scholarly journals Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

Author(s):  
Dena Zeraatkar ◽  
Ellen Cusano ◽  
Juan Pablo Diaz Martinez ◽  
Anila Qasim ◽  
Sophia O Mangala ◽  
...  

Objective: To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19. Design: Systematic review and network meta-analysis Data sources: WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses Study selection: Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. Results: We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias 2.0 tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach. We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty). Conclusion: IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 1
Author(s):  
Hye Won Lee ◽  
Lin Ang ◽  
Jung Tae Kim ◽  
Myeong Soo Lee

Background and Objectives: This review aimed to provide an updated review of evidence regarding the effects of aromatherapy in relieving symptoms of burn injuries, focusing on pain and physiological distress. Materials and Methods: Fifteen databases (including five English databases, four Korean medical databases, and four Iranian databases) and trial registries were searched for studies published between their dates of inception and July 2021. Two review authors individually performed study selection, data extraction, and risk of bias assessment, and any discrepancies were solved by a third review author. Results: Eight RCTs met our inclusion criteria and were analyzed in this updated systematic review. Our meta-analyses revealed that inhaled aromatherapy plus routine care showed beneficial effects in relieving pain after dressing, as compared to placebo plus routine care (p < 0.00001) and routine care alone (p = 0.02). Additionally, inhaled aromatherapy plus routine care (p < 0.00001) and aromatherapy massage plus routine care (p < 0.0001) also showed superior effects in calming anxiety, as compared to routine care alone. None of the included studies reported on AEs. Overall, the risk of bias across the studies was concerning. Conclusions: This updated review and synthesis of the studies had brought a more detailed understanding of the potential application of aromatherapy for easing the pain and anxiety of burn patients.


BMJ ◽  
2020 ◽  
pp. m2980 ◽  
Author(s):  
Reed AC Siemieniuk ◽  
Jessica J Bartoszko ◽  
Long Ge ◽  
Dena Zeraatkar ◽  
Ariel Izcovich ◽  
...  

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.


2021 ◽  
pp. 105381512199192
Author(s):  
Andréane Lavallée ◽  
Gwenaëlle De Clifford-Faugère ◽  
Ariane Ballard ◽  
Marilyn Aita

This systematic review and meta-analysis examined the effectiveness of parent–infant interventions for parents of preterm infants on parental sensitivity compared to standard care or active comparators. This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration ID: CRD42016047083). Database searches were performed from inception to 2020 to identify eligible randomized controlled trials. Two review authors independently selected studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias assessment tool and quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) guidelines. A total of 19 studies ( n = 2,111 participants) were included and 14 were suitable to be pooled in our primary outcome meta-analysis. Results show no significant effect of parent–infant interventions over standard care or basic educational programs, on parental sensitivity. Results may not necessarily be due to the ineffectiveness of the interventions but rather due to implementation failure or high risk of bias of included studies.


2021 ◽  
Author(s):  
Andrew Bryant ◽  
Theresa A Lawrie ◽  
Therese Dowswell ◽  
Edmund Fordham ◽  
Scott Mitchell ◽  
...  

Abstract Background Re-purposed medicines may have role in combating the SARS-CoV-2 virus. The antiparasitic medicine ivermectin, which has anti-viral and anti-inflammatory properties, has been tested in numerous clinical trials with promising results.Methods We assessed the efficacy of ivermectin treatment and/or prophylaxis among people with, or at high risk of covid-19 infection. We searched bibliographic databases up to February 2021 and two review authors sifted for studies, extracted data and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using GRADE approach.Findings Twenty-one RCTs involving 2741 participants met review inclusion. Meta-analysis of 13 trials found ivermectin reduced risk of death compared with no ivermectin (average Risk Ratio 0.32, 95% confidence interval (CI) 0.14 to 0.72; n=1892; I2=57%; low to moderate-certainty evidence. Low-certainty evidence found ivermectin prophylaxis reduced covid-19 infection by an average 86% (95% CI 79% to 91%). Secondary outcomes provided very-low or low certainty evidence. Low certainty evidence suggests that that there may be no benefit with ivermectin for ‘need for mechanical ventilation’, whereas effect estimates for ‘improvement’ and ‘deterioration’ favoured ivermectin use. Severe adverse events were rare and evidence of no difference was assessed as low to very low-certainty. Evidence on other secondary outcomes was very low certainty.Interpretation Low to moderate-certainty evidence suggests reductions in covid-19 deaths and infections may be possible by using ivermectin. Employing ivermectin early on may reduce the number of people progressing to severe disease. The apparent safety and low cost suggest that ivermectin could have an impact on the SARS-CoV-2 pandemic globally.


