Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, et al
European journal of pediatrics. 2022;:1-12
The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, et al
Journal of hematology & oncology. 2021;14(1):37
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
Two Doses of Tranexamic Acid Reduce Blood Loss in Primary Posterior Lumbar Fusion Surgery: A Randomized-controlled Trial
Zhu X, Shi Q, Li D, Wu J, Guo K, Zheng X, Li H
Clin Spine Surg. 2020
PURPOSE Tranexamic acid (TXA) has been widely used in hip and knee arthroplasty to reduce perioperative blood loss and blood transfusion, but the dosage and efficacy of TXA in posterior lumbar spinal surgery are not fully clear. The aim of this study was to investigate the efficacy and safety of TXA and to determine whether 2 doses of TXA could reduce the blood loss in primary single-segment or double-segment posterior lumbar fusion surgery. MATERIALS AND METHODS A total of 150 patients with lumbar degenerative disease undergoing posterior lumbar interbody fusion surgery between October 2017 and February 2019 were randomized to 3 groups. Group A was treated with 0.9% normal saline solution without TXA, group B was treated with a 15 mg/kg loading dose intravenous infusion 30 minutes before surgery, and group C was treated with a 15 mg/kg loading dose intravenous infusion 30 minutes before surgery; then, the same dose was administered again 3 hours later. The assessed outcomes were the operation time, the total blood loss, the hidden blood loss, postoperative drainage, blood transfusions, incidence of venous thromboembolism, and incision infection. RESULTS The total blood loss, the hidden blood loss, and postoperative drainage were the lowest in group C. The amount of intraoperative blood loss was similar among the 3 groups. The hemoglobin and hematocrit values of the third postoperative day were the highest in group C. No significant differences in the incidence of complications and adverse events from TXA use were observed among the 3 groups. The use of TXA, the operation time, and the number of fusion segments were identified as risk factors related to total blood loss. CONCLUSION Two doses of TXA significantly reduced the total blood loss, the hidden blood loss and postoperative drainage, and decreased hemoglobin and hematocrit drop in patients undergoing posterior lumbar fusion without increasing the risk of complications.
[Clinical study on the control of intra-articular hemorrhage by tranexamic acid after shoulder arthroscopy]
Gao HL, Zhang JC, He Y, Zhai WT, Xiao LB, Shi Q
Zhongguo Gu Shang. 2020;33(3):238-41
OBJECTIVE To explore clinical effects of tranexamic acid on postoperative intra-articular hemorrhage after shoulder arthroscopy. METHODS From February to July 2018, 60 patients with rotator cuff tears treated by shoulder arthroscopy were randomly divided into observation group and control group, 30 cases in each group. In observation group, there were 6 males and 24 females; aged from 55 to 70 years old with an average age of (62.3+/-5.5) years; the courses of disease ranged from 2 to 36 months with an average of (11.7+/-1.7) months; received 0.5 g tranexamic acid (1 g of tranexamic acid was diluted with normal saline to 20 ml) in each articular cavity and subacromial space after operation. In control group, there were 5 males and 25 females; aged from 56 to 72 years old with an average of (63.4+/-5.8) years old; the courses of disease ranged from 4 to 36 months with an average of (10.8+/-1.4) months; 10 ml of normal saline was injected into joint cavity and subacromial space. Hemoglobin values between two groups before and after operation at 1 day were recorded, circumference of shoulder joint was measured preoperatively and the 1st and 7th days after operation, and circumference difference of shoulder joint was recorded. Complications such as subcutaneous blood stasis and DVT were recorded. RESULTS There was no significant difference in hemoglobin values between two groups before and after operation at 1 day (P>0.05) . On the first day after surgery, peripheral diameter of shoulder joint in observation group [(32.9+/-0.3) cm ] was significantly lower than that in control group [(35.1+/-0.5) cm ], and the circumference difference of shoulder joint in observation group [(8.7+/-0.4) mm ] was also significantly lower than that in control group [(12.3+/-0.5) mm ], the difference was statistically significant (P<0.05) . However, there was no significant difference in circumference of shoulder joint and the difference in circumference of shoulder joint between two groups on the 7th day after operation (P>0.05) . Two patients in observation group occurred subcutaneous ecchymosis, while 6 patients occurred in control group, but without statistical difference between two groups (P>0.05) . CONCLUSION Subacromial and articular injection of tranexamic acid could significantly reduce early swelling of soft tissue after arthroscopic shoulder surgery, and it has better safety.
Intravenous iron sucrose versus oral iron in the treatment of pregnancy with iron deficiency anaemia: a systematic review
Shi Q, Leng W, Wazir R, Li J, Yao Q, Mi C, Yang J, Xing A
Gynecologic & Obstetric Investigation. 2015;80((3)):170-8.
BACKGROUND Intravenous iron sucrose and oral iron therapy are the main therapies for iron deficiency anaemia (IDA), but there is still a debate regarding their efficacy and especially as to which one is the best choice during pregnancy. METHODS A meta-analysis of randomised controlled trials comparing patients treated with intravenous iron sucrose (intravenous group) with those treated with oral iron (oral group) for IDA during pregnancy was performed. The primary outcomes of interest were mean maternal haemoglobin and serum ferritin levels at the end of treatment. Secondary outcomes were treatment-related adverse events and foetal birth weight. RESULTS Six randomised controlled trials, involving a total of 576 women, were included in the present review. Significant increases in haemoglobin [mean difference (MD), 0.85; 95% confidence interval (CI), 0.31-1.39; p = 0.002] and ferritin levels (MD, 63.32; 95% CI, 39.46-87.18; p < 0.00001) were observed in the intravenous group. Compared with the oral group, there were fewer adverse events in the intravenous group (risk ratio, 0.50; 95% CI, 0.34-0.73; p = 0.0003). There was no significant difference in birth weight between the two groups. CONCLUSION For pregnant women who could not tolerate the side effects of oral treatment or required a rapid replacement of iron stores, intravenous iron sucrose was associated with fewer adverse events and was more effective than regular oral iron therapy.Copyright © 2015 S. Karger AG, Basel.