Use of Living Systematic Reviews (LSRS) Beyond COVID-19

Objectives: A LSR is a systematic review that is continually updated, incorporating new evidence as it becomes available. They are conducted in research areas where new evidence is constantly emerging on diagnostic methods, treatments, and outcomes. The objective of this study was to understand the current application of LSRs across research areas. Method(s): Embase, MEDLINE, and the Cochrane Database of Systematic Reviews were searched to identify LSRs. Only the most recent update of a LSR was included. Data regarding the indication, intervention, methods, frequency of updates, and funding were extracted. Result(s): Of the 1,243 records identified, 126 LSRs were included for analysis. The first LSR was published in 2015, with a significant increase in the number of LSRs published starting in 2020, coinciding with the COVID-19 pandemic. The most common indication represented by LSRs was COVID-19 (72%), followed by oncology (10%). Other indications with LSRs included chronic pain, traumatic brain injury, and skin disorders, among others. While most oncology LSRs identified interventional randomized-controlled trials (RCTs) (85%), only 54% of COVID-19 LSRs were restricted to interventional studies, including a combination of RCTS and real-world observational studies. Oncology LSRs included common cancers such as prostate, renal, or multiple myeloma. Of the reviews that reported update frequency, 28% planned monthly, 12% yearly, and 12% weekly updates. Only 46% of LSRs were registered. The majority of LSRs were funded by government or research organizations. Objectives of LSRs varied, with most stating the need to maintain up-to-date databases;however, several studies used LSRs to facilitate network meta-analysis or mixed treatment comparisons. Conclusion(s): While LSRs were introduced over five years ago, their frequency increased during the COVID-19 pandemic. Apart from COVID-19, LSRs are commonly used in oncology settings. LSRs provide high-level, relevant, and up-to-date evidence, making them a useful tool for clinical and real-world research.Copyright © 2023

A multifaceted graphical display, including treatment ranking, was developed to aid interpretation of network meta-analysis.

OBJECTIVES: Network meta-analysis (NMA) is becoming a popular statistical tool for analyzing a network of evidence comparing more than two interventions. A particular advantage of NMA over pairwise meta-analysis is its ability to simultaneously compare multiple interventions including comparisons not previously trialed together, permitting intervention hierarchies to be created. Our aim was to develop a novel graphical display to aid interpretation of NMA to clinicians and decision-makers that incorporates ranking of interventions. STUDY DESIGN AND SETTING: Current literature was searched, scrutinized, and provided direction for developing the novel graphical display. Ranking results were often found to be misinterpreted when presented alone and, to aid interpretation and effective communication to inform optimal decision-making, need to be displayed alongside other important aspects of the analysis including the evidence networks and relative intervention effect estimates. RESULTS: Two new ranking visualizations were developed-the 'Litmus Rank-O-Gram' and the 'Radial SUCRA' plot-and embedded within a novel multipanel graphical display programmed within the MetaInsight application, with user feedback gained. CONCLUSION: This display was designed to improve the reporting, and facilitate a holistic understanding, of NMA results. We believe uptake of the display would lead to better understanding of complex results and improve future decision-making.