2021 ◽  
Vol 5 (1) ◽  
pp. e001129
Author(s):  
Bill Stevenson ◽  
Wubshet Tesfaye ◽  
Julia Christenson ◽  
Cynthia Mathew ◽  
Solomon Abrha ◽  
...  

BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment applications and misdiagnosis. Various head lice treatments with different mechanism of action have been developed and explored over the years, with limited report on systematic assessments of their efficacy and safety. This work aims to present a robust evidence summarising the interventions used in head lice.MethodThis is a systematic review and network meta-analysis which will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for network meta-analyses. Selected databases, including PubMed, Embase, MEDLINE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials exploring head lice treatments. Searches will be limited to trials published in English from database inception till 2021. Grey literature will be identified through Open Grey, AHRQ, Grey Literature Report, Grey Matters, ClinicalTrials.gov, WHO International Clinical Trials Registry and International Standard Randomised Controlled Trials Number registry. Additional studies will be sought from reference lists of included studies. Study screening, selection, data extraction and assessment of methodological quality will be undertaken by two independent reviewers, with disagreements resolved via a third reviewer. The primary outcome measure is the relative risk of cure at 7 and 14 days postinitial treatment. Secondary outcome measures may include adverse drug events, ovicidal activity, treatment compliance and acceptability, and reinfestation. Information from direct and indirect evidence will be used to generate the effect sizes (relative risk) to compare the efficacy and safety of individual head lice treatments against a common comparator (placebo and/or permethrin). Risk of bias assessment will be undertaken by two independent reviewers using the Cochrane Risk of Bias tool and the certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations guideline for network meta-analysis. All quantitative analyses will be conducted using STATA V.16.DiscussionThe evidence generated from this systematic review and meta-analysis is intended for use in evidence-driven treatment of head lice infestations and will be instrumental in informing health professionals, public health practitioners and policy-makers.PROSPERO registration numberCRD42017073375.


2021 ◽  
pp. 088506662110197
Author(s):  
Moosa Azadian ◽  
Suyee Win ◽  
Amir Abdipour ◽  
Carolyn Krystal Kim ◽  
H. Bryant Nguyen

Background: Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. Methods: This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. Results: We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. Conclusion: Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.


2021 ◽  
Vol 10 (13) ◽  
pp. 2760
Author(s):  
María León-López ◽  
Daniel Cabanillas-Balsera ◽  
Victoria Areal-Quecuty ◽  
Jenifer Martín-González ◽  
María C. Jiménez-Sánchez ◽  
...  

Aim. To conduct a systematic review and meta-analysis according to the following PICO question: in extracted human permanent teeth, does preflaring, compared with unflared canals, influence the accuracy of WL determination with EAL? Material and Methods. A systematic review was conducted according to the PRISMA checklist, using the following databases: PubMed, Science Direct, Scopus, and Web of Science. Studies related to WL determination using EAL both in preflared and unflared root canals of extracted human teeth were included. The outcome of interest was the accuracy of the electronic WL determination. A quality assessment of the included studies was performed, determining the risk of bias. The meta-analyses were calculated with the 5.4 RevMan software using the inverse variance method with random effects. PROSPERO registration: CRD42021243412. Results. Ten experimental studies fulfilled the inclusion criteria, and most of them found that preflaring increases the accuracy of the EALs in WL determination. The calculated OR was 1.98 (95% CI = 1.65–2.37; p < 0.00001; I2 = 10%), indicating that the determination of WL by EALs is almost twice as accurate in preflared canals. The accuracy of Root ZX in WL determination increases more than three times (OR = 3.25; p < 0.00001). Preflaring with Protaper files significantly increases the accuracy of EALs (OR = 1.76; p < 0.00001). The total risk of bias of the included studies was low. No obvious publication bias was observed. Conclusions. The results indicate a significant increase in the accuracy of WL determination with EAL after preflaring, doubling the percentage of exact measurements. Preflaring should be recommended as an important step during mechanical enlargement of the root canal, not only because it improves the access of the files to the canal, but also because it allows one to obtain more accurate electronic determinations of WL.


2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492


BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e024886 ◽  
Author(s):  
Klaus Munkholm ◽  
Asger Sand Paludan-Müller ◽  
Kim Boesen

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.


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