1.
Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis
Fu Z, Geng X, Chi K, Song C, Wu D, Liu C, Hong Q
Frontiers in pharmacology. 2022;13:746265
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Abstract
Introduction: Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia. Methods: We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis. Results: Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = -0.01, 95% confidence interval (CI) = -0.38, 0.35, p = 0.95; MD = 0.15, 95% CI = -0.29, 0.60, p = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients (p < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, p = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, p = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result. Conclusion: Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.
PICO Summary
Population
People with chronic kidney disease (CKD) with or without dialysis, suffering from anaemia and participating in randomised controlled trials (RCTs), (n= 7,933, 7 RCTs).
Intervention
Various doses of daprodustat.
Comparison
Recombinant human erythropoietin (rhEPO).
Outcome
For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in haemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD)= -0.01, 95% confidence interval (CI)= -0.38, 0.35; MD= 0.15, 95% CI= -0.29, 0.60; respectively). In addition, a significant increase in transferrin saturation, total iron binding capacity and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients. As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR)= 0.99, 95% CI= 0.92, 1.06), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR= 1.04, 95% CI= 1.01,1.07), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result.
2.
Risk factors and mortality of pulmonary embolism in COVID-19 patients: Evidence based on fifty observational studies
Fu Z, Bai G, Song B, Wang Y, Song H, Ma M, Zhu J, Zhang Z, Kang Q
Medicine. 2022;101(45):e29895
Abstract
BACKGROUND At present, many studies have described acute pulmonary embolism (PE) as a frequent and prognostically relevant complication of coronavirus disease 2019 (COVID-19) infection. Thus we performed the present analysis of 50 studies to evaluate the risk factors and mortality of PE in COVID-19 patients. METHOD Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to October, 2021. Odds ratio (OR), mean difference (MD) or standard MD was used to evaluate the outcomes. The primary outcomes were the difference of mortality between PE and non-PE COVID-19 patients as well as relevant risk factors of PE in COVID-19 patients. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULT A total of 50 studies including 10053 patients were included in this meta-analysis. Our results indicated that COVID-19 patients with PE experienced significantly higher mortality than non-PE patients (21.9% vs. 10.7%), with a pooled OR of 2.21 (95% CI 1.30 - 3.76; P = .003). In addition, COVID-19 patients with PE also experienced more mechanical ventilation (MV) (OR 2.21; 95% CI 1.30 - 3.75; P = .003) and invasive mechanical ventilation (IMV) (OR 3.58; 95% CI 2.47 - 5.20; P < .0001) respectively. Univariate analysis (UVA) results indicated the Sequential Organ Failure Assessment (SOFA) score, time to deep venous thrombosis (DVT), nonintensive care unit (non-ICU) patients and no anticoagulation as risk factors of PE for COVID-19 patients. In addition, multivariate analysis also found that SOFA score, D-dimer, BMI > 30 kg/m2 and history of PE were risk factors of PE for COVID-19 patients. CONCLUSION The present analysis indicated that PE increased the mortality of COVID-19 patients. Mechanical ventilation, especially invasive mechanical ventilation, is correlated with an increased incidence of PE in patients with COVID-19. The incidence of PE for COVID-19 patients may be multifactorial and further researches focused on risk factors were needed in the future.
3.
Effectiveness of intravenous immunoglobulin for children with severe COVID-19: A rapid review
Zhang J, Yang Y, Yang N, Ma Y, Zhou Q, Li W, Wang X, Huang L, Luo X, Fukuoka T, et al
Annals of Translational Medicine. 2020
Abstract
Background: Intravenous immunoglobulin (IVIG) is usually used as supportive therapy, but the treatment of COVID-19 by IVIG is controversial This rapid review aims to explore the clinical effectiveness and safety of IVIG in the treatment of children with severe COVID-19 Methods: We systematically searched the literature on the use of IVIG in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), including both adults and children We assessed the risk of bias and quality of evidence and reported the main findings descriptively Results: A total of 1,519 articles were identified by initial literature search, and finally six studies met our inclusion criteria, included one randomized controlled trial (RCT), four case series and one case report involving 198 patients One case series showed the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS) was not improved by IVIG One case report showed high-dose IVIG could improve the outcome of COVID-19 adults Three observational studies showed inconsistent results of the effect of IVIG on SARS patients One RCT showed that IVIG did not reduce mortality or the incidence of nosocomial infection in adults with severe SARS The quality of evidence was between low and very low Conclusions: The existing evidence is insufficient to support the efficacy or safety of IVIG in the treatment of COVID-19