scholarly journals Comparative evaluation of cardiovascular risks among nine FDA-approved VEGFR-TKIs in patients with solid tumors: a Bayesian network analysis of randomized controlled trials

2021 ◽  
Author(s):  
Wanting Hou ◽  
Mingfu Ding ◽  
Xiaohua Li ◽  
Xiaohan Zhou ◽  
Qing Zhu ◽  
...  
Keyword(s):  
Bayesian Network ◽  
Randomized Controlled Trials ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Splitting Method ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Increased Risk

Abstract Purpose The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors. Methods Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for the randomized controlled trials. We have included 45 randomized controlled trials (RCTs) associated with nine VEGFR-TKIs Food and Drug Administration (FDA)-approved drugs used to treat patients with solid tumors. To evaluate the trials’ risk of bias, Cochrane Risk of Bias Tool was assessed. A direct comparison was assessed by RevMan5.3 software, calculating the odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was tested by the I2 statistic and Chi-square test for P value. Bayesian network meta-analysis was performed using Stata 15.0 and GeMTC 0.14.3 software, calculated OR along with corresponding 95% credible interval (CrI). The model’s convergence was evaluated by the potential scale reduced factor (PSRF). Consistency between direct and indirect comparisons was assessed by the “node-splitting” method. Results In this network meta-analysis, a total of 20,027 patients from 45 randomized controlled trials and associated with nine FDA-approved VEGFR-TKIs (axitinib, cabozantinib, lenvatinib, nintedanib, pazopanib, regorafenib, sorafenib, sunitinib, vandetanib), were enrolled. Findings indicated that lenvatinib had the most significant probability of provoking all grades cardiovascular incident and hypertension, followed by vandetanib, cabozantinib, axitinib, pazopanib, sorafenib, sunitinib, regorafenib and nintedanib. The nine agent’s severe cardiovascular and severe hypertension risk was probably similar. The ranking probability of cardiac toxicity shows that vandetanib ranked most likely to have the highest risk for cardiotoxicity among all the VEGFR-TKIs reviewed, followed by pazopanib, axitinib, sorafenib, sunitinib. In contrast, regorafenib and nintedanib did not exhibit an increased risk of cardiac damage. Conclusions The association between the nine VEGFR-TKIs with potential cardiotoxicity occurrence was reviewed. Both the regorafenib and nintedanib did not display detectable signs of cardiotoxic damage. In contrast, lenvatinib and vandetanib are ranked to have the most severe cardiotoxicity side impacts. These results may provide information for clinical practice guidelines, implementing strategies in selecting the adequate VEGFR-TKIs, and understanding the cardiovascular toxicity inflicted by the VEGFR-TKIs. PROSPERO identifier CRD 42,020,167,307.

scholarly journals Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials

2020 ◽  
Vol 11 ◽  
Author(s):  
Wenqiang Kong ◽  
Huiyuan Deng ◽  
Jie Wan ◽  
Yilu Zhou ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Anxiety Disorder ◽  
Randomized Controlled Trials ◽  
Remission Rate ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Double Blind ◽  
Randomized Controlled

