Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis
Frontiers in pharmacology. 2022;13:746265
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.
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).
Various doses of daprodustat.
Recombinant human erythropoietin (rhEPO).
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.
Comparisons of Ultrasound-Guided Platelet-Rich Plasma Intra-Articular Injection and Extracorporeal Shock Wave Therapy in Treating ARCO I-III Symptomatic Non-Traumatic Femoral Head Necrosis: A Randomized Controlled Clinical Trial
Journal of pain research. 2022;15:341-354
BACKGROUND AND OBJECTIVE Osteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients. METHODS A total of 60 patients aged 40-79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the "group by time" interaction effects. RESULTS There were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P<0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = -0.82, 95% CI [-1.39, -0.25], P=0.005), WOMAC (mean difference = -4.19, 95% CI [-7.00, -1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported. CONCLUSION This study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.
Efficacy and safety of double-filtration plasmapheresis treatment of myasthenia gravis: A systematic review and meta-analysis
OBJECTIVES To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.
The therapeutic value of arthroscopic microfracture technique in combination with platelet-rich plasma injection for knee cartilage injury
American journal of translational research. 2021;13(4):2694-2701
OBJECTIVE The purpose of this study was to analyze the efficacy of platelet-rich plasma (PRP) injection combined with arthroscopic microfracture technique for knee cartilage injury. METHODS Seventy-nine patients with knee cartilage injury were randomly divided into a control group (CG, n=39) and an observation group (OBG, n=40). Both of the groups were treated with the arthroscopic microfracture technique, and the OBG was additionally treated with PRP injection. RESULTS The VAS scores for pain in the affected area of the OBG were lower than those of the CG at 1, 3, 5, and 7 days after surgery (P < 0.05). Knee flexion, hyperextension, and rotation angles in the OBG were greater than those in the CG at 1 month after surgery (P < 0.05). IKDC scores in the OBG were lower than those in the CG at 1, 2, and 3 weeks after surgery (P < 0.05). The Tegner and Lysholm scores in the OBG were higher than those in the CG at 1, 2, and 3 months after surgery (P < 0.05). The complication rate in the OBG was 10.00%, which was lower than that of 28.21% in the CG (P < 0.05). CONCLUSION The efficacy of microfracture technique combined with PRP injection in the treatment of knee joint cartilage injury is significantly improved compared with that of microfracture technique alone, which can reduce postoperative complications and improve the range of motion and function of the knee joint.
Tranexamic Acid in Craniomaxillofacial Surgery: A Meta-Analysis and Systematic Review
Facial plastic surgery & aesthetic medicine. 2021
Objective: To compare the effectiveness of tranexamic acid (TXA) in reducing blood loss and decreasing surgery duration in craniomaxillofacial surgery. Methods: The literature was searched systematically for all comparative studies of the effect of TXA on craniomaxillofacial surgery with placebo to evaluate the efficacy of TXA in craniomaxillofacial surgery. The primary outcome was intraoperative blood loss, and secondary outcomes were postoperative hematocrit, postoperative hemoglobin, and operation duration. Results: This systematic review included 16 studies consisting of 958 patients. Meta-analysis revealed that compared with the placebo group, the TXA group showed a significant reduction in intraoperative blood loss of 139.81 mL (95% confidence interval, CI: -179.66 to -99.96 mL; p < 0.01), a shortening of the maxillary surgery duration of 15.48 min (95% CI: -21.03 to -9.92 min; p < 0.01), an elevation of the postoperative hemoglobin level of 0.74 mg/dL (95% CI: 0.42 to 1.07 mg/dL; p < 0.01), and a limited effect on increasing the postoperative hematocrit level of 1.77% (95% CI: 0.17 to 3.36; p = 0.03). Conclusion: The use of TXA in craniomaxillofacial surgery can effectively reduce intraoperative blood loss, maintain elevate postoperative hemoglobin and hematocrit levels, and reduce the operation duration.
