scholarly journals Ivermectin for Prevention and Treatment of COVID-19 Infection: a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Andrew Bryant ◽  
Theresa A Lawrie ◽  
Therese Dowswell ◽  
Edmund Fordham ◽  
Scott Mitchell ◽  
...  
Keyword(s):  
Low Cost ◽  
Meta Analysis ◽  
Severe Disease ◽  
Risk Of Bias ◽  
Bibliographic Databases ◽  
Average Risk ◽  
Risk Of Death ◽  
Secondary Outcomes ◽  
Meta Analyses ◽  
Grade Approach

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.

scholarly journals Ivermectin for prevention and treatment of COVID-19 infection: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Andrew Bryant ◽  
Theresa A Lawrie ◽  
Therese Dowswell ◽  
Edmund Fordham ◽  
Mitchell Scott ◽  
...  
Keyword(s):  
Low Cost ◽  
Meta Analysis ◽  
Severe Disease ◽  
Risk Of Bias ◽  
Bibliographic Databases ◽  
Average Risk ◽  
Risk Of Death ◽  
Secondary Outcomes ◽  
Meta Analyses ◽  
Reduced Risk

BackgroundRe-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.MethodsWe 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 the GRADE approach.FindingsTwenty-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.InterpretationLow 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.FundingNoneKeywords: ivermectin, prophylaxis, prevention treatment, covid-19, SARS-CoV-2

scholarly journals Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis and trial sequential analysis to inform clinical guidelines

2021 ◽  
Author(s):  
Andrew Bryant ◽  
Theresa A Lawrie ◽  
Therese Dowswell ◽  
Edmund J. Fordham ◽  
Mitchell Scott ◽  
...  
Keyword(s):  
Sequential Analysis ◽  
Low Cost ◽  
Meta Analysis ◽  
Severe Disease ◽  
Bibliographic Databases ◽  
Trial Sequential Analysis ◽  
Average Risk ◽  
Risk Of Death ◽  
Secondary Outcomes ◽  
Meta Analyses

Background Re-purposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with anti-viral and anti-inflammatory properties, has now been tested in numerous clinical trials.Areas of uncertainty We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemo-prophylaxis, among people with, or at high risk of, covid-19 infection. Data sourcesWe searched bibliographic databases up to April 25 2021. 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 the GRADE approach and additionally in trial sequential analyses for mortality.Twenty-four RCTs involving 3406 participants met review inclusion. Therapeutic Advances Meta-analysis of 15 trials found ivermectin reduced risk of death compared with no ivermectin (average Risk Ratio 0.38, 95% confidence interval (CI) 0.19 to 0.73; n=2438; I2=49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis (TSA) using the same DerSimonian-Laird method that underpinned the unadjusted analysis. This was also robust against a TSA using the Biggerstaff-Tweedie method. Low-certainty evidence found ivermectin prophylaxis reduced covid-19 infection by an average 86% (95% CI 79% to 91%). Secondary outcomes provided less certain evidence. Low certainty evidence suggested that that there may be no benefit with ivermectin for ‘need for mechanical ventilation’, whereas effect estimates for ‘improvement’ and ‘deterioration’ clearly favoured ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty.Conclusions Moderate-certainty evidence finds that large reductions in covid-19 deaths are possible using ivermectin. Employing ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

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

2021 ◽  
Author(s):  
Dena Zeraatkar ◽  
Ellen Cusano ◽  
Juan Pablo Diaz Martinez ◽  
Anila Qasim ◽  
Sophia O Mangala ◽  
...  
Keyword(s):  
Systematic Review ◽  
Standard Care ◽  
Meta Analysis ◽  
Analysis Data ◽  
Risk Of Bias ◽  
Risk Of Death ◽  
Study Selection ◽  
Receptor Blockers ◽  
Meta Analyses ◽  
Grade Approach

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.

scholarly journals Temporal trends of sex differences for COVID-19 infection, hospitalisation, severe disease, intensive care unit (ICU) admission and death: a meta-analysis of 229 studies covering over 10M patients

