scholarly journals Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Hu ◽  
Zhi-Yong Xu ◽  
Qian Zhu ◽  
Xi Liu ◽  
Si-Cong Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Advanced Lung Cancer ◽  
Tumor Type ◽  
Significant Difference

BackgroundBrain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer.MethodsElectronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models.ResultsFourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52–0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71–0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56–0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78–1.18; P = 0.72) and 0.97 (95% CI, 0.79–1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings.ConclusionWe demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).

scholarly journals The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204209862110425
Author(s):  
Chenchula Santenna ◽  
Kota Vidyasagar ◽  
Krishna Chaitanya Amarneni ◽  
Sai Nikhila Ghanta ◽  
Balakrishnan Sadasivam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Mortality Reduction ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Grade 3

Introduction: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. Methods: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. Results: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) ( n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%]. Discussion & Conclusion: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. Plain Language Summary Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo. The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir. There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir. There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

scholarly journals Effectiveness of Ivermectin/Doxycycline combination in COVID-19: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Mohammad Ali Omrani ◽  
Amin Salehi-Abargouei ◽  
Behrooz Heydari ◽  
Nazgol Kermanshahi ◽  
Fatemeh Joukar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Hospital Stay ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Viral Clearance ◽  
Control Group ◽  
Clinical Recovery ◽  
Significant Difference ◽  
All Cause Mortality

Abstract BackgroundThis systematic review and meta-analysis aimed to assess the efficacy of the Ivermectin/Doxycycline combination for the treatment of coronavirus disease 2019 (COVID-19).MethodsWe searched PubMed, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar from database inception to August 26, 2021 for relevant studies. We included studies reporting at least one of the outcomes of interest: all-cause mortality; time to clinical recovery; hospital stay and viral clearance. The logarithm of risk ratios or mean differences and their corresponding standard errors for each outcome were pooled using a random-effects model. The risk of bias was assessed using the Cochrane Collaboration's tool for randomized clinical trials and the Newcastle-Ottawa Scale for cohort studies.ResultsFour randomized clinical trials and one prospective study involving 789 patients, including 399 in the Ivermectin/Doxycycline group and 390 in the control group, were enrolled. The all-cause mortality rate of patients with COVID-19 in the Ivermectin/Doxycycline group was 0.79% (2/253), which was lower than in the control group (3.6%; 9/250). However, the difference was not statistically significant (Log risk ratio=-1.288; 95% CI:-2.671, 0.096; P = 0.068; I2 = 0%). The effect of Ivermectin/Doxycycline on time to clinical recovery was found to be significant (Difference in means =-2.427 days; 95% CI:-4.033, -0.820; P = 0.003, I2 = 91.475%). There is no significant effect of Ivermectin/Doxycycline on hospital stay (Difference in means =-0.379 days; 95% CI:-1.965, 1.208; P = 0.640, I2 = 91.95%) and time to negative PCR or viral clearance (Difference in means =-0.768 days; 95% CI:-1.550, 0.013; P = 0.054, I2 = 91.48%).DiscussionBased on low-quality evidence, this meta-analysis showed that Ivermectin/Doxycycline combination is accompanied with shorter time of clinical recovery in COVID-19 patients. However, it did not reduce all-cause mortality, viral clearance, and hospital stay significantly. Not only the number of the studies are limited but also they ranked methodologically medium to low with limited participants. To assess the exact effective dose and efficacy of this combination therapy, high-quality and large-scale randomized clinical trials are needed.OtherThis study was registered in Prospero (registration number: CRD42021272400). The authors declare they have no competing financial interests.

scholarly journals Efficacy and Safety of Tocilizumab in Patients with COVID-19 : A Systematic Review and Meta-Analysis.