Comparison of the efficacy and comfort of high-flow nasal cannula with different initial flow settings in patients with acute hypoxemic respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) has been proven effective in improving patients with acute hypoxemic respiratory failure (AHRF), but a discussion of its use for initial flow settings still need to be provided. We aimed to compare the effectiveness and comfort evaluation of HFNC with different initial flow settings in patients with AHRF. METHODS: Studies published by October 10, 2022, were searched exhaustively in PubMed, Embase, Web of Science, Cochrane Library (CENTRAL), and the China National Knowledge Infrastructure (CNKI) database. Network meta-analysis (NMA) was performed with STATA 17.0 and R software (version 4.2.1). A Bayesian framework was applied for this NMA. Comparisons of competing models based on the deviance information criterion (DIC) were used to select the best model for NMA. The primary outcome is the intubation at day 28. Secondary outcomes included short-term and long-term mortality, comfort score, length of ICU or hospital stay, and 24-h PaO2/FiO2. RESULTS: This NMA included 23 randomized controlled trials (RCTs) with 5774 patients. With NIV as the control, the HFNC_high group was significantly associated with lower intubation rates (odds ratio [OR] 0.72 95% credible interval [CrI] 0.56 to 0.93; moderate quality evidence) and short-term mortality (OR 0.81 95% CrI 0.69 to 0.96; moderate quality evidence). Using HFNC_Moderate (Mod) group (mean difference [MD] - 1.98 95% CrI -3.98 to 0.01; very low quality evidence) as a comparator, the HFNC_Low group had a slight advantage in comfort scores but no statistically significant difference. Of all possible interventions, the HFNC_High group had the highest probability of being the best in reducing intubation rates (73.04%), short-term (82.74%) and long-term mortality (67.08%). While surface under the cumulative ranking curve value (SUCRA) indicated that the HFNC_Low group had the highest probability of being the best in terms of comfort scores. CONCLUSIONS: The high initial flow settings (50-60 L/min) performed better in decreasing the occurrence of intubation and mortality, albeit with poor comfort scores. Treatment of HFNC for AHRF patients ought to be initiated from moderate flow rates (30-40 L/min), and individualized flow settings can make HFNC more sensible in clinical practice.

Antithrombotic strategies in COVID-19 patients: a systematic review and Bayesian network meta-analysis

Introduction: COVID-19 is a public health emergency of international concern. Clinicians are likely to adopt various antithrombotic strategies to prevent embolic events, but the optimal antithrombotic strategy remains uncertain. We performed a Bayesian network meta-analysis to evaluate various antithrombotic strategies comprehensively. Method(s): We systematically searched PubMed, Cochrane Library, Web of Science, EMBASE and Clinical trials. gov to screen trials comparing different antithrombotic strategies. The primary outcome is 28-day mortality, and the secondary outcomes include major thrombotic event, major bleeding and in-hospital mortality, etc. We assessed the risk of bias using the Cochrane Collaboration's tool and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We successively performed traditional pairwise and Bayesian network meta-analysis using R v4.2.1 software. Result(s): Twenty-six eligible randomized controlled trials were included, giving a total of 35 paired comparisons with 32,041 patients randomized to 7 antithrombotic strategies. In comparison to standard of care (SoC) strategy, therapeutic anticoagulation (TA) (RR 0.36, 95% CrI 0.13-0.86) and prophylactic anticoagulation (PA) (RR 0.35, 95% CrI 0.12-0.85) strategy significantly reduced the mortality of COVID-19 patients (Fig. 1). The antiplatelet (AP) strategy was associated with high risk of major bleeding when compared with SoC strategy (RR 2.5, 95% CrI 1.1-8.9), and the TA (RR 0.43, 95% CrI 0.17-0.98), PA (RR 0.27, 95% CrI 0.10-0.63) and PA with Fibrinolytic agents (FA) strategy (RR 0.12, 95% CrI 0.01-0.81) was associated with low risk of major thrombotic event. Conclusion(s): This network meta-analysis indicates that the TA and PA strategies probably reduce mortality and confer other important benefits in COVID-19 patients. These findings provide guidance on how to choose optimal antithrombotic strategies for COVID-19 patients.

Evaluating the reactogenicity of COVID-19 vaccines from network-meta analyses.

BACKGROUND: Evidence-based reassurances addressing vaccine-related concerns are crucial to promoting primary vaccination, completion of the primary series, and booster vaccination. By summarizing and comparing the reactogenicity of COVID-19 vaccines authorized by the European Medicines Agency, this analysis aims to support in-formed decision-making by the lay public and help overcome vaccine hesitancy. RESEARCH DESIGN AND METHODS: A systematic literature review identified 24 records reporting solicited adverse events for AZD1222, BNT162b2, mRNA-1273, NVX-Cov2373, and VLA2001 in individuals aged 16 or older. Network meta-analyses were conducted for each solicited adverse events reported for at least two vaccines that were not compared head-to-head but could be connected through a common comparator. RESULTS: A total of 56 adverse events were investigated through network meta-analyses within a Bayesian framework with random-effects models. Overall, the two mRNA vaccines were found to be the most reactogenic vaccines. VLA2001 had the highest likelihood of being the least reactogenic vaccine after the first and second vaccine dose, especially for systemic adverse events after the first dose. CONCLUSIONS: The reduced chance of experiencing an adverse event with some COVID-19 vaccines may help to overcome vaccine hesitancy in population groups with concerns about the side effects of vaccines.

