scholarly journals Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis

2021 ◽  
Author(s):  
Jiawen Deng ◽  
Fangwen Zhou ◽  
Kiyan Heybati ◽  
Saif Ali ◽  
Qi Kang Zuo ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Body Temperature ◽  
Adverse Events ◽  
Observational Studies ◽  
Meta Analysis ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Mortality Incidence ◽  
Mechanical Ventilation Time ◽  
Negative Conversion

Aims: To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and incidence of QT prolongations. Results: Fifty-one studies (n = 61,221) were included. Hydroxychloroquine/chloroquine showed no efficacy in all primary efficacy outcomes, but was associated with increased odds of QT prolongations. Conclusion: Due to a lack of efficacy and increased odds of cardiac adverse events, hydroxychloroquine/chloroquine should not be used for treating hospitalized COVID-19 patients.

scholarly journals Hydroxychloroquine in COVID-19: an updated systematic review and meta-analysis

2020 ◽  
Author(s):  
Jose Chacko ◽  
Gagan Brar ◽  
Robert Premkumar
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Observational Studies ◽  
Meta Analysis ◽  
Chest Ct ◽  
Control Group ◽  
Controlled Trials ◽  
Rt Pcr ◽  
Randomized Controlled ◽  
Negative Conversion

Abstract Background Hydroxychloroquine is being administered among patients with COVID 19 infection in many healthcare systems across the world, considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until August 1, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was administered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included 23 studies, including seven randomized controlled trials and 16 observational studies. Among these, 11,029 patients received hydroxychloroquine alone or in combination, while 12063 did not. Mortality was reported at different points in time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 0.94, 95% CI: 0.72 to 1.22; p = 0.63). Clinical worsening did not differ between patients who received hydroxychloroquine compared to those who did not (OR 0.93, 95% CI: 0.57 to 1.52; p = 0.77). Negative conversion, assessed by RT PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 0.67, CI: 0.21 to 2.11; p = 0.49). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.55; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 5.95, CI: 2.56 to 13.83; p < 0.00001). Conclusions Our meta analysis does not suggest improvement in mortality, clinical progression, or negative conversion by RT PCR among patients with COVID-19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use. Keywords COVID 19, SARS COV 2, hydroxychloroquine, meta analysis

Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans

2020 ◽  
Vol 21 (5) ◽  
pp. 390-399
Author(s):  
Suhaila Omar Alhaj-Suliman ◽  
Gary Milavetz ◽  
Aliasger Karimjee Salem
Keyword(s):  
Adverse Events ◽  
Time Course ◽  
Meta Analysis ◽  
New Drugs ◽  
Maximum Effect ◽  
Primary Efficacy ◽  
Primary Efficacy Endpoint ◽  
Efficacy And Safety ◽  
Model Based ◽  
Osteoarthritic Pain

Background: Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA). Methods: To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach. Results: The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses. Conclusions: This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.

scholarly journals Efficacy and safety of antiplatelet agents in patients with COVID-19 a systematic review and meta-analysis of observational studies

2021 ◽  
Author(s):  
Yan Hu ◽  
Baohui Song
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Risk Of Bias ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
The Relationship

Abstract Coagulopathy and thrombotic events have been reported in patients with coronavirus disease 2019 (COVID-19) frequently. However, the use of antiplatelet agents in COVID-19 is yet to be investigated. This article systematically reviewed the relationship between use of antiplatelet agents and major outcomes of COVID-19 patients. In total, 12 studies met our eligibility criteria. Due to high heterogeneity, we excluded three studies with high risk of bias. The result showed that antiplatelet therapy did not related to a higher mortality of COVID-19 patients (OR=1.01, 95% CI=0.77-1.33, I2=0%, P=0.88). However, the use of antiplatelet agents was associated with a lower risk of ICU admission (OR=0.63, 95% CI= 0.40-0.98, I2=0%, P=0.68) and mechanical ventilation (OR=0.57, 95% CI= 0.38-0.85, I2=0%, P=0.75) compared with those without antiplatelets. In conclusion, current results did not support that antiplatelets will cause greater mortality in patients with COVID-19 infection. Antiplatelet agents should be continued in COVID-19 patients, unless clinically indicated.

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Specific Immunotherapy ◽  
Meta Analysis ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

scholarly journals Comparative efficacy and safety of different regimens of ranibizumab for neovascular age-related macular degeneration: a network meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040906
Author(s):  
Xinyu Zhao ◽  
Lihui Meng ◽  
Youxin Chen
Keyword(s):  
Adverse Events ◽  
Macular Degeneration ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Age Related ◽  
Randomised Controlled

ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=−0.94, 95% CI −2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

2021 ◽  
pp. 10.1212/CPJ.0000000000001143
Author(s):  
Glenardi Glenardi ◽  
Tutwuri Handayani ◽  
Jimmy Barus ◽  
Ghea Mangkuliguna
Keyword(s):  
Systematic Review ◽  
Placebo Group ◽  
Adverse Events ◽  
Respiratory Symptoms ◽  
Meta Analysis ◽  
Motor Fluctuation ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Improve Motor Function

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.

scholarly journals Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e047344
Author(s):  
Qingwu Wu ◽  
Lianxiong Yuan ◽  
Huijun Qiu ◽  
Xinyue Wang ◽  
Xuekun Huang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Chronic Rhinosinusitis ◽  
Randomised Controlled Trials ◽  
Nasal Polyps ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomised Controlled

ObjectivesTo assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.DesignSystematic review and meta-analysis.Data sourcesA comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020.Eligibility criteriaRandomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP.Data extraction and synthesisTwo independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic.ResultsA total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=−1.20; 95% CI −1.48 to −0.92), Nasal Congestion Score (MD=−0.67; 95% CI −0.86 to −0.48), Sino-Nasal Outcome Test-22 (MD=−15.62; 95% CI −19.79 to −11.45), Total Nasal Symptom Score (MD=−1.84; 95% CI −2.43 to −1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61).ConclusionsThis was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated.PROSPERO registration numberCRD42020207639.

scholarly journals Efficacy and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis patients: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e050004
Author(s):  
Wenjuan Wu ◽  
Lingxiao Qiu ◽  
Jizhen Wu ◽  
Xueya Liu ◽  
Guojun Zhang
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Acute Exacerbation ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomised Controlled

ObjectivesIdiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a common histological pattern of interstitial pneumonia. To analyse the efficacy and safety of pirfenidone in the treatment of IPF, a systematic review and meta-analysis was performed.DesignThis is a meta-analysis study.ParticipantsPatients were diagnosed as IPF.InterventionsUse of pirfenidone.Primary and secondary outcomeProgression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.MeasuresThe inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.ResultsA total of 9 randomised controlled trials with 1011 participants receiving pirfenidone and 912 controls receiving placebo were summarised. The pooled result suggested a statistically significant difference inall-cause mortality after pirfenidone use, with a summarised relative ratio of 0.51 (p<0.01). Longer PFS was observed in patients receiving pirfenidone compared with those who were given placebo (p<0.01). The IPF groups presented a high incidence of adverse events with a pooled relative ratio of 3.89 (p<0.01).ConclusionsPirfenidone can provide survival benefit for patients with IPF. Pirfenidone treatment was also associated with a longer PFS, a lower incidence of acute exacerbation and worsening of IPF.

scholarly journals Efficacy and safety of repetitive transcranial magnetic stimulation for generalised anxiety disorder: A meta-analysis

2019 ◽  
Vol 32 (5) ◽  
pp. e100051
Author(s):  
Huiru Cui ◽  
Lijuan Jiang ◽  
Yanyan Wei ◽  
Wei Li ◽  
Hui Li ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Anxiety Disorder ◽  
Adverse Events ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Efficacy And Safety ◽  
Generalised Anxiety Disorder ◽  
Grade Approach

BackgroundPharmacological and conventional non-pharmacological treatments are only moderately effective in treating generalised anxiety disorder (GAD). Recently, repetitive transcranial magnetic stimulation (rTMS) has attracted interest because of its potential therapeutic value.AimTo investigate the efficacy and safety of rTMS treatment for GAD.MethodsLiterature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018. The included studies’ bias risk was assessed using Cochrane risk of bias assessment tool. Meta-analysis was performed to compute the standardised mean difference (SMD) and risk ratio (RR) along with its 95% CIs through using RevMan V.5.3. Heterogeneity was inspected by I2 and the χ2 test. We performed subgroup analysis and meta-regression to investigate heterogeneity. We used funnel plot to assess publication bias. We used the GRADE approach to assess the whole quality of evidence.ResultsTwenty-one studies, with a total sample size of 1481, were analysed. The risk of bias in most studies included is moderate, the majority of which are lacking of blinding methods of treatment allocation. The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score (SMD=−0.68; 95% CI −0.89 to −0.46). None of the 21 studies included here reported severe adverse events. As for dropout rates, there are no statistically significant differences between the two groups (RR 1.14, 95% CI 0.72 to 1.82) or adverse events (RR 0.95, 95% CI 0.77 to 1.18). No particular influence on the heterogeneity of any variable was observed. The risk of publication bias was low. According to the GRADE approach, the evidence levels of primary outcome (treatment effects) and secondary outcomes (acceptability and safety) were rated as ‘medium’.ConclusionThe use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD. However, we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis. Future high-quality clinical trials are needed to confirm our results.

scholarly journals Targeted therapies for previously treated advanced or metastatic renal cell carcinoma: systematic review and network meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e024691 ◽  
Author(s):  
Charlotta Karner ◽  
Kayleigh Kew ◽  
Victoria Wakefield ◽  
Natalie Masento ◽  
Steven J Edwards
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Sensitivity Analysis ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Observational Studies ◽  
Meta Analysis ◽  
Targeted Treatment

ObjectiveTo compare the effectiveness and safety of treatments for advanced or metastatic renal cell carcinoma (amRCC) after treatment with vascular endothelial growth factor (VEGF)-targeted treatment.DesignSystematic review and network meta-analysis of randomised controlled trials (RCTs) and comparative observational studies. MEDLINE, EMBASE and Cochrane Library were searched up to January 2018.ParticipantsPeople with amRCC requiring treatment after VEGF-targeted treatment.InterventionsAxitinib, cabozantinib, everolimus, lenvatinib with everolimus, nivolumab, sorafenib and best supportive care (BSC).OutcomesPrimary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were objective response rate (ORR), adverse events, and health-related quality of life (HRQoL).ResultsTwelve studies were included (n=5144): five RCTs and seven observational studies. Lenvatinib with everolimus significantly increased OS and PFS over everolimus (HR 0.61, 95% Credible Interval [95%CrI]: 0.36 to 0.96 and 0.47, 95%CrI: 0.26 to 0.77, respectively) as did cabozantinib (HR 0.66, 95%CrI: 0.53 to 0.82 and 0.51, 95%CrI: 0.41 to 0.63, respectively). This remained the case when observational evidence was included. Nivolumab also significantly improved OS versus everolimus (HR 0.74, 95%CrI: 0.57 to 0.93). OS sensitivity analysis, including observational studies, indicates everolimus being more effective than axitinib and sorafenib. However, inconsistency was identified in the OS sensitivity analysis. PFS sensitivity analysis suggests axitinib is more effective than everolimus, which may be more effective than sorafenib. The results for ORR supported the OS and PFS analyses. Nivolumab is associated with fewer grade 3 or grade 4 adverse events than lenvatinib with everolimus or cabozantinib. HRQoL could not be analysed due to differences in tools used.ConclusionsLenvatinib with everolimus, cabozantinib and nivolumab are effective in prolonging the survival for people with amRCC subsequent to VEGF-targeted treatment, but there is considerable uncertainty about how they compare to each other and how much better they are than axitinib and sorafenib.PROSPERO registrationnumberCRD42017071540.

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