2020 ◽  
Author(s):  
Zhenlu Li ◽  
Qianqiu Che ◽  
Mao Li ◽  
Jianping Liu ◽  
Rao Du ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Mortality Rate ◽  
Disease Severity ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Case Control Studies ◽  
Significant Difference ◽  
Critical Patients

Abstract Background Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used to treat patients with 2019 coronavirus disease (COVID-19). Numerous retrospective studies have shown beneficial treatment efficacy. Several recent randomized clinical trials have questioned the efficacy of TCZ in patients with COVID-19. Therefore, we performed an updated systematic review and meta-analysis to explore the effectiveness and safety of tocilizumab recently used for treating patients with COVID-19. Methods Randomized clinical trials (RCTs) and comparative studies that compared the outcomes between TCZ and standard of care (SOC) were analysed. PubMed, EMBASE, and the Cochrane Library (inception to November 20, 2020) were systematically searched. Primary outcomes included mortality and the rate of requirement for mechanical ventilation (MV). In addition, several subgroup analyses stratified by disease severity, publication type and TCZ administration were performed. Results Three RCTs, twenty-one cohort studies and nine case-control studies including 11,206 patients were finally included. The TCZ group included 2,794 patients (24.93%) and the SOC group included 8,412 patients (75.07%). The mortality rate (>14 days) of the TCZ group, 29.63% (590/1,991), was lower than the SOC group, 41.51% (2,380/5,734) (OR 0.64, 0.57 to 0.73; p <0.00001). However, no significant difference in-14-day mortality rates was observed between the two groups (13.53% vs 22.92%, p = 0.21). Meanwhile, the rate of MV was significantly decreased in the TCZ group compared with the SOC group (OR 0.42, 0.22 to 0.83; p = 0.01). According to the results of the subgroup analysis stratified by disease severity, TCZ only reduced the mortality rate for critical patients with COVID-19 compared with SOC (OR 0.60, 0.52 to 0.71; P < 0.00001), particularly for patients in the intensive care unit (ICU) or patients requiring MV. No statistically significant increase was recognized in the rates of secondary infections or thrombosis between the two groups. Conclusions This systematic review and meta-analysis found that the addition of tocilizumab to the SOC might reduce mortality after 14 days in patients with COVID-19, particularly critical patients requiring MV. More extensive RCTs with longer follow-up periods are needed to validate these findings.

scholarly journals Ranking videolaryngoscopes and direct laryngoscopes by orotracheal intubation performance in children: protocol of a systematic review and network meta-analysis of randomized clinical trials at patient level

2021 ◽  
Author(s):  
Clístenes C Carvalho ◽  
Stéphanie LPA Regueira ◽  
Ana Beatriz S Souza ◽  
Lucas MLF Medeiros ◽  
Marielle BS Manoel
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
A Priori ◽  
Orotracheal Intubation ◽  
Sensitivity Analyses ◽  
Intubation Attempt ◽  
Cochrane Central Register ◽  
Meta Regression

ABSTRACTBackgroundVideolaryngoscopy was shown to improve glottic visualization in children as compared to direct laryngoscopy, but at the expenses of delayed time for intubation. As little evidence is available regarding the relative performance of different laryngoscopes at present, we designed this systematic review and network meta-analysis to rank the different videolaryngoscopes (VLs) and direct laryngoscopes (DLs) for orotracheal intubation in children.MethodsWe will conduct a search in PubMed, LILACS, Scielo, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 1) on 27/01/2021. We will include randomized clinical trials fully reported with patients aged ≤ 18 years, making comparisons between different types of laryngoscopes (any of both VLs and DLs) for failed first intubation attempt, intubation time, number of attempts at intubation or number of unsuccessful intubations, failed intubation, glottic view score, or adverse responses to endotracheal intubation. Pooled effects will be estimated by both fixed and random-effects models and presented according to qualitative and quantitative heterogeneity assessment. Sensitivity analyses will be performed as well as a priori subgroup, meta-regression and multiple meta-regression analyses. Additionally, network meta-analyses will be applied to rank the different VLs and DLs. We will also assess the risk of selective publication by funnel plot asymmetry.DiscussionThis systematic review and network meta-analysis aim to understand which laryngoscopes perform better than others for orotracheal intubation.Systematic review registrationThe current protocol was submitted to PROSPERO on 25/01/2021.

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