Evaluation of dressings preventing facial medical device-related pressure injury in medical staff during the COVID-19 pandemic: A systematic review and network meta-analysis.

AIM: This study systematically compared the efficacy of various dressings that may prevent facial medical device-related pressure injury (MRDPI) in medical staff during the COVID-19 pandemic. BACKGROUND: During the COVID-19 pandemic, medical staff who are required to wear masks, goggles and other personal protective equipment (PPE) are susceptible to facial MRDPI, which exacerbates working conditions. Dressings can effectively prevent or alleviate MRDPI, but it is unclear which dressings are most effective. DESIGN: A systematic review and network meta-analysis, in accordance with PRISMA. METHODS: A comprehensive literature search was conducted in four English and four Chinese databases to identify relevant studies published up to 8 September 2022. The selected studies were randomised controlled trials, with populations comprising medical staff who wore PPE during the COVID-19 pandemic and included an observation and control group. RESULTS: The network meta-analysis of the 12 selected articles showed that foam dressing, hydrocolloid dressing and petrolatum gauze were better than conventional protection for preventing MRDPI. The surface under the cumulative ranking curve indicated that foam dressing was the best preventative. CONCLUSION: Foam dressing is more effective than other dressings in preventing facial MRDPI in medical staff. When PPE must be worn for many hours, such as during the COVID-19 pandemic, medical staff can use foam dressings to prevent MRDPI. RELEVANCE TO CLINICAL PRACTICE: The results support the use of dressings, especially foam dressings, to prevent MRDPI in healthcare workers. The appropriate dressings are recommended to prevent MRDPI associated with wearing PPE.

comparative effectiveness of remotely delivered biopsychosocial interventions for the treatment of osteoarthritic pain. A network meta - analysis

Purpose: Osteoarthritis (OA) can cause pain, discomfort, stiffness and progressively limit your ability to perform everyday tasks. Currently, there is no cure for OA, hence most patients experience chronic pain. Evidence suggests a shared mechanism between chronic pain and mental disorders. Patients living with OA- related chronic pain and depression have complex needs due to high rates of persistent physical and mental health symptoms, issues around inadequate pain relief, risks with opioid use, frequent lack of access to primary care, 80% unemployment rates, and complicated family/social relationships. Thus, they require physical, cognitive, and social treatments delivered by a multidisciplinary team that integrates physical and mental health approaches. The pandemic posed a major challenge for patients with osteoarthritis. Public health measures postponed non-emergency in-person treatment programs. People suffering from osteoarthritis are typically older which makes them more vulnerable to SARS-COV-2 infection. Telemedicine is a method that enables remote or virtual appointments between patients and health care practitioner. While remote care offers a wide range of benefits it is unclear if these interventions can provide similar effects with face-to-face care. In this study, we aimed to evaluate the effectiveness of remote biopsychosocial interventions in comparison to sham, traditional, or alternative remote treatments in patients with osteoarthritic pain and mental health symptoms using a network meta-analysis approach. Method(s): Eligible studies were randomized trials of remote biopsychosocial interventions that included at least one treatment arm provided remotely/virtually and compared to an alternative (sham, non-intervention, face-to-face treatment or alternative virtual/remote intervention). Patients had OA-related chronic musculoskeletal pain and at least 60% of participants had a mental health comorbidity or the analysis was disaggregated by mental health comorbidity. The primary outcome of interest was pain intensity at 12-weeks follow-up. Secondary outcomes were depression levels, dropouts/withdrawals and any adverse or serious adverse events reported. Potential mediators extracted were patient characteristics such as mean age, sex/gender and duration of symptoms/follow-up. We extracted data from the closest timepoint to 12-weeks follow-up for all outcomes. We critically appraised the included trials with the Cochrane risk of bias tool. Effect estimates were presented as standardized mean differences (SMD) and were comparisons between remote interventions and wait-list control. For all estimates, we reported the medians with corresponding 95% credibility intervals (CrIs) from the 2.5th and 97.5th percentile of the posterior distribution. The prespecified minimal clinically important between-group difference was -0.37 SD units. We estimated the probability of the effect of remote interventions of being superior to facilitate the interpretation of estimated treatment effects. We used a Bayesian random-effects network meta-analysis model. Analysis was conducted with OpenBUGS and STATA 16.0. Result(s): Overall, 21 trials with 4,426 patients with OA were included in this network meta-analysis. We identified 11 different interventions (combination or alone) such as usual care, exercise, education, cognitive behavioural therapy (CBT) guided or unguided delivered in different remote formats (internet, tele, mobile application or face-to-face). At 12-weeks follow-up, internet-delivered exercise (SMD -0.25, 95%Crl -0.59 to -0.09), Tele-CBT (SMD -0.22, 95%Crl -0.56 to 0.12) and a combination of Tele-CBT with education plus exercise (SMD -0.25, 95%Crl -0.66 to 0.15) had more pronounced treatment effects on pain reduction compared to wait-list control and 94%, 92% and 90% probability of being superior (respectively). For depression outcomes, a combination of tele-CBT with education plus exercise, had more pronounced treatment effects (SMD -0.31 95%Crl -1.16 to 0.53) when compared to wait-list-control and 86% pr bability of being superior. Conclusion(s): Internet-delivered exercise, Tele-CBT, and a combination of Tele-CBT with education plus exercise displayed higher probability of being superior than the other interventions, and had more pronounced effects in reducing pain intensity and depression levels when compared to wait-list control. However, none of these interventions excluded the null threshold.Copyright © 2023