F1000Research ◽  
2022 ◽  
Vol 11 ◽  
pp. 5
Author(s):  
Bart G. Pijls ◽  
Shahab Jolani ◽  
Anique Atherley ◽  
Janna I.R. Dijkstra ◽  
Gregor H.L. Franssen ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Disease Severity ◽  
Meta Analysis ◽  
Severe Disease ◽  
Temporal Trends ◽  
Icu Admission ◽  
Risk Of Death ◽  
Relative Risks ◽  
Meta Analyses

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020)

scholarly journals Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e044640 ◽  
Author(s):  
Bart G Pijls ◽  
Shahab Jolani ◽  
Anique Atherley ◽  
Raissa T Derckx ◽  
Janna I R Dijkstra ◽  
...  
Keyword(s):  
Intensive Care ◽  
Data Extraction ◽  
Meta Analysis ◽  
Severe Disease ◽  
Case Control Studies ◽  
Icu Admission ◽  
Risk Of Death ◽  
Demographic Risk ◽  
Meta Analyses ◽  
Age And Sex

ObjectiveWe aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death.DesignSystematic review and meta-analysis.Data sourcesPubMed and Embase through 4 May 2020.Study selectionWe considered cohort and case–control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death.Data extraction and synthesisWe screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale.ResultsWe screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years.ConclusionsMeta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death.PROSPERO registration numberCRD42020180085.

scholarly journals Protocol: Benefits and harms of remdesivir for COVID-19 in adults: A systematic review with meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260544
Author(s):  
Asger Sand Paludan-Müller ◽  
Andreas Lundh ◽  
Matthew J. Page ◽  
Klaus Munkholm
Keyword(s):  
Systematic Review ◽  
Health Care ◽  
Adverse Events ◽  
Meta Analysis ◽  
Severe Disease ◽  
Risk Of Bias ◽  
Bibliographic Databases ◽  
Selective Reporting ◽  
Randomised Trials ◽  
Study Results

Background Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir showed promising results in early randomised trials but subsequently a large publicly funded trial has shown less favourable results and the evidence is interpreted differently in clinical guidelines. Systematic reviews of remdesivir have been published, but none have systematically searched for unpublished data, including regulatory documents, and assessed the risk of bias due to missing evidence. Methods We will conduct a systematic review of randomised trials comparing remdesivir to placebo or standard of care in any setting. We will include trials regardless of the severity of disease and we will include trials examining remdesivir for indications other than Covid-19 for harms analyses. We will search websites of regulatory agencies, trial registries, bibliographic databases, preprint servers and contact trial sponsors to obtain all available data, including unpublished clinical data, for all eligible trials. Our primary outcomes will be all-cause mortality and serious adverse events. Our secondary outcomes will be length of hospital stay, time to death, severe disease, and adverse events. We will assess the risk of bias using the Cochranes Risk of Bias 2 tool and the risk of bias due to missing evidence (e.g. publication bias, selective reporting bias) using the ROB-ME tool. Where appropriate we will synthesise study results by conducting random-effects meta-analysis. We will present our findings in a Summary of Findings table and rate the certainty of the evidence using the GRADE approach. Discussion By conducting a comprehensive systematic review including unpublished data (where available), we expect to be able to provide valuable information for patients and clinicians about the benefits and harms of remdesivir for the treatment of Covid-19. This will help to ensure optimal treatment for individual patients and optimal utilisation of health care resources. Systematic review registration CRD42021255915.

scholarly journals Differentiating PSP from MSA using MR planimetric measurements: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Beatrice Heim ◽  
Florian Krismer ◽  
Klaus Seppi
Keyword(s):  
Sensitivity And Specificity ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Index Test ◽  
Study Quality ◽  
Parkinsonian Syndromes ◽  
Quantitative Mr ◽  
Meta Analyses ◽  
Planimetric Measurements

