scholarly journals The Effectiveness of Tocilizumab in the Treatment of COVID-19 in Adults: A Meta-Analysis of Randomized Controlled Trials.

Author(s):  
Chun Chen ◽  
ZeMei Zhou ◽  
Jing Zhang

Abstract Background: Since December 2019, COVID-19 has spread to the world which leads to a global health threat. We aimed to investigate the effectiveness of tocilizumab on COVID-19 patients.Methods: We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and WHO international Clinical Trials Registry Platform (ICTRP) from their inception to March 10, 2021 for randomized controlled trials (RCTs) on tocilizumab supplementation in adults with COVID-19 disease. The primary outcomes were mortality at 28-30 day and 60-day, incidence of mechanical ventilation (MV), composite outcome of death or MV, time to hospital discharge, and intensive care unit (ICU) admissions. A random-effects meta-analysis model was used to pool studies. Results: Eleven studies with a total of 6,579 patients were included in our meta-analysis, of which 3,406 and 3,173 were respectively assigned to the tocilizumab and control groups. Tocilizumab could significantly reduce 28-30 day mortality (RR = 0.89, 95% CI 0.80-0.99, P = 0.04), incidence of MV (RR= 0.79, 95% CI 0.71-0.89, P = 0.0001), composition outcome of MV or death (RR = 0.81, 95% CI 0.72-0.90, P = 0.0002), time to hospital discharge (HR = 1.30, 95% CI 1.16-1.45, P < 0.00001 ), ICU admissions (RR = 0.64, 95% CI 0.47-0.88, P = 0.006), serious infection (RR = 0.61, 95% CI 0.40-0.94, P = 0.02) and events of serious adverse advents (RR = 0.64, 95% CI 0.47-0.86, P = 0.004). There was no significant difference between tocilizumab and control groups in 60-day mortality and adverse events (AEs).Conclusions: Tocilizumab could reduce the short-term mortality, incidence of MV, composite outcome of death or MV, ICU admissions, serious infection and events of serious adverse advents, and shorten the time to hospital discharge in hospitalized patients with COVID-19. The optimal effective dose needs to be confirmed by further studies.

2019 ◽  
Vol 8 (11) ◽  
pp. 1884 ◽  
Author(s):  
Chien-Ju Lin ◽  
Yu-Chen Chang ◽  
Yu-Han Chang ◽  
Yu-Hsuan Hsiao ◽  
Hsin-Hui Lin ◽  
...  

Prenatal anxiety is extremely common and may result in adverse effects on both the mother and the baby. Music interventions have been used to reduce anxiety in various medical patients and in pregnant women during childbirth. This study aims to assess the clinical efficacy of music interventions in women during pregnancy rather than during labor. Seven databases were searched from inception to September 2019 without language restrictions. We included only randomized controlled trials that compared music intervention and control groups for anxiety reduction in pregnant women. We used the revised Cochrane risk-of-bias tool (RoB 2.0) for quality assessment. Finally, 11 studies with 1482 participants were included. The pooled meta-analysis results showed that music interventions significantly decreased anxiety levels (standardized mean difference (SMD), −0.42; 95% confidence interval (CI), −0.83 to −0.02; I2 = 91%). Moreover, subgroup analysis showed that listening to music at home had significant anxiolytic benefits (SMD, −0.28; 95% CI, −0.47 to −0.08; I2 = 0%). However, meta-regression revealed a nonsignificant trend for increase in the anxiety-reducing effects of music interventions with increasing maternal age. In conclusion, music interventions may be beneficial in reducing anxiety and may be applied in pregnant women.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lajos Szakó ◽  
Nelli Farkas ◽  
Szabolcs Kiss ◽  
Szilárd Váncsa ◽  
Noémi Zádori ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sha Yang ◽  
Yujia J. Luo ◽  
Cong Luo