Higher versus lower dose corticosteroids for moderate to severe COVID-19: a systematic review, dose response and network meta-analysis

Background: Corticosteroids are standard of care for moderate-to-severe COVID-19. However, the optimal dosing is unclear. Our objective was to compare higher dose corticosteroids to lower dose corticosteroids in patients with moderate-to-severe COVID-19. Method(s): We searched for randomized trials of adult patients with moderate-to-severe COVID-19 that compared corticosteroids versus placebo, standard care or that compared alternative doses of corticosteroids. We performed both a frequentist network and dose-response meta-analysis. We assessed risk of bias using a modified version of the Cochrane RoB 2.0 and used GRADE to assess the certainty of evidence. Result(s): We included 21 randomized trials with 9,640 patients. Our dose response analysis found that higher dose corticosteroids probably reduce mortality compared to lower dose (risk difference 13 fewer deaths per 1000 (95% CI 22.6 to 3.92 fewer);moderate certainty), may decrease the need of mechanical ventilation dose (risk difference 10 fewer per 1000 (95% CI 20.5 to 4.8 fewer) and probably decreases risk of infections (16.7 fewer infections per 1000 (95% CI 25 to 5.4 fewer);moderate certainty). Our network meta-analysis found that high dose corticosteroids probably reduce the duration of mechanical ventilation as compared to low dose (6.9 fewer days (95% CI 8.5 to 5.2 fewer);moderate certainty). The results of our network and dose response analysis were consistent. Conclusion(s): High dose corticosteroids is more effective than than low dose in reducing mortality.

Pairwise and Network Meta-Analysis of Antiviral and other Treatment Efficacy in Covid-19 Patients

A total of 77 literatures till November 2020 were screened regarding various interventions to treat COVID-19 patients, among which 16 and 15 studies fulfilling predefined exclusion and inclusion criteria were subjected to Pairwise and Network meta-analysis respectively. In Pairwise meta-analysis, the recovery rate of treatment with Lopinavir/Ritonavir versus other antiviral (OR= 0. 0381, CI= 0.0021-0.6870), placebo (OR= 0.6592, CI= 0.4207-1. 0329), Remdesivir (OR= 0.5286, CI= 0.3915-0.7137) and standard care (OR= 0.9787, CI= 0.8523-1.1238) in fixed and random effect model with 95% confidence limit found statistically significant protection than those of all other treatment. In Network meta-analysis, recovery estimates sizes of treatment, in reference with other antivirals 1.0000 (0.9917, 1.0000) shows less risk with treatment Standard care 0.7811 (0.6696, 0.8417), Remdesivir 0.7717 (0.6491, 0.8144), Lopinavir/ Ritonavir 0.7801 (0.6701, 0.8473), Placebo 0.7219 (0.6178, 0.7836).Copyright © 2023, Institute of Medico-legal Publication. All rights reserved.

