Abstract

WHAT IS KNOWN AND OBJECTIVE This study was performed to compare the efficacy and safety of combined administration of intravenous (IV) and intra-articular (IA) tranexamic acid (TXA) with IV or IA TXA alone in total knee arthroplasty (TKA). METHODS PubMed, Embase, Cochrane Library and Web of Science were searched for randomized controlled trials (RCTs) in July 2021. Total blood loss, transfusion rate, postoperative haemoglobin drop, drain output, deep venous thrombosis (DVT) and pulmonary embolism (PE) were pooled. Data were analyzed using Stata 14.0 software. The study protocol was registered with PROSPERO, number CRD42020186654. RESULTS Ten RCTs involving 1306 patients were included. Combined TXA group provided lower total blood loss (SMD -0.47; 95% CI -0.64 to -0.30; p < 0.001), postoperative haemoglobin drop (SMD -0.47; 95% CI -0.60 to -0.33; p < 0.001) and drain output (SMD -0.50; 95% CI -0.71 to -0.29; p = 0.009) compared with IV or IA TXA alone group. No significant difference was found in terms of transfusion rate (OR 0.53; 95% CI 0.23 to 1.23; p = 0.137) and DVT (OR 0.55; 95% CI 0.18 to 1.68; p = 0.293). PE data was provided by all 10 studies, but PE only occurred in one patient in IV TXA alone group. WHAT IS NEW AND CONCLUSION Combined administration of IV and IA TXA was relatively more effective in reducing total blood loss, transfusion rate, postoperative haemoglobin drop, and drain output after TKA. TXA may not increase the risk of DVT/PE, but it also needs to be monitored in clinical application.

Abstract

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Abstract

RATIONALE Iron deficiency, in the absence of anaemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin levels. The safety and benefit of parenteral iron replacement in this patient population is unclear. OBJECTIVES To evaluate the safety and efficacy of parenteral iron replacement in pulmonary arterial hypertension. METHODS In two randomised, double blind, placebo-controlled 12 week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject®) 1000 mg (or 15 mg/kg if weight < 66.7Kg) or saline as placebo and 17 patients in China received iron dextran (Cosmofer®) 20 mg iron/kg body weight or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by: a serum ferritin < 37 µg/l or iron < 10.3 µmol/l or transferrin saturations < 16.4%. RESULTS Both iron treatments were well tolerated and improved iron status. Analysed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6 minute walk test) or cardio-pulmonary haemodynamics, as assessed by right heart catheterisation, cardiac magnetic resonance or plasma NT-proBNP, at 12 weeks. CONCLUSION Iron repletion by administration of a slow release iron preparation as a single infusion to PAH patients with iron deficiency without overt anaemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).

Abstract

As the number of fusion levels increases, the complexity of spinal correction surgery also increases. Thus, we conducted this study to determine the safety and efficacy of tranexamic acid (TXA) involving eight or more spinal fusion levels. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines, a search of the PubMed, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov databases was conducted for relevant studies published prior to May 30, 2019. The primary outcomes, including blood loss and transfusion requirement, and the secondary outcomes, including general indices, postoperative hemoglobin, and coagulation function, were analyzed using Rev Man 5.3.5 software and STATA version 12.0. Eight randomized controlled trials (473 participants) were included in the study. Compared to the control treatments, TXA reduced intraoperative blood loss, total blood loss, transfusion volume, and prothrombin time. There were no significant differences between the TXA and non-TXA groups in transfusion rate, operative time, hospital stay, complications, hemoglobin level, and other coagulation function parameters. In the pediatric subgroup analysis, TXA additionally improved hemoglobin levels, platelet count, and prothrombin time international normalized ratio. The present meta-analysis showed that TXA reduced blood loss and transfusion volume in both adults and children. In pediatric patients, TXA led to a greater benefit in postoperative hemoglobin levels and coagulation function. Intravenous TXA is safe and effective in children with eight or more spinal corrective levels.

Abstract

Background: Total knee arthroplasty (TKA) surgery has a lot of complications, especially hemorrhage, which can be controlled via tranexamic acid (TXA). The guidelines endorse the integration of TXA interventions in the management of TKA-induced complications. However, uncertainty surrounds the effects of different TXA therapies. This frequentist model network meta-analysis (NMA) aims to compare hemorrhage control and deep venous thrombosis (DVT) rate of different TXA therapies in TKA. Methods: Articles were searched with the PubMed, Embase, Cochrane Library, and Web of Science from 1966 to October 2020. Randomized controlled trials (RCTs) comparing different TXA therapies, or with placebo in patients with TKA were included. Two investigators independently conducted article retrievals and data collection. The outcome was total blood loss and DVT rate. Effect size measures were mean differences (MDs), or odds ratios (ORs) with 95% confidence intervals (CIs). We conducted a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses were performed in Stata software or R software. The study protocol was registered with PROSPERO, number CRD42020202404. Results: We identified 1 754 citations and included 81 studies with data for 9 987 patients with TKA. Overall, all TXA therapies were superior to placebo for total blood loss in TKA. Of all TXA therapies, M therapy (IV/IV infusion + oral TXA > 3g) was most effective for total blood loss (MD=-688.48, -1084.04--328.93), followed by F therapy (IV TXA ≥ 15 mg/kg or 1 g three times). TXA therapies in this study are not associated with the increase of DVT risk. Conclusions: TXA therapies in this study are effective and safe for the treatment of TKA-induced complications. M therapy (IV/IV infusion + oral TXA > 3 g) may be the most effective TXA therapy for hemorrhage control. TXA therapies in this study do not increase DVT risk. Considering hemorrhage control and DVT rate simultaneously, F therapy (IV TXA ≥ 15 mg/kg or 1 g three times) may be suggested to apply for TKA, and this study may provide a crucial clue to future TXA use.

