Abstract

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.

Abstract

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO) versus HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs. 66.7%, P < 0.001) and complete response (CR, 75.0% vs. 42.7%, P < 0.001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs. 36.5%, P = 0.02; sustained CR: 46.0% vs. 32.3%, P = 0.043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = 0.04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044. This article is protected by copyright. All rights reserved.

Abstract

OBJECTIVE We performed a systematic review and meta-analysis to evaluate the efficacy and safety of therapeutic plasma exchange (TPE) in adult patients with autoimmune hemolytic anemia (AIHA). METHODS A search of major English and Chinese databases for randomized controlled trials (RCTs) comparing the use of TPE against no TPE in adult AIHA patients was performed. Outcomes were remission incidence, hematological parameters (ie, hemoglobin count, red blood cell count, reticulocyte percentage, total bilirubin, and hematocrit) and adverse event incidence. RESULTS Thirteen RCTs containing 906 patients were included. A majority of RCTs were given an unclear risk of bias. TPE was associated with increased remission incidence (risk ratio [RR] = 1.22, 95% confidence interval [CI] = 1.15-1.30) and improved hematological parameters. TPE was also associated with an insignificant increase in adverse event incidence (RR = 1.12, 95% CI = 0.68 to 1.86). Publication bias was detected for remission incidence and reticulocyte percentage, and it may have led to an overestimation of beneficial improvements in reticulocyte percentage. CONCLUSION TPE was associated with both increased remission incidence and improved hematological parameters. It is capable of improving short-term hematological parameters to stabilize acute AIHA onset. Our results should be interpreted with caution due to the unclear risk of bias and the presence of publication biases. We were not able to determine the treatment effects for cold and warm AIHA separately due to a lack of subgroup data. Future RCTs incorporating larger sample sizes with subgroup data for warm and cold AIHA are needed to validate our findings and establish subgroup efficacy and safety.

Abstract

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).

Abstract

Objective: The aim of this study was to compare the effectiveness of different fluids on critically ill patients who need fluid resuscitation through a systematic review and network meta-analysis (NMA). Data sources: Electronic databases were searched up to March 2018 for randomized controlled trials comparing the effectiveness of different fluids in critically ill patients. The primary outcome was mortality, and the secondary outcomes were the incident of acute kidney injury (AKI) and risk of receiving renal replacement therapy (RRT). A Bayesian NMA was conducted, and the quality of evidence contributing to each network estimate was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria. Results: We deemed 49 trials eligible, including 40,910 participants. The quality of evidence was rated as moderate in most comparisons. There was no significant difference among resuscitation fluids in mortality. NMA at the 9-node level showed the most effective fluid was balanced crystalloid (BC) (80.79%, the ranking of resuscitation fluid based on cumulative probability plots and surface under the cumulative ranking curves [SUCRAs]). NMA at the 10-node level showed that the most effective fluid was Plasma-Lyte (77.52%). Results of sensitivity analyses in mortality did not reveal any significant changes in the findings for primary outcomes. High-molecular-weight hetastarch (H-HES) was associated with an increased incidence of AKI when compared with gelatin (odds ratio [OR], 0.43; 95% credibility interval [CrI], 0.19-0.94), low-molecular-weight hetastarch (L-HES; OR, 0.50; 95% CrI, 0.30-0.87), BC (OR, 0.55; 95% CrI, 0.34-0.88), and normal saline (OR, 0.56; 95% CrI, 0.34-0.93). Meanwhile, H-HES was also associated with an increased risk of receiving RRT when compared with BC (OR, 0.51; 95% CrI, 0.27-0.93) and normal saline (OR, 0.52; 95% CrI, 0.24-0.96). Conclusion: BCs, especially the Plasma-Lyte, are presumably the best choice for most critically ill patients who need fluid resuscitation. Meanwhile, the use of H-HES was associated with an increased incidence of AKI and risk of receiving RRT. Registration: PROSPERO (CRD42017072728).