CBT treatment delivery formats for panic disorder: a systematic review and network meta-analysis of randomised controlled trials.

Several in-person and remote delivery formats of cognitive-behavioural therapy (CBT) for panic disorder are available, but up-to-date and comprehensive evidence on their comparative efficacy and acceptability is lacking. Our aim was to evaluate the comparative efficacy and acceptability of all CBT delivery formats to treat panic disorder. To answer our question we performed a systematic review and network meta-analysis of randomised controlled trials. We searched MEDLINE, Embase, PsycINFO, and CENTRAL, from inception to 1st January 2022. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO. We found a total of 74 trials with 6699 participants. Evidence suggests that face-to-face group [standardised mean differences (s.m.d.) -0.47, 95% confidence interval (CI) -0.87 to -0.07; CINeMA = moderate], face-to-face individual (s.m.d. -0.43, 95% CI -0.70 to -0.15; CINeMA = Moderate), and guided self-help (SMD -0.42, 95% CI -0.77 to -0.07; CINeMA = low), are superior to treatment as usual in terms of efficacy, whilst unguided self-help is not (SMD -0.21, 95% CI -0.58 to -0.16; CINeMA = low). In terms of acceptability (i.e. all-cause discontinuation from the trial) CBT delivery formats did not differ significantly from each other. Our findings are clear in that there are no efficacy differences between CBT delivered as guided self-help, or in the face-to-face individual or group format in the treatment of panic disorder. No CBT delivery format provided high confidence in the evidence at the CINeMA evaluation.

Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis.

Background: JAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors and the optimum thereof for COVID-19 have not been adequately defined. Methods: Databases were searched from their inception dates to 17 June 2022. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. The primary outcome was the coefficient of mortality. Results: Twenty-eight studies of 8,206 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). A pairwise meta-analysis revealed that JAK inhibitors effectively reduced the mortality (OR = 0.54; 95% CI: 0.46-0.63; P < 0.00001; I 2 = 32%) without increasing the risk of adverse events (OR = 1.02; 95% CI: 0.88-1.18; P = 0.79; I 2 = 12%). In a network meta-analysis, clinical efficacy benefits were seen among different types of JAK inhibitors (baricitinib, ruxolitinib, and tofacitinib) without the observation of a declined incidence of adverse events. The assessment of rank probabilities indicated that ruxolitinib presented the greatest likelihood of benefits regarding mortality and adverse events. Conclusion: JAK inhibitors appear to be a promising treatment for COVID-19 concerning reducing mortality, and they do not increase the risk of adverse events vs. standard of care. A network meta-analysis suggests that mortality benefits are associated with specific JAK inhibitors, and among these, ruxolitinib presents the greatest likelihood of having benefits for mortality and adverse events. Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42022343338].

Traditional Chinese Medicine for COVID-19: A Network Meta-Analysis and Systematic Review.