AbstractDifferential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology. Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP-parkinsonism. Several studies have used midbrain to pons ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing PSP patients from those with Parkinson's disease. The current meta-analysis aimed to compare the performance of these measures in discriminating PSP from multiple system atrophy (MSA). A systematic MEDLINE review identified 59 out of 2984 studies allowing a calculation of sensitivity and specificity using the MRPI or M/P. Meta-analyses of results were carried out using random effects modelling. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eight studies were suitable for analysis. The meta‐analysis showed a pooled sensitivity and specificity for the MRPI of PSP versus MSA of 79.2% (95% CI 72.7–84.4%) and 91.2% (95% CI 79.5–96.5%), and 84.1% (95% CI 77.2–89.2%) and 89.2% (95% CI 81.8–93.8%), respectively, for the M/P. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection and index test, as all patients were seen in a specialized outpatient department without avoiding case control design and no predefined threshold was given regarding MRPI or M/P cut-offs. Planimetric brainstem measurements, in special the MRPI and M/P, yield high diagnostic accuracy for the discrimination of PSP from MSA. However, there is an urgent need for well-designed, prospective validation studies to ameliorate the concerns regarding the risk of bias.

scholarly journals Comparative efficacy and safety of interventions for treating head lice: a protocol for systematic review and network meta-analysis

2021 ◽  
Vol 5 (1) ◽  
pp. e001129
Author(s):  
Bill Stevenson ◽  
Wubshet Tesfaye ◽  
Julia Christenson ◽  
Cynthia Mathew ◽  
Solomon Abrha ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Grey Literature ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Head Lice ◽  
Efficacy And Safety ◽  
Randomised Controlled ◽  
Meta Analyses

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.

scholarly journals Predictability of rotational tooth movement with orthodontic aligners comparing software-based and achieved data: A systematic review and meta-analysis of observational studies

2021 ◽  
pp. 146531252110272
Author(s):  
Despina Koletsi ◽  
Anna Iliadi ◽  
Theodore Eliades
Keyword(s):  
Effect Size ◽  
Tooth Movement ◽  
Data Extraction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Patient Treatment ◽  
Qualitative Synthesis ◽  
Meta Analyses ◽  
Enamel Reduction

Objective: To evaluate all available evidence on the prediction of rotational tooth movements with aligners. Data sources: Seven databases of published and unpublished literature were searched up to 4 August 2020 for eligible studies. Data selection: Studies were deemed eligible if they included evaluation of rotational tooth movement with any type of aligner, through the comparison of software-based and actually achieved data after patient treatment. Data extraction and data synthesis: Data extraction was done independently and in duplicate and risk of bias assessment was performed with the use of the QUADAS-2 tool. Random effects meta-analyses with effect sizes and their 95% confidence intervals (CIs) were performed and the quality of the evidence was assessed through GRADE. Results: Seven articles were included in the qualitative synthesis, of which three contributed to meta-analyses. Overall results revealed a non-accurate prediction of the outcome for the software-based data, irrespective of the use of attachments or interproximal enamel reduction (IPR). Maxillary canines demonstrated the lowest percentage accuracy for rotational tooth movement (three studies: effect size = 47.9%; 95% CI = 27.2–69.5; P < 0.001), although high levels of heterogeneity were identified (I2: 86.9%; P < 0.001). Contrary, mandibular incisors presented the highest percentage accuracy for predicted rotational movement (two studies: effect size = 70.7%; 95% CI = 58.9–82.5; P < 0.001; I2: 0.0%; P = 0.48). Risk of bias was unclear to low overall, while quality of the evidence ranged from low to moderate. Conclusion: Allowing for all identified caveats, prediction of rotational tooth movements with aligner treatment does not appear accurate, especially for canines. Careful selection of patients and malocclusions for aligner treatment decisions remain challenging.

scholarly journals Influence of Coronal Preflaring on the Accuracy of Electronic Working Length Determination: Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (13) ◽  
pp. 2760
Author(s):  
María León-López ◽  
Daniel Cabanillas-Balsera ◽  
Victoria Areal-Quecuty ◽  
Jenifer Martín-González ◽  
María C. Jiménez-Sánchez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Science Studies ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Permanent Teeth ◽  
Total Risk ◽  
Human Teeth ◽  
Working Length ◽  
Meta Analyses

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.

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