Background: Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders associated with substantial dysfunction and socioeconomic burden. Pharmacotherapy is the first choice for GAD. Remission [Hamilton Anxiety Scale (HAM-A) score ≤7] is regarded as a crucial treatment goal for patients with GAD. There is no up-to-date evidence to compare remission rate and tolerability of all available drugs by using network meta-analysis. Therefore, the goal of our study is to update evidence and determine the best advantageous drugs for GAD in remission rate and tolerability profiles.Method: We performed a systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs). We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, wanfang data, China Biology Medicine and ClinicalTrials.gov from their inception to March 2020 to identify eligible double-blind, RCTs reporting the outcome of remission in adult patients who received any pharmacological treatment for GAD. Two reviewers independently assessed quality of included studies utilizing the Cochrane Collaboration’s risk of bias tool as described in Cochrane Collaboration Handbook and extracted data from all manuscripts. Our outcomes were remission rate (proportion of participants with a final score of seven or less on HAM-A) and tolerability (treatments discontinuations due to adverse events). We calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) of each outcome via pairwise and network meta-analysis with random effects.Results: Overall, 30 studies were included, comprising 32 double-blind RCTs, involving 13,338 participants diagnosed as GAD by DSM-IV criteria. Twenty-eight trials were rated as moderate risk of bias, four trials as low. For remission rate, agomelatine (OR 2.70, 95% CI 1.74–4.19), duloxetine (OR 1.88, 95% CI 1.47–2.40), escitalopram (OR 2.03, 95% CI 1.48–2.78), paroxetine (OR 1.74, 95% CI 1.25–2.42), quetiapine (OR 1.88, 95% CI 1.39–2.55), and venlafaxine (OR 2.28, 95% CI 1.69–3.07) were superior to placebo. For tolerability, sertraline, agomelatine, vortioxetine, and pregabalin were found to be comparable to placebo. However, the others were worse than placebo in terms of tolerability, with ORs ranging between 1.86 (95% CI 1.25–2.75) for tiagabine and 5.98 (95% CI 2.41–14.87) for lorazepam. In head-to-head comparisons, agomelatine, duloxetine, escitalopram, quetiapine, and venlafaxine were more efficacious than tiagabine in terms of remission rate, ORs from 1.66 (95% CI 1.04–2.65) for duloxetine to 2.38 (95% CI 1.32–4.31) for agomelatine. We also found that agomelatine (OR 2.08, 95% CI 1.15–3.75) and venlafaxine (OR 1.76, 95% CI 1.08–2.86) were superior to vortioxetine. Lorazepam and quetiapine were poorly tolerated when compared with other drugs.Conclusions: Of these interventions, only agomelatine manifested better remission with relatively good tolerability but these results were limited by small sample sizes. Duloxetine, escitalopram, venlafaxine, paroxetine, and quetiapine showed better remission but were poorly tolerated.

scholarly journals Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Man Yang ◽  
Qiangsheng He ◽  
Fang Gao ◽  
Krish Nirantharakumar ◽  
Tonny Veenith ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Risk Score ◽  
Proton Pump ◽  
Stroke Risk ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Increased Risk

Abstract Background Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.

Risk of Venous Thromboembolism in Patients With Cancer Treated With Cisplatin: A Systematic Review and Meta-Analysis

2012 ◽  
Vol 30 (35) ◽  
pp. 4416-4426 ◽  
Author(s):  
Sonia Seng ◽  
Ziyue Liu ◽  
Sophia K. Chiu ◽  
Tracy Proverbs-Singh ◽  
Guru Sonpavde ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Incidence Rates ◽  
Systemic Review ◽  
Controlled Trials ◽  
Advanced Solid Tumors ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Venous Thromboembolic Events

Purpose Several reports suggest that cisplatin is associated with an increased risk of thromboembolism. However, because the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy has not been well described, we conducted a systemic review and meta-analysis of randomized controlled trials evaluating the incidence and risk of VTEs associated with cisplatin-based chemotherapy. Methods PubMed was searched for articles published from January 1, 1990, to December 31, 2010. Eligible studies included prospective randomized phase II and III trials evaluating cisplatin-based versus non–cisplatin-based chemotherapy in patients with solid tumors. Data on all-grade VTEs were extracted. Study quality was calculated using Jadad scores. Incidence rates, relative risks (RRs), and 95% CIs were calculated using a random effects model. Results A total of 8,216 patients with various advanced solid tumors from 38 randomized controlled trials were included. The incidence of VTEs was 1.92% (95% CI, 1.07 to 2.76) in patients treated with cisplatin-based chemotherapy and 0.79% (95% CI, 0.45 to 1.13) in patients treated with non–cisplatin-based regimens. Patients receiving cisplatin-based chemotherapy had a significantly increased risk of VTEs (RR, 1.67; 95% CI, 1.25 to 2.23; P = .01). Exploratory subgroup analysis revealed the highest RR of VTEs in patients receiving a weekly equivalent cisplatin dose > 30 mg/m2 (2.71; 95% CI, 1.17 to 6.30; P = .02) and in trials reported during 2000 to 2010 (1.72; 95% CI, 1.27 to 2.34; P = .01). Conclusion Cisplatin is associated with a significant increase in the risk of VTEs in patients with advanced solid tumors when compared with non–cisplatin-based chemotherapy.

scholarly journals Convalescent plasma therapy for COVID-19 patients: a protocol of a prospective meta-analysis of randomized controlled trials

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lajos Szakó ◽  
Nelli Farkas ◽  
Szabolcs Kiss ◽  
Szilárd Váncsa ◽  
Noémi Zádori ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Randomized Controlled Trials ◽  
Organ Failure ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Plasma Therapy ◽  
Monthly Basis ◽  
Randomized Controlled