To compare the efficacy of different traditional Chinese medicine (TCM) therapies for the treatment of coronavirus disease 2019 (COVID-19) and provide a higher level of evidence in the form of network meta-analysis (NMA) and systematic review. We searched the studies from the following databases: CNKI, VIP, WanFang, SinoMed, PubMed, Embase, and Web of Science from the establishment of the respective database until December 2021. Relevant studies were screened according to the pre-established inclusion criteria. The quality of the included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) were assessed using the risk of bias (ROB) tool and the Methodological Index for Non-Randomized Studies (MINORS), respectively. R software 4.1.1 and Stata 13.1 were used for data analysis and mapping. A total of 34 studies were included in this network meta-analysis that tested 24 TCM interventions and included 3443 patients. Using cluster analysis of time to negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), the length of hospital stay and composite events, we found that Jinyinhua oral liquid (JYH, 120 mL) + conventional Western medicine (CWM) has the highest SUCRA value at 88.64%, 85.61% and 84.24%. The traditional meta-analysis results revealed that Qingfei Paidu decoction + CWM were significantly different compared with CWM alone for the score of clinical symptoms (MD =-0.75, 95% CI [-1.04, -0.47]). Nine studies reported 57 adverse reactions (ADRs) and 3 adverse events (ADEs) in TCM + CWM groups, and eight studies reported 33 ADRs and 8 ADEs in CWM groups. In conclusion, the combination of TCM and CWM approaches may enhance the efficacy of CWM in COVID-19 patients. Based on the NMA result, JYH (120 mL) + CWM may be a more effective treatment and deserves further investigation. However, the differences in many comparisons between TCM interventions did not reach statistical significance; therefore, further high-quality studies are required to validate these findings.

Rapid antigen-based and rapid molecular tests for the detection of SARS-CoV-2: a rapid review with network meta-analysis of diagnostic test accuracy studies.

BACKGROUND: The global spread of COVID-19 created an explosion in rapid tests with results in < 1 hour, but their relative performance characteristics are not fully understood yet. Our aim was to determine the most sensitive and specific rapid test for the diagnosis of SARS-CoV-2. METHODS: Design: Rapid review and diagnostic test accuracy network meta-analysis (DTA-NMA). ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies assessing rapid antigen and/or rapid molecular test(s) to detect SARS-CoV-2 in participants of any age, suspected or not with SARS-CoV-2 infection. INFORMATION SOURCES: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials, up to September 12, 2021. OUTCOME MEASURES: Sensitivity and specificity of rapid antigen and molecular tests suitable for detecting SARS-CoV-2. Data extraction and risk of bias assessment: Screening of literature search results was conducted by one reviewer; data abstraction was completed by one reviewer and independently verified by a second reviewer. Risk of bias was not assessed in the included studies. DATA SYNTHESIS: Random-effects meta-analysis and DTA-NMA. RESULTS: We included 93 studies (reported in 88 articles) relating to 36 rapid antigen tests in 104,961 participants and 23 rapid molecular tests in 10,449 participants. Overall, rapid antigen tests had a sensitivity of 0.75 (95% confidence interval 0.70-0.79) and specificity of 0.99 (0.98-0.99). Rapid antigen test sensitivity was higher when nasal or combined samples (e.g., combinations of nose, throat, mouth, or saliva samples) were used, but lower when nasopharyngeal samples were used, and in those classified as asymptomatic at the time of testing. Rapid molecular tests may result in fewer false negatives than rapid antigen tests (sensitivity: 0.93, 0.88-0.96; specificity: 0.98, 0.97-0.99). The tests with the highest sensitivity and specificity estimates were the Xpert Xpress rapid molecular test by Cepheid (sensitivity: 0.99, 0.83-1.00; specificity: 0.97, 0.69-1.00) among the 23 commercial rapid molecular tests and the COVID-VIRO test by AAZ-LMB (sensitivity: 0.93, 0.48-0.99; specificity: 0.98, 0.44-1.00) among the 36 rapid antigen tests we examined. CONCLUSIONS: Rapid molecular tests were associated with both high sensitivity and specificity, while rapid antigen tests were mainly associated with high specificity, according to the minimum performance requirements by WHO and Health Canada. Our rapid review was limited to English, peer-reviewed published results of commercial tests, and study risk of bias was not assessed. A full systematic review is required. REVIEW REGISTRATION: PROSPERO CRD42021289712.

The life and death of living systematic reviews: a methodological survey.

OBJECTIVES: The objectives of this study are to describe the characteristics of living systematic reviews (LSRs) and to understand their life cycles. STUDY DESIGN AND SETTING: We conducted a comprehensive search up to April 2021 then selected articles and abstracted data in duplicate and independently. We undertook descriptive analyses and calculated delay in version update and delay since the last published version. RESULTS: We included 76 eligible LSRs with a total of 279 eligible versions. The majority of LSRs was from the clinical field (70%), was COVID-19 related (63%), and had a funding source specified (62%). The median number of versions per LSR was 2 (interquartile range (IQR) 1-4; range 1-19). The median and IQR for the ratio of the actual period of update to the planned period of update was 1.12 (0.81; 1.71). Out of all reviews with a 'planned period of update' and at least one update (N = 19), eight LSRs (42%) had a period since last published version greater than 3 times the planned period of update. No LSR included a 'retirement notice' in their latest published version. CONCLUSION: While most LSR complied with the planned period of producing updates, a substantive proportion lagged since their last update.