Background: There is no uniform treatment for pathological scars, including keloids and hypertrophic scars, in clinic currently. Previously, multiple randomized controlled trials have examined the clinical efficacy of different treatments. Nonetheless, the results are inconsistent, and many treatments have not been directly compared. This makes it difficult to conclude which approach is more favorable, in terms of efficacy and safety, for the treatment of pathological scarring. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid.Methods: Relevant literature from PubMed, Medline, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CCRCT), and WHO International Clinical Trials Registry Platform (WHO-ICTRP) were searched, from database inception through November 2020. Randomized clinical trials evaluating different treatment strategies of pathological scars, including triamcinolone acetonide (TAC), verapamil (VER), 5-fluorouracil (5-FU), botulinum toxin A (BTA), bleomycin (BLM), and silicone gels were included in the study.Results: The network meta-analysis included a total of 2,009 patients from 29 studies. A network meta-analysis of injection and topical treatment strategies showed that the efficacy of TAC combined with BTA was best in the treatment of pathological scars. Combination therapies of TAC with 5-FU and TAC with BTA significantly improved the clinical efficiency. However, there was no statistically significant difference between other treatment strategies. The order of efficacy predicted by the surface under the cumulative ranking (SUCRA) curve was as follows: TAC+BTA (82.2%) > TAC+5-FU (69.8%) > BTA (67.3%) > 5-FU+silicone (59.4%) > TAC+silicone (58.3%) > 5-FU (49.8%) > BLM (42.0%) > TAC (26.7%) > VER (26.2%) > silicone (18.3%). There was no publication bias revealed based on the funnel diagram.Conclusion: This study recommends intralesional injection of TAC-BTA and TAC-5-FU combined therapies. But for patients who cannot tolerate the side effects, the use of silicone gels in combination with TAC is recommended. However, these conclusions need to be further confirmed by more randomized controlled trials.


2020 ◽  
Author(s):  
Mi-Zhou Wang ◽  
Rui Dong ◽  
Li-Na Jia ◽  
Deng-Bin Ai ◽  
Jian-Hua Zhang

Abstract Background: Several studies have investigated the effects of intrathecal magnesium sulfate as an adjuvant for bupivacaine; however, their conclusions are inconsistent. Therefore, it is necessary to conduct a meta-analysis on this topic.Methods We searched Pubmed, EMBASE (OvidSP) and Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) comparing the effect of intrathecal bupivacaine combined with magnesium sulfate versus bupivacaine alone in adults using spinal anesthesia.Results Eighteen studies that met our inclusion criteria were included in our analysis. We found that the addition of intrathecal magnesium sulfate to bupivacaine provided a longer duration of analgesia (SMD 0.99; 95% CI [0.45, 1.52], P = 0.0003, I2 = 93%), prolonged the duration of sensory block (MD=106.69; 95% CI, 60.93-152.45; P<0.00001), delayed the onset of sensory block (SMD 1.20; 95% CI [0.65, 1.75], P =<0.0001, I2 = 91%) and motor block (SMD 1.46; 95% CI [0.23, 2.69], P =0.02, I2 = 96%), decreased the requirement for rescue analgesia (SMD -0.81; 95% CI [-1.06, -0.56], P < 0.00001, I2 = 11%). For duration of motor block, and incidence of postoperative adverse events (such as nausea and vomiting, hypotension, bradycardia, pruritus, shivering and neurological deficit), no statistically differences were observed between the 2 groups.Conclusions Our meta-analysis demonstrated that intrathecal magnesium sulfate combined with bupivacaine prolongs the dusration of analgesia, without an impact on the adverse events. However, the quality of evidence was very low when using GRADE to assess it. Given adverse effects before use, more high-quality trials with large samples are required before magnesium sulfate is routinely used as a intrathecal adjunct.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
James S McKinney ◽  
William J Kostis ◽  
John B Kostis

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.


2020 ◽  
Vol 11 ◽  
Author(s):  
Qingyang Shi ◽  
Lizi Tan ◽  
Zhe Chen ◽  
Long Ge ◽  
Xiaoyan Zhang ◽  
...  

Acne has several effects on physical symptoms, but the main impacts are on the quality of life, which can be improved by treatment. There are several acne treatments but less evidence comparing their relative efficacy. Thus, we assessed the comparative efficacy of pharmacological and nonpharmacological interventions for acne. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2019, to include randomized controlled trials for acne that compared topical antibiotics (TA), benzoyl peroxide (BPO), topical retinoids (TR), oral antibiotics (OA), lasers, light devices including LED device (LED), photodynamic therapy (PDT), and intense pulsed light, chemical peels (CP), miscellaneous therapies or complementary and alternative medicine (MTCAM), or their combinations. We performed Bayesian network meta-analysis with random effects for all treatments compared with placebo and each other. Mean differences (MDs) of lesions count and risk ratios of adverse events with their 95% credible intervals (CrIs) were calculated, and all interventions were ranked by the Surface Under the Cumulative Ranking (SUCRA) values. Additional frequentist additive network meta-analysis was performed to detect the robustness of results and potential interaction effects. Sensitivity analyses were carried out with different priors, and metaregression was to adjust for nine potential effect modifiers. In the result, seventy-three randomized controlled trials (27,745 patients with mild to moderate acne), comparing 30 grouped intervention categories, were included with low to moderate risk of bias. For adverse effects, OA had more risk in combination treatment with others. For noninflammatory lesions reduction, seventeen interventions had significant differences comparing with placebo and three interventions (TR+BPO: MD = −21.89, 95%CrI [−28.97, −14.76]; TR+BPO+MTCAM: −22.48 [−34.13, −10.70]; TA+BPO+CP: −20.63 [−33.97, −7.13]) were superior to others with 94, 94, and 91% SUCRA values, respectively. For inflammatory lesions reduction, nineteen interventions were significantly better than placebo, and three interventions (TR+BPO: MD = −12.13, 95%CrI [−18.41, −5.80]; TR+BPO+MTCAM: −13.21 [−.39, −3.04]; LED: −11.30 [−18.34, −4.42]) were superior to others (SUCRA: 81, 81, and 77%, respectively). In summary of noninflammatory and inflammatory lesions results, TR+BPO and TA+BPO were the best options compared to others. The frequentist model showed similar results as above. In summary, current evidence supports the suggestion that TR+BPO and TA+BPO are the best options for mild to moderate acne. LED is another option for inflammatory lesions when drug resistance occurs. All the combinations involved with OA showed more risk of adverse events than others. However, the evidence of this study should be cautiously used due to the limitations.


Author(s):  
Yuji Kanejima ◽  
Takayuki Shimogai ◽  
Masahiro Kitamura ◽  
Kodai Ishihara ◽  
Kazuhiro P. Izawa

The objective effects of early mobilization on physical function in patients after cardiac surgery remain unknown. The purpose of the present study was to clarify the effects of early mobilization on physical function in patients after cardiac surgery through meta-analysis. Four electronic databases were searched on 2 August 2019. We used search keywords related to “early mobilization”, “cardiac surgery”, and “randomized controlled trials”. All randomized controlled trials conducting early mobilization after cardiac surgery were included. We defined early mobilization as the application of physical activity within the first five postoperative days. Citations and data extraction were independently screened in duplicate by two authors. The meta-analysis was conducted using random-effects modeling with EZR software. The primary outcome was the distance walked during the six-minute walking test at hospital discharge. Six randomized controlled trials comprising 391 patients were included following screening of 591 studies. All studies included coronary artery bypass grafting as the cardiac surgery conducted. Early mobilization started on postoperative days 1–2 and was conducting twice daily. Early mobilization showed a trend of being combined with respiratory exercise or psychoeducation. The meta-analysis showed that the distance walked during the 6-min walking test improved by 54 m (95% confidence interval, 31.1–76.9; I2 = 52%) at hospital discharge. The present study suggested that early mobilization after cardiac surgery may improve physical function at discharge.


2020 ◽  
Vol 109 (11) ◽  
pp. 1381-1391 ◽  
Author(s):  
Hans-Josef Feistritzer ◽  
Alexander Jobs ◽  
Suzanne de Waha-Thiele ◽  
Ingo Eitel ◽  
Anne Freund ◽  
...  

Abstract Aims To perform a pairwise meta-analysis of randomized controlled trials (RCTs) comparing multivessel percutaneous coronary intervention (PCI) and culprit vessel-only PCI in ST-elevation myocardial infarction (STEMI) patients without cardiogenic shock. Methods We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for RCTs comparing multivessel PCI with culprit vessel-only PCI in STEMI patients without cardiogenic shock and multivessel coronary artery disease. Only RCTs reporting mortality or myocardial reinfarction after at least 6 months following randomization were included. Hazard ratios (HRs) were pooled using random-effect models. Results Nine RCTs were included in the final analysis. In total, 523 (8.3%) of 6314 patients suffered the combined primary endpoint of death or non-fatal reinfarction. This primary endpoint was significantly reduced with multivessel PCI compared to culprit vessel-only PCI (HR 0.63, 95% confidence interval [CI] 0.43–0.93; p = 0.03). This finding was driven by a reduction of non-fatal reinfarction (HR 0.64, 95% CI 0.52–0.79; p = 0.001), whereas no significant reduction of all-cause death (HR 0.77, 95% CI 0.44–1.35; p = 0.28) or cardiovascular death (HR 0.64, 95% CI 0.37–1.11; p = 0.09) was observed. Conclusions In STEMI patients without cardiogenic shock multivessel PCI reduced the risk of death or non-fatal reinfarction compared to culprit vessel-only PCI.


2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiuli Li ◽  
Peng Chang ◽  
Qiongying Wang ◽  
Hao Hu ◽  
Feng Bai ◽  
...  

To determine the effects of ACEIs on arterial stiffness, a meta-analysis of randomized controlled trials was conducted. Relevant articles that investigated the effects of ACEIs on arterial stiffness from PubMed, Embase, and the Cochrane library from inception to September 2018 were systematically retrieved. The investigated outcomes included brachial-ankle pulse wave velocity (ba-PWV) and carotid-femoral PWV (cf-PWV) by using weighted mean differences (WMDs) and 95% confidence intervals (CIs) with the random-effects model. A total of 17 RCTs including 1,458 individuals were included. The summary results indicated no significant differences between ACEIs and control for ba-PWV and cf-PWV. Also, no significant differences between ACEI and control for ba-PWV and cf-PWV were observed in hypertensive patients, while the therapeutic effects of ACEI versus placebo showed statistically significant difference. Moreover, subgroup analysis indicated that the levels of ba-PWV were significantly associated if the study was conducted in Western countries, mean age <60.0 years, percentage male ≥60.0%, compared with ARBs, baseline PWV <10.0, and high-quality study. Furthermore, the significant levels of cf-PWV in patients who received ACEIs were observed when percentage male was ≥60.0% and the studies were of high-quality. Finally, no significant differences were observed between ACEIs and other antihypertensive drugs regarding the changes of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The overall analysis suggested no significant differences between ACEIs and other antihypertensive drugs for ba-PWV and cf-PWV levels, whereas ACEIs versus placebo showed lower levels of ba-PWV and cf-PWV.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 236-236
Author(s):  
Helen Mahony ◽  
Ambuj Kumar ◽  
Rahul Mhaskar ◽  
Branko Miladinovic ◽  
Keith Wheatley ◽  
...  

Abstract Abstract 236 Background: There is little consensus on which maintenance therapy clinicians should choose for their patients. Since 1999, the three novel agents of bortezomib, lenalidomide, and thalidomide have been approved for use among patients with MM. These agents have been increasingly used as maintenance therapy. To date, only two randomized controlled trials of maintenance therapy have examined the efficacy of these novel agents head-to-head. Here, we conduct a network meta-analysis of bortezomib, lenalidomide, and thalidomide to determine which of these novel agents could potentially increase overall survival (OS) and progression-free survival (PFS). Methods: A comprehensive literature search of MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and meetings abstracts from American Society of Hematology, American Society of Clinical Oncology, European Society for Medical Oncology and European Hematology Association was undertaken to identify all phase III randomized controlled trials (RCTs) of maintenance therapy published until July 2012. We applied the Bayesian mixed treatment comparison (MTC) method under the random-effects model. The indirect comparisons were constructed from trials that have one treatment in common. For each included RCT, we calculated the hazard ratio (HR) and its corresponding standard error and used this to calculate the indirect estimates of HR and corresponding credible intervals (CrI). We also ranked the treatments according to the probability of best treatment and calculated the surface underneath the cumulative ranking curve (SUCRA). All analyses were conducted in WinBUGS 1.4.3 and Stata 11.2. Results: The network, number of trials for each comparison, and number of patients enrolled is shown in Figure 1. The network for OS was based on 12 RCTs enrolling 5542 patients and the network for PFS was constructed from 13 RCTs and 5784 patients. The MTC networks were consistent for both OS and PFS. For both OS and PFS, two comparisons were produced (Figure 2). For OS, the analysis showed that none of the treatments were superior. For PFS, lenalidomide was superior to thalidomide (HR = 0.58, 95% CrI [0.37, 0.94]). The estimates of SUCRA and rank probabilities (Figure 3) suggested that for OS bortezomib was best followed by lenalidomide and thalidomide. For PFS, lenalidomide was best followed by bortezomib and thalidomide. Conclusion: Using the MTC method, we found no evidence that any of the novel agents are superior to one another in terms of OS. Lenalidomide was the only novel agent which was superior to another active therapy (thalidomide). While these results provide preliminary evidence to which novel agent may be more beneficial as maintenance therapy, definitive conclusions cannot be reached until large, well designed RCTs evaluating these therapies head-to-head are conducted. Disclosures: No relevant conflicts of interest to declare.


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