Abstract Background Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events. Methods A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries. A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator. An update of the search of the registries and the first search of the databases will be done on the 21st of July. Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes (mortality and organ failure), we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables (treatment Y/N, outcome Y/N). Data from models with multivariate adjustment (hazard ratios, odds ratio, risk ratio) will be preferred for the analysis. P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population. Discussion Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis.

scholarly journals Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2984
Author(s):  
Stepan M. Esagian ◽  
Christos D. Kakos ◽  
Emmanouil Giorgakis ◽  
Lyle Burdine ◽  
J. Camilo Barreto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Transarterial Chemoembolization ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Curative Intent ◽  
Randomized Controlled

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

scholarly journals Effects of Supervised Multimodal Exercise Interventions on Cancer-Related Fatigue: Systematic Review and Meta-Analysis of Randomized Controlled Trials

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
José Francisco Meneses-Echávez ◽  
Emilio González-Jiménez ◽  
Robinson Ramírez-Vélez
Keyword(s):  
Systematic Review ◽  
Resistance Training ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Exercise Interventions ◽  
Training Interventions ◽  
Randomized Controlled ◽  
Cancer Related Fatigue

Objective. Cancer-related fatigue (CRF) is the most common and devastating problem in cancer patients even after successful treatment. This study aimed to determine the effects of supervised multimodal exercise interventions on cancer-related fatigue through a systematic review and meta-analysis.Design. A systematic review was conducted to determine the effectiveness of multimodal exercise interventions on CRF. Databases of PubMed, CENTRAL, EMBASE, and OVID were searched between January and March 2014 to retrieve randomized controlled trials. Risk of bias was evaluated using the PEDro scale.Results. Nine studiesn=772were included in both systematic review and meta-analysis. Multimodal interventions including aerobic exercise, resistance training, and stretching improved CRF symptoms (SMD=-0.23; 95% CI: −0.37 to −0.09;P=0.001). These effects were also significant in patients undergoing chemotherapyP<0.0001. Nonsignificant differences were found for resistance training interventionsP=0.30. Slight evidence of publication bias was observedP=0.04. The studies had a low risk of bias (PEDro scale mean score of 6.4 (standard deviation (SD) ± 1.0)).Conclusion. Supervised multimodal exercise interventions including aerobic, resistance, and stretching exercises are effective in controlling CRF. These findings suggest that these exercise protocols should be included as a crucial part of the rehabilitation programs for cancer survivors and patients during anticancer treatments.

scholarly journals Therapies for Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2017 ◽  
Vol 11 (1) ◽  
pp. 346-354 ◽  
Author(s):  
Kannan Sridharan ◽  
Gowri Sivaramakrishnan
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Meibomian Gland ◽  
Risk Of Bias ◽  
Present Review ◽  
Meibomian Gland Dysfunction ◽  
Controlled Trials ◽  
Schirmer’S Test ◽  
Randomized Controlled

Introduction: Meibomian Gland Dysfunction (MGD) is a common, often overlooked, chronic condition affecting eyes for which various therapies are being evaluated. Considering the absence of a systematic review and meta-analysis, the present review was carried out. Methods: An appropriate search strategy eligibility criteria were framed and electronic databases were scrutinized for appropriate literature. Randomized Controlled Trials (RCTs) enrolling patients diagnosed with MGD were included. Outcome measures were Tear Break Up Time (TBUT), Schirmer’s test, Meibomian Gland (MG) secretion score, MG plugging score, OSDI and SPEED. Cochrane’s tool was used to assess the risk of bias and Forest plot were generated either with fixed or random effects model, with Standardized Mean Difference (SMD). Results: TBUTs, Schirmer’s test and OSDI scores for systemic antimicrobials with placebo were 1.58 [1.33, 1.83], 2.93 [0.78, 5.09] and -3.58 [-4.28, -2.89] respectively. No quantitative synthesis was attempted for either mebiomian plugging or meibomian secretion scores and no significant changes were observed with any other outcome parameter. Conclusion: Only the systemic antimicrobials were found to improve the clinical features of meibomian gland dysfunction. Varying effects of different therapeutic agents (heat therapies, omega-3-fatty acids and castor oil) were identified for MGD but the risk of bias pertaining to randomization and allocation concealment was found to be associated with most of the current RCTs. More high quality evidence is required to confirm the findings of the present review.

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