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis.

PURPOSE: To assess and compare the relative efficacy and safety of anti-SARS-CoV-2 antibody regimens for COVID-19. METHODS: This systematic review and random-effects network meta-analysis was conducted according to PRISMA-NMA. Literature searches were conducted across MEDLINE, EMBASE, PubMed, Web of Science, CENTRAL, and CNKI up to February 20th, 2022. Interventions were ranked using P scores. RESULTS: Fifty-five RCTs (N = 45,005) were included in the review. Bamlanivimab + etesevimab (OR 0.13, 95% CI 0.02-0.77) was associated with a significant reduction in mortality compared to standard of care/placebo. Casirivimab + imdevimab reduced mortality (OR 0.67, 95% CI 0.50-0.91) in baseline seronegative patients only. Four different regimens led to a significant decrease in the incidence of hospitalization compared to standard of care/placebo with sotrovimab ranking first in terms of efficacy (OR 0.20, 95% CI 0.08-0.48). No treatment improved incidence of mechanical ventilation, duration of hospital/ICU stay, and time to viral clearance. Convalescent plasma and anti-COVID IVIg both led to a significant increase in adverse events compared to standard of care/placebo, but no treatment increased the odds of serious adverse events. CONCLUSION: Anti-SARS-CoV-2 mAbs are safe, and could be effective in improving mortality and incidence of hospitalization. Convalescent plasma and anti-COVID IVIg were not efficacious and could increase odds of adverse events. Future trials should further examine the effect of baseline seronegativity, disease severity, patient risk factors, and SARS-CoV-2 strain variation on the efficacy of these regimes. REGISTRATION: PROSPERO-CRD42021289903.

Executive protocol designed for new review study called: systematic review and artificial intelligence network meta-analysis (RAIN) with the first application for COVID-19.

Artificial intelligence (AI) as a suite of technologies can complement systematic review and meta-analysis studies and answer questions that cannot be typically answered using traditional review protocols and reporting methods. The purpose of this protocol is to introduce a new protocol to complete systematic review and meta-analysis studies.In this work, systematic review, meta-analysis, and meta-analysis network based on selected AI technique, and for P < 0.05 are followed, with a view to responding to questions and challenges that the global population is facing in light of the COVID-19 pandemic.Finally, it is expected that conducting reviews by following the proposed protocol can provide suitable answers to some of the research questions raised due to COVID-19.

Efficacy and safety of traditional Chinese medicine and antiviral antibody therapies for COVID-19: a network meta-analysis

Objective To systematically review the efficacy and safety of traditional Chinese medicine (TCM) and antiviral antibody therapy in the treatment of COVID-19. Methods PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data, VIP and SinoMED databases were electronically searched to collect randomized controlled trials (RCTs) on efficacy and safety of traditional Chinese medicine and antiviral antibody therapies for COVID-19 from inception to June 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies;then, network meta-analysis was performed by using Stata 14.0 software. Results A total of 44 RCTs were included. The results of network meta-analysis showed that, for mortality rate, the rank of cumulative probability was: TCM+ standard care (SC) (100%)>convalescent plasma (CP)+SC (42%)>SC (8%). In terms of hospital stay time, the rank of cumulative probability was: TCM+SC (95.5%)>SC (31.4%)>CP+SC (23.2%). In terms of time to viral clearance, the rank of cumulative probability was: TCM+SC (97.4%)>SC (37.4%)>CP+SC (15.2%). In the aspect of mechanical ventilation rate, the rank of cumulative probability was: TCM+SC (98.9%)>CP+SC (42.9%)>SC (8.3%). In the aspect of adverse reactions/events, the rank of cumulative probability was: TCM+SC (99.9%)>SC (47.9%)>CP+SC (2.2%). Conclusion The current evidence shows that TCM combined with SC is the most effective treatment in reducing mortality, shortening hospitalization time and viral negative conversion time, reducing mechanical ventilation rate, and the incidence of adverse reactions/events is low. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion. Copyright © 2022 West China University of Medical Science. All rights reserved.

Efficacy of different anticoagulant doses for patients with COVID-19: a systematic review and network meta-analysis.

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).

Efficacy of COVID-19 vaccines: a systematic review and network meta-analysis of phase 3 randomized controlled trials.

Several vaccines have been approved for the prevention of COVID-19. However, no head-to-head trials comparing their clinical efficacy have been performed. This network meta-analysis aims to identify those, among the competing existing vaccines, conferring the maximum protection against COVID-19. A literature search was done in Medline (via PubMed), Embase and Cochrane Library databases for phase 3 randomized controlled trials evaluating the efficacy of different COVID-19 vaccines. Search results were screened and eligible studies were included to perform a network meta-analysis in software 'R' version 4.1.2 using a random effect model. Cochrane's 'Risk of Bias tool (RoB2)' was used for quality assessment. Raw data from the included studies was used for network meta-analysis. Assessment of inconsistency was not possible as no study compared two or more vaccines directly. A forest plot for indirect comparison of various COVID-19 vaccines was obtained. Rankogram and 'P' scores were obtained to rank the vaccines based on the indirect evidence of their comparative efficacy. A total of 17 randomized controlled trials evaluating the efficacy of 16 COVID-19 vaccines, were included in the network meta-analysis. A total of 361,386 participants was included in this network meta-analysis. Overall risk of bias among included studies was of 'some concern'. All the COVID-19 vaccines had a statistically significant reduction of risk for contracting symptomatic SARS-CoV-2 in comparison to the placebo, however, the maximum protection (RR 0.05) was with BNT126b2. The indirect comparison also revealed BNT126b2 vaccine confers the highest protection against symptomatic SARS-CoV-2 infection in comparison to all others included, with a 'P' score of 0.9771 followed by mRNA-1273, rAD26 & rAD5 and NVX-CoV2373. The evidence generated from this network meta-analysis indicates the good efficacy of all the included vaccines in preventing symptomatic COVID-19 as compared to placebo. The BNT126b2 vaccine was found to provide the highest protection against symptomatic SARS-CoV-2 among all included followed by mRNA-1273, rAD26 & rAD5, NVX-CoV2373 and others.

A systematic review and Bayesian network meta-analysis for comparative safety assessment of favipiravir interventions in hospitalized COVID-19 patients.

INTRODUCTION: COVID-19 is a coronavirus-based infectious illness that was first detected at the end of 2019 in Wuhan, China. The novel virus induces severe acute respiratory syndrome (SARS-CoV-2) and has spread globally, resulting in an ongoing pandemic. There is still a lack of evidence for direct comparison of favipiravir therapy. Network meta-analysis (NMA), may incorporate direct and indirect comparisons in a pooled computation while depending on strong assumptions and premises. This study provides evidence-based recommendations on the safety of currently used clinical pharmacological treatments compared to favipiravir for COVID-19 patients. METHODOLOGY: We conducted a systematic review and Bayesian NMA. We searched the primary databases and clinical trials center for reports of short-term, randomized controlled trials (RCTs) of favipiravir for COVID-19 treatment. The primary endpoints here considered were any adverse events observed or reported during the treatment cycle with estimates of odds ratio (OR) and 95% confidence interval (CI), until November 6, 2021. RESULTS: Between January 2020 and July 2021, 908 individuals were randomly assigned to one of the seven active prescription medication regimens or placebo in this study, generating seven direct comparisons on 12 data points. The safety of favipiravir over the four clinically efficacious monotherapies or combinations including tocilizumab, arbidol, lopinavir + ritonavir, and chloroquine remained unknown due to the lack of a significant difference and the limited sample size. CONCLUSIONS: Overall, comparative rankings could assist doctors and guideline developers in decision-making. We have also concluded that the safety of favipiravir requires further attention.