Prophylactic transcatheter arterial embolization for high-risk ulcers following endoscopic hemostasis: a meta-analysis
World journal of emergency surgery : WJES. 2021;16(1):29
BACKGROUND To conduct a meta-analysis to assess the safety and efficacy of prophylactic transcatheter arterial embolization (PTAE) for the treatment of high-risk bleeding peptic ulcers after achieving endoscopic hemostasis. METHODS PubMed and Cochrane Library were queried for full-text articles published up to December 2019. The following keywords were used: "prophylactic embolization", "supplement embolization", "gastrointestinal bleeding", and "ulcer bleeding". High-risk ulcers were defined based on endoscopic findings (i.e., large ulcers, Forrest class I-IIb) and/or clinical presentation (i.e., hypotension, decreased hemoglobin during endoscopy). Only comparative studies investigating PTAE versus conservative treatment after achieving endoscopic hemostasis were included. Baseline study characteristics, rebleeding rate, need for surgery, mortality, and PTAE-related complication rates were investigated. Quantitative analyses were performed with Stata 15.1. RESULTS Among the five included original studies, a total of 265 patients received PTAE and 617 were managed conservatively after endoscopy. The rebleeding rate (6.8% vs 14.3%, p = 0.003) and mortality (4.5% vs 8.8%, p = 0.032) of patients from the PTAE group were lower than the control group. PTAE also reduced the cumulative need for future surgical intervention (3.0% vs 14.4%, p = 0.005). The PTAE-related major and minor events were 0.75% and 14.4%, respectively. CONCLUSION PTAE had therapeutic potentials in reducing rebleeding risk, need for surgical intervention, and morality in high-risk peptic ulcers after achieving endoscopic hemostasis. The embolization-associated adverse events were minimal. Future studies should aim to increase the sample size and resources for performing endovascular interventions.
Prevalence of Venous Thromboembolic Events in COVID-19 Patients: Systematic Review and Meta-analysis
Journal of Vascular Surgery. Venous and Lymphatic Disorders. 2020
BACKGROUND Emerging clinical evidence has shown that COVID-19 patients are complicated with venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE). The prevalence of VTE in hospitalized COVID-19 patients is unclear. METHODS Eligible studies on COVID-19 were collected from PubMed, Web of Science, and Embase. Patient characteristics and information were extracted for three categories of patients: Consecutive, ICU, and non-ICU group. All PEs and DVTs were diagnosed by computed tomographic pulmonary arteriography and duplex ultrasound, respectively. A subgroup analysis of testing strategies in ICU and non-ICU patients for PE and DVT was also performed. RESULTS Forty clinical studies involving 7966 hospitalized COVID-19 patients were included. Pooled VTE prevalence was 13% in consecutive patients (95%CI: 0.05-0.24; I(2)=97%), 7% in non-ICU patients (95%CI: 0.01-0.18; I(2)=93%), and 31% in ICU patients (95%CI: 0.22-0.42; I(2)=91%). ICU patients had the highest prevalence of PE among the three groups (17%, 95%CI: 0.12-0.23, vs. 8% in consecutive patients with 95%CI: 0.04-0.13, 4% in non-ICU with 95%CI: 0.01-0.08). ICU patients also had the highest DVT prevalence (25%, 95%CI: 0.14-0.37, vs. 7% in consecutive patients with 95%CI: 0.03-0.14, 7% in non-ICU with 95%CI: 0.02-0.14). The subgroup analysis showed a 3-fold improvement in PE and DVT detections rate in both ICU and non-ICU patients with COVID-19 when screening test for VTE was applied. In the settings of screening tests for VTE, ICU patients have a significantly higher prevalence of PE (37% vs. 10%, p<0.0001) and DVT (40% vs. 12%, p=0.0065) compared to non-ICU patients. CONCLUSIONS VTE is common in hospitalized COVID-19 patients, especially among ICU patients. Screening tests for PE and DVT may significantly improve detection rates in both ICU and non-ICU patients with COVID-19 than tests based on clinical suspicion.