Abstract

BACKGROUND Catecholamines are the first-line vasopressors used in patients with septic shock. However, the search for novel drug candidates is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity. Terlipressin (TP) is a synthetic vasopressin analogue used in the management of patients with septic shock. In the current study, we aimed to compare the effects of TP and catecholamine infusion in treating septic shock patients. METHODS A systematic review and meta-analysis was conducted by searching articles published in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials between inception and July 2018. We only selected randomized controlled trials evaluating the use of TP and catecholamine in adult patients with septic shock. The primary outcome was overall mortality. The secondary outcomes were the ICU length of stay, haemodynamic changes, tissue perfusion, renal function, and adverse events. RESULTS A total of 9 studies with 850 participants were included in the analysis. Overall, no significant difference in mortality was observed between the TP and catecholamine groups (risk ratio(RR), 0.85 (0.70 to 1.03); P = 0.09). In patients < 60 years old, the mortality rate was lower in the TP group than in the catecholamine group (RR, 0.66 (0.50 to 0.86); P = 0.002). There was no significant difference in the ICU length of stay (mean difference, MD), - 0.28 days; 95% confidence interval (CI), - 1.25 to 0.69; P = 0.58). Additionally, TP improved renal function. The creatinine level was decreased in patients who received TP therapy compared to catecholamine-treated participants (standard mean difference, SMD), - 0.65; 95% CI, - 1.09 to - 0.22; P = 0.003). No significant difference was found regarding the total adverse events (Odds Ratio(OR), 1.48(0.51 to 4.24); P = 0.47), whereas peripheral ischaemia was more common in the TP group (OR, 8.65(1.48 to 50.59); P = 0.02). CONCLUSION The use of TP was associated with reduced mortality in septic shock patients less than 60 years old. TP may also improve renal function and cause more peripheral ischaemia. PROSPERO registry: CRD42016035872.

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

Abstract

INTRODUCTION Treatment effects of antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin are controversial in patients with Coronavirus disease 2019 (COVID-19). OBJECTIVES To evaluate the impact of drug therapy on the risk of death in patients with COVID-19. PATIENTS AND METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, and major preprint platforms were searched to retrieve articles till 7 April 2020. The effects of specific drug interventions on mortality were assessed in COVID-19 patients. Odds ratios (ORs) and Risk Ratios (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS Of 3421 references, six studies were included. Pooled results from retrospective studies revealed that antiviral agents may contribute to survival benefit (OR, 0.42, 95% CI, 0.17-0.99, p=0.048, I2=82.8%), while the RCT found no effects of antiviral agent on mortality (RR 0.77, 95% CI, 0.45-1.30, p=0.33). Glucocorticoids usage leads to an increased risk of death (OR 2.43, 95% CI, 1.44-4.10, p=0.001, I2=61.9%). Antibiotics intervention did not significantly affect mortality (OR 1.13, 95% CI, 0.67-1.89, p=0.64, I2=0%). Likewise, intravenous immunoglobulin had non-significant effects on mortality (OR 2.66, 95% CI, 0.72-9.89, p=0.14, I2=93.1%). CONCLUSIONS With the varied heterogeneities across interventions, the current evidence indicated a probable survival benefit of antiviral agent usage and a harmful effect of glucocorticoids in patients with COVID-19. None of antibiotics or intravenous immunoglobulin usage was associated with survival benefit in patients with COVID-19.

Abstract

BACKGROUND Patients with septic shock in whom Norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of Vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP. METHODS The PubMed, Embase and Cochrane Central Register databases were searched from the database inception until October 18, 2018. Studies were limited to adult patients with septic shock who received concomitant NE and VP treatment, that included different orders of vasopressor discontinuation. The primary outcome was the incidence of hypotension. Overall mortality, ICU mortality and length of stay in the ICU (LOS) were secondary outcomes. Sensitivity and subgroup analyses, as well as trial sequential analysis (TSA), were performed. RESULTS One prospective randomized controlled trial and seven retrospective cohort studies were included in present meta-analysis. Compared with discontinuing VP first, the incidence of hypotension was significantly lower when NE was discontinued first (OR 0.3, 95% CI 0.10 to 0.86, P = 0.02; I = 91%). No significant difference was detected in either overall mortality (OR 1.28, 95% CI 0.77 to 2.10, P = 0.34) or ICU mortality (OR 0.99, 95% CI 0.74 to 1.34, P = 0.96) between these two groups. Furthermore, ICU length of stay (LOS) was also evaluated in five studies, and no statistical significance was observed between the two groups with different orders in weaning vasopressors (mean difference, 1.35, 95% CI -2.05 to 4.74, P = 0.44). The subgroup analyses suggested a significant association between hypotension and the practice of discontinuing VP first specifically in patients with a low usage rate of corticosteroids (OR 0.18, 95% CI 0.04 to 0.78, P = 0.02). The TSA indicated a lack of sufficient evidence to draw conclusions from the current