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World Journal of Surgical Oncology Jul 2020The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer.
METHODS
The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events.
RESULTS
The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34-0.53, p < 0.001; HR, 0.79, 95% CI 0.65-0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system.
CONCLUSIONS
PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.
Topics: Adenosine Diphosphate Ribose; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Prognosis
PubMed: 32622363
DOI: 10.1186/s12957-020-01931-7 -
Dyspnea and reversibility profile of P2Y₁₂ antagonists: systematic review of new antiplatelet drugs.American Journal of Cardiovascular... Aug 2014Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors. (Review)
Review
BACKGROUND
Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors.
OBJECTIVE
We aimed to review and quantify the global risk of dyspnea of recent P2Y₁₂ inhibitor drugs, and evaluate its association with the reversibility profile of P2Y₁₂ inhibitors.
METHODS
A database search (March 2013) retrieved randomized controlled trials (RCTs) comparing new antiplatelet drugs (ticagrelor, prasugrel, cangrelor, elinogrel) with clopidogrel. The primary outcome was the incidence of dyspnea. Placebo-controlled trials were excluded. Meta-analysis was performed and estimates were expressed as risk ratio (RR) and 95% confidence intervals (95% CIs). Dyspnea incidence was evaluated according to the reversibility profile of P2Y₁₂ antagonists.
RESULTS
We found eight RCTs including 41,289 patients. Prasugrel was not associated with an increased risk of dyspnea (RR 1.09, 95% CI 0.93-1.27), whereas ticagrelor (RR 1.95, 95% CI 1.37-2.77), cangrelor (RR 2.42, 95% CI 1.36-4.33), and elinogrel (RR 3.25, 95% CI 1.57-6.72) showed an increased risk of dyspnea. Reversible inhibitors significantly increased the risk of dyspnea compared with the irreversible inhibitor, prasugrel, through adjusted indirect comparison (RR 1.99, 95% CI 1.40-2.82).
CONCLUSIONS
The reversible P2Y₁₂ antagonists ticagrelor, cangrelor, and elinogrel have an increased incidence of dyspnea in increasing order when compared with irreversible P2Y₁₂ inhibitors such as clopidogrel or prasugrel.
Topics: Adenosine; Adenosine Monophosphate; Clopidogrel; Dyspnea; Humans; Incidence; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Sulfonamides; Thiophenes; Ticagrelor; Ticlopidine
PubMed: 24659260
DOI: 10.1007/s40256-014-0071-6 -
The British Journal of Nutrition Apr 2015Randomised controlled trials (RCT) testing the effects of antioxidant supplements on endothelial function (EF) have reported conflicting results. We aimed to investigate... (Meta-Analysis)
Meta-Analysis Review
Randomised controlled trials (RCT) testing the effects of antioxidant supplements on endothelial function (EF) have reported conflicting results. We aimed to investigate the effects of supplementation with antioxidant vitamins C and E on EF and to explore factors that may provide explanations for the inconsistent results. We searched four databases (MEDLINE, Embase, Cochrane Library and Scopus) from inception until May 2014 for RCT involving adult participants aged ≥18 years who were supplemented with vitamins C and E alone or in combination for more than 2 weeks and reporting changes in EF measured using flow mediated dilation or forearm blood flow. Data were pooled as standardised mean difference (SMD) and analysed using a random-effects model. Significant improvements in EF were observed in trials supplementing with vitamin C alone (500-2000 mg/d) (SMD: 0·25, 95% CI 0·02, 0·49, P=0·043) and vitamin E alone (300-1800 IU/d; 1 IU vitamin E=0·67 mg natural vitamin E) (SMD: 0·48, 95% CI 0·23, 0·72, P=0·0001), whereas co-administration of both vitamins was ineffective (vitamin C: 500-2000 mg/d; vitamin E: 400-1200 IU/d) (SMD: 0·12, 95% CI-0·18, 0·42, P=0·428). The effect of vitamin C supplementation on EF increased significantly with age (β 0·023, 95% CI 0·001, 0·05, P=0·042). There was a significant negative correlation between baseline plasma vitamin E concentration and the effect of vitamin E supplementation on EF (β-0·03, 95% CI-0·06, -0·001, P=0·029). Supplementation with either vitamin C or vitamin E alone improves EF. However, subgroup analysis emphasises the importance of careful characterisation and selection of a population group which may benefit from such supplementation.
Topics: Adenosine Triphosphate; Adult; Aged; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Dietary Supplements; Endothelium, Vascular; Female; Humans; Inflammation; Male; Middle Aged; Mitochondria; Oxidative Stress; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Regression Analysis; Vitamin E; Young Adult
PubMed: 25919436
DOI: 10.1017/S0007114515000227 -
EuroIntervention : Journal of EuroPCR... Mar 2014Cangrelor is a new antiplatelet agent that has been used in percutaneous coronary intervention (PCI) with mixed results. We aimed to review the evidence on the efficacy... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
Cangrelor is a new antiplatelet agent that has been used in percutaneous coronary intervention (PCI) with mixed results. We aimed to review the evidence on the efficacy of cangrelor in comparison to clopidogrel in reducing ischaemic endpoints at 48 hours in patients undergoing PCI in large randomised trials.