Balanced crystalloids versus normal saline for fluid resuscitation in critically ill patients: A systematic review and meta-analysis with trial sequential analysis
The American journal of emergency medicine. 2019
INTRODUCTION Fluid resuscitation is a fundamental component of the management of critically ill patients, but whether choice of crystalloid affects patient outcomes remains controversial. Therefore, we performed this meta-analysis to compare the efficacy and safety of balanced crystalloids with normal saline. METHODS We searched the MEDLINE, Cochrane Central and EMBASE up to October 2018 to identify randomized controlled trials (RCTs) that compared balanced crystalloids versus normal saline in critically ill patients. The primary outcome was mortality. The secondary results were the incidence of acute kidney injury (AKI) and risk of receiving renal replacement therapy (RRT). Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using Revman 5.3, trial sequential analysis (TSA) 0.9 and STATA 12.0. RESULTS Nine RCTs were identified. The pooled analyses showed that there were no significant differences in mortality (relative risk (RR)=0.93, 95% confidence interval (CI)=0.86, 1.01, P=0.08), incidence of AKI (RR 0.94, 95% CI 0.88, 1.00, P=0.06) or RRT use rate (RR 0.94, 95% CI 0.69, 1.27, P=0.67) between balanced crystalloids and normal saline groups. However, TSA did not provide conclusive evidence. CONCLUSIONS Among critically ill patients receiving crystalloid fluid therapy, use of a balanced crystalloid compared with normal saline did not reduce the mortality, risk of severe AKI or RRT use rate. Further large randomized clinical trials are needed to confirm or refute this finding. TRIAL REGISTRATION A protocol of this meta-analysis has been registered on PROSPERO (registration number: CRD42018094857).
Synergistic Application of Platelet-Rich Fibrin and 1% Alendronate in Periodontal Bone Regeneration: A Meta-Analysis
BioMed research international. 2019;2019:9148183
Periodontal bone regeneration relies on coupled and cooperative bone formation and resorption. Accordingly a novel strategy on concurrent use of platelet-rich fibrin (PRF) (anabolic agent) and 1% alendronate (ALN) (anticatabolic agent) was proposed recently in regenerative periodontal treatment. It was supposed to enhance bone formation and reduce bone resorption simultaneously. However, there is a lack of evidence-based studies to answer whether this concurrent application was superior to single application until now. Besides, concerns on ALN lead to some reservation on this synergistic way. ALN may impair new bone formation and necrotize jaws. Thus, in order to compare the clinical efficacy between PRF plus 1%ALN and PRF alone on periodontal bone regeneration, we performed present systematic review and meta-analysis. Because it is the prerequisite for measuring the combined efficacy of PRF plus 1%ALN, firstly we evaluated the effectiveness of 1%ALN. Our data indicated that adjunctive 1%ALN was effective in promoting periodontal bone repair. Further, PRF plus 1%ALN showed a greater capacity for periodontal regeneration than PRF alone with statistical significance. The findings of this study revealed the promising prospects on synergistic application of bone anabolic agents (PRF) and antiresorption medications (1%ALN) in regenerative periodontal treatment.
Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials
BMJ open. 2019;9(1):e024350
OBJECTIVE This study aimed to compare the effects of intravenous, topical and combined routes of tranexamic acid (TXA) administration on blood loss and transfusion requirements in patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). DESIGN This was a meta-analysis of randomised controlled trials (RCT) wherein the weighted mean difference (WMD) and relative risk (RR) were used for data synthesis applied in the random effects model. Stratified analyses based on the surgery type, region, intravenous and topical TXA dose and transfusion protocol were also conducted. The main outcomes included intraoperative and total blood loss volume, transfusion rate, low postoperative haemoglobin (Hb) level and postoperative Hb decline. However, the secondary outcomes included length of hospital stay (LOS) and/or occurrence of venous thromboembolism (VTE). SETTING We searched the PubMed, Embase and Cochrane CENTRAL databases for RCTs that compared different routes of TXA administration. PARTICIPANTS Patients undergoing TKA or THA. INTERVENTIONS Intravenous, topical or combined intravenous and topical TXA. RESULTS Twenty-six RCTs were selected, and the intravenous route did not differ substantially from the topical route with respect to the total blood loss volume (WMD=30.92, p=0.31), drain blood loss (WMD=-34.53, p=0.50), postoperative Hb levels (WMD=-0.01, p=0.96), Hb decline (WMD=-0.39, p=0.08), LOS (WMD=0.15, p=0.38), transfusion rate (RR=1.08, p=0.75) and VTE occurrence (RR=1.89, p=0.15). Compared with the combined-delivery group, the single-route group had significantly increased total blood loss volume (WMD=198.07, p<0.05), greater Hb decline (WMD=0.56, p<0.05) and higher transfusion rates (RR=2.51, p<0.05). However, no significant difference was noted in the drain blood loss, postoperative Hb levels and VTE events between the two groups. The intravenous and topical routes had comparable efficacy and safety profiles. CONCLUSIONS The combination of intravenous and topical TXA was relatively more effective in controlling bleeding without increased risk of VTE.