) and functional improvement (SMD, -1.14; 95% CI, -1.38 to -0.90). No differences in safety outcomes were detected between polyphenols and placebo. There were no differences in efficacy outcomes between polyphenols and NSAIDs, although patients receiving polyphenols had a lower but nonsignificant risk of experiencing gastrointestinal dysfunction compared with those treated with NSAIDs. Polyphenols and NSAIDs in combination yielded more significant benefits in efficacy than NSAIDs alone. IMPLICATIONS: The results of our study suggest that polyphenols may be a promising alternative for OA by relieving symptoms while reducing safety risks. However, the generalizability of our results may be limited by the quality and sample size of the available research, as well as the heterogeneity between RCTs. High-quality clinical trials are needed to make meaningful clinical practice recommendations.

Effectiveness of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Clinical Trials.

BACKGROUND: The effectiveness of platelet-rich plasma (PRP) injections for knee osteoarthritis and the effects of leukocyte-poor PRP (LP-PRP) versus leukocyte-rich PRP (LR-PRP) are still controversial. PURPOSE: To assess the effectiveness of different PRP injections through a direct and indirect meta-analysis of randomized controlled trials. STUDY DESIGN: Systematic review; Level of evidence, 1. METHODS: A systematic literature search of electronic databases (PubMed, Cochrane Library, and EMBASE) was performed to locate randomized controlled trials published through March 2019 that compared PRP with control treatment. A random-effects meta-analysis was conducted to synthesize the evidence, and meta-regression analyses were conducted to determine the influence of trial characteristics. An indirect comparison was performed to assess the effects of LP-PRP and LR-PRP compared with hyaluronic acid (HA). RESULTS: A total of 21 trials were included. A clinically important benefit for pain relief was seen for intra-articular PRP compared with intra-articular saline (standardized mean difference [SMD] = -1.38 [95% CI, -2.07 to -0.70]; P < .0001; I 2 = 37%) and corticosteroid solution injection (SMD = -2.47 [95% CI, -3.34 to -1.61]; P < .00001; I 2 = 47%). As a result of heterogeneity (I 2 = 89%), there was no conclusive effect compared with HA, even though the pooling effect provided clinically relevant pain relief (SMD = -0.59 [95% CI, -0.97 to -0.21]; P = .003). Indirect meta-analysis showed that there was no significant difference between LR-PRP and LP-PRP. CONCLUSION: PRP injections are beneficial for pain relief and functional improvement in knee osteoarthritis. Larger, randomized high-quality studies are needed to compare the effects of LP-PRP and LR-PRP.

The influence of sample size and gender composition on the meta-analysis conclusion of platelet-rich plasma treatment for osteoarthritis.

OBJECTIVE: The magnitude of the therapeutic effects of intra-articular injection of platelet-rich plasma (PRP) on osteoarthritis (OA) is still under debate. The goal of this study that was a systematic review of randomised controlled trials â€‹of PRP injections for the treatment of OA was to elucidate the therapeutic efficacy of PRP. METHODS: Electronic databases of PubMed, CENTRAL, EMBASE, EBSCO, ClinicalTrials.gov, and International Clinical Trials Registry Platform â€‹were searched from inception to June 2018 for RCTs that compared PRP injections to controls in patients with OA. A random-effects approach was used to compile data and subgroups according to trial size (large trials versus small trials), patient profile (age and gender), and PRP preparation method was performed. RESULTS: Thirty trials met the inclusion criteria and were analysed. All results had unexplained statistical heterogeneity. Patients treated with PRP compared with control showed statistically relevant pain relief and function improvement at short term (standardised mean difference [SMD] â€‹= â€‹-0.62, 95% confidence interval [CI]: -0.98 to -0.27, P â€‹= â€‹0.0006, SMD â€‹= â€‹-0.74, 95% CI: -1.11 to 0.36, P â€‹= â€‹0.0001, respectively), medium term (SMD â€‹= â€‹-0.53, 95% CI: -0.83 to -0.23, P â€‹= â€‹0.0006, SMD â€‹= â€‹-0.50, 95% CI: -0.75 to -0.25, P â€‹= â€‹0.0006), and long term (SMD â€‹= â€‹-0.69, 95% CI: -1.08 to -0.30, P â€‹= â€‹0.0006, SMD â€‹= â€‹-0.68, 95% CI: -0.1.09 to -0.27, P â€‹= â€‹0.001, respectively). A subgroup analysis of the data from large trials and from trials composed of less than 50% female patients revealed that therapeutic effects of the treatment are insignificant. CONCLUSIONS: According to the currently available data, PRP injections are beneficial for pain relief and function improvement in patients with OA. This meta-analysis, however, demonstrated that the efficacy of PRP is related to sample size and gender composition. Thus, more randomised controlled trials of high quality and larger patient size, also including gender aspects, are required to understand this phenomenon. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The translation potential of this meta-analysis is that provided another perspective to analyse the treatment effect of PRP for OA. In future research, phenotypes subpopulation and gender difference of OA patient should be considered for PRP treatment.

Cardiac complications in systemic sclerosis: early diagnosis and treatment.

OBJECTIVE: Systemic sclerosis (SSc) is a remarkably systemic heterogeneous connective tissue disease with many organs involved. The heart is one of the major organs involved, carrying the threat of sudden cardiac death, especially in diffuse cutaneous SSc. This review summarizes the pathophysiology, types, new diagnostic approaches, and imaging and novel therapies of primary cardiac complications while underlining the effects of recently developed non-contrast cardiovascular magnetic resonance (CMR) in early diagnosis. DATA SOURCES: Medline and Embase were searched for articles published up to July 2019. A combination of Medical Subject Headings (MeSH) terms and keywords pertaining to SSc ("Scleroderma, Systemic" OR "Systemic sclerosis" OR' SSc"), AND cardiology ("cardiology" OR "heart" OR "cardiac") were applied to the search strategies. STUDY SELECTION: Literature was mainly printed in English and Chinese about cardiac complications in systemic sclerosis. After selected simply on the title and abstract, the articles were included for the full text. Article type was not limited. RESULTS: Relevant cardiac manifestations are complex, including arrhythmias, pericardial effusion, myocardial dysfunction, and valvular diseases. Even though the symptoms of cardiac complications are well known, unfortunately, they appear to be poor prognostic factors. As systemic sclerosis with cardiac complications has a high mortality rate and patients might have a poor quality of life, it is essential to promote early diagnosis and treatment. With the advent of non-invasive imaging techniques, such as CMR, early diagnosis of cardiac complications in SSc is becoming more effective. CONCLUSIONS: Cardiac complications play an essential role in SSc and carry the threat of sudden cardiac death. More basic and clinical studies are warranted to develop better management of cardiac involvement in patients with SSc.