METHODS AND RESULTS
In three large clinical trials involving 25,107 participants, the risk of the primary composite efficacy endpoint of death, MI and ischaemia-driven revascularisation at 48 hours, (pooled OR 0.94; 95% CI: 0.77-1.14, p=0.51, I2=68%), death from all cause (pooled OR 0.72, 95% CI: 0.36-1.43, p=0.34, I2=52%), myocardial infarction (pooled OR 0.94, 95% CI: 0.77-1.14, p=0.51, I2=68%) was not significantly different between cangrelor and clopidogrel. Likewise, severe or life-threatening bleeding was similar between cangrelor and clopidogrel (pooled OR 1.21, 95% CI: 0.70-2.12, p=0.50, I2=0%). The risk of stent thrombosis (pooled OR 0.59, 95% CI: 0.43-0.81, p=0.001, I2=0%), Q-wave myocardial infarction (pooled OR 0.53, 95% CI: 0.30-0.92, p=0.02, I2=0%) and ischaemia-driven revascularisation (pooled OR 0.71, 95% CI: 0.52-0.98, p=0.04, I2=0%) was lower in the cangrelor group.
CONCLUSIONS
Based on this meta-analysis, we did not find any difference in the risk of the primary composite efficacy endpoint of all-cause death, ischaemia-driven revascularisation, and myocardial infarction at 48hours between cangrelor and clopidogrel use. Given that cangrelor was associated with a lower risk of stent thrombosis, ischaemia-driven revascularisation and Q-wave myocardial infarction compared to clopidogrel, cangrelor can be considered as a suitable alternative during PCI.
Topics: Adenosine Monophosphate; Clopidogrel; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stents; Thrombosis; Ticlopidine
PubMed: 24080586
DOI: 10.4244/EIJV9I11A226 -
BMJ Open Jun 2021Evaluation of remdesivir, an RNA polymerase inhibitor, for effectiveness in adults with COVID-19. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Evaluation of remdesivir, an RNA polymerase inhibitor, for effectiveness in adults with COVID-19.
DATA SOURCES
Electronic search for eligible articles of PubMed, Cochrane Central and clinicaltrials.gov was performed on 20 September 2020.
PARTICIPANTS AND STUDY ELIGIBILITY CRITERIA
Only randomised controlled trials (RCTs) evaluating efficacy of remdesivir in COVID-19 were included for meta-analysis.
INTERVENTIONS
Remdesivir was compared with standard of care.
PRIMARY AND SECONDARY OUTCOMES
Primary outcome was mortality and secondary outcomes were time to clinical improvement and safety outcomes like serious adverse events, respiratory failure.
STUDY APPRAISAL AND SYNTHESIS METHODS
Data synthesis was done with Cochrane review manager 5 (RevMan) V.5.3. Cochrane risk of bias V.2.0 tool was used for methodological quality assessment. The GRADE pro GDT was applied for overall quality of evidence.
RESULTS
52 RCTs were screened and 4 studies were included in analysis, with total of 7324 patients. No mortality benefit was observed with remdesivir versus control group (OR=0.92 (95% CI 0.79 to 1.07), p=0.30, moderate quality evidence). Significantly higher rates of clinical improvement (OR=1.52 (95% CI 1.24 to 1.87), p<0.0001, low quality) and faster time to clinical improvement (HR=1.28 (95% CI 1.12 to 1.46), p=0.0002, very low quality) was observed with remdesivir versus control group. Significant decrease was found in the risk of serious adverse events (RR=0.75 (95% CI 0.62 to 0.90), p=0.0003, low quality); however, no difference was found in the risk of respiratory failure (RR=0.85 (95% CI 0.41 to 1.77), p=0.67, very low quality evidence) with remdesivir.
CONCLUSIONS
As per the evidence from current review, remdesivir has shown no mortality benefit (moderate quality evidence) in the treatment of COVID-19. From a cost-benefit perspective, it is our personal opinion that it should not be recommended for use, especially in low and lower middle income countries.
TRIAL REGISTRATION NUMBER
PROSPERO registration number: CRD42020189517.
Topics: Adenosine Monophosphate; Adult; Alanine; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34168031
DOI: 10.1136/bmjopen-2020-048416 -
Annals of Internal Medicine May 2022Remdesivir is approved for the treatment of adults hospitalized with COVID-19. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Remdesivir is approved for the treatment of adults hospitalized with COVID-19.
PURPOSE
To update a living review of remdesivir for adults with COVID-19.
DATA SOURCES
Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021.
STUDY SELECTION
English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19.
DATA EXTRACTION
One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used.
DATA SYNTHESIS
Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event.
LIMITATION
The RCTs differed in definitions of COVID-19 severity and outcomes reported.
CONCLUSION
In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event.
PRIMARY FUNDING SOURCE
U.S. Department of Veterans Affairs.
Topics: Adenosine Monophosphate; Adult; Alanine; Humans; Physicians; United States; COVID-19 Drug Treatment
PubMed: 35226522
DOI: 10.7326/M21-4784 -
Life Sciences Jan 2021COVID-19 outbreak has created a public health catastrophe all over the world. Here, we have aimed to conduct a systematic review and meta-analysis on remdesivir use for... (Meta-Analysis)
Meta-Analysis
AIMS
COVID-19 outbreak has created a public health catastrophe all over the world. Here, we have aimed to conduct a systematic review and meta-analysis on remdesivir use for COVID-19.
MAIN METHODS
We searched Pubmed, Scopus, Embase, and preprint sites and identified ten studies for qualitative and four studies for quantitative analysis using PRISMA guidelines. The quantitative synthesis was performed using fixed and random effect models in RevMan 5.4. Heterogeneity was assessed using the I-squared (I) test.
KEY FINDINGS
Comparing 10-day remdesivir group with placebo or standard of care (SOC) group, remdesivir reduced 14 days mortality (OR 0.61, CI 0.41-0.91), need for mechanical ventilation (OR 0.73, CI 0.54-0.97), and severe adverse effects (OR 0.69, 95% CI 0.54 to 0.88). Clinical improvement on day 28 (OR 1.59, CI 1.06-2.39), day 14 clinical recovery (OR 1.48, CI 1.19-1.84), and day 14 discharge rate (OR 1.41, CI 1.15-1.73) were better among remdesivir group. Earlier clinical improvement (MD -2.51, CI -4.16 to -0.85); and clinical recovery (MD -4.69, CI -5.11 to -4.28) were seen among the remdesivir group. Longer course (10 days) of remdesivir showed a higher discharge rate at day 14 (OR 2.11, CI 1.50-2.97), but there were significantly higher rates of serious adverse effects, and drug discontinuation than the 5-day course.
SIGNIFICANCE
Remdesivir showed a better 14 days mortality profile, clinical recovery, and discharge rate. Overall clinical improvement and clinical recovery were earlier among the remdesivir group. 10-day remdesivir showed more adverse outcome than 5-day course with no significant benefits.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33121991
DOI: 10.1016/j.lfs.2020.118663 -
International Journal of Molecular... Feb 2023Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML)... (Meta-Analysis)
Meta-Analysis
Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML) patients. Imatinib is a substrate of the drug transporters ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) that can affect its plasma concentration. In the present study, the association between three genetic polymorphisms in (rs1045642, rs2032582, rs1128503) and one in (rs2231142) and the imatinib plasma trough concentration (C) was investigated in 33 GIST patients enrolled in a prospective clinical trial. The results of the study were meta-analyzed with those of other seven studies (including a total of 649 patients) selected from the literature through a systematic review process. The c.421C>A genotype demonstrated, in our cohort of patients, a borderline association with imatinib plasma trough levels that became significant in the meta-analysis. Specifically, homozygous carriers of the c.421 A allele showed higher imatinib plasma C with respect to the CC/CA carriers (C, 1463.2 ng/mL AA, vs. 1196.6 ng/mL CC + AC, = 0.04) in 293 patients eligible for the evaluation of this polymorphism in the meta-analysis. The results remained significant under the additive model. No significant association could be described between polymorphisms and imatinib C, neither in our cohort nor in the meta-analysis. In conclusion, our results and the available literature studies sustain an association between c.421C>A and imatinib plasma C in GIST and CML patients.
Topics: Humans; Adenosine Triphosphate; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Gastrointestinal Stromal Tumors; Genotype; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prospective Studies
PubMed: 36834713
DOI: 10.3390/ijms24043303 -
Journal of Human Nutrition and... Jun 2017Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of... (Review)
Review
BACKGROUND
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME.
METHODS
Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing).
RESULTS
Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10.
CONCLUSIONS
This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations.
Topics: Diet; Dietary Supplements; Exercise; Fatigue Syndrome, Chronic; Humans; NAD; Patient Outcome Assessment; Polyphenols; Probiotics; Quality of Life; Randomized Controlled Trials as Topic; Ubiquinone
PubMed: 28111818
DOI: 10.1111/jhn.12435 -
PLoS Medicine Dec 2020Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective.
METHODS AND FINDINGS
We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527).
CONCLUSIONS
In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Azithromycin; COVID-19; Critical Illness; Hospitalization; Humans; Hydroxychloroquine; Immunization, Passive; Network Meta-Analysis; Observational Studies as Topic; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 33378357
DOI: 10.1371/journal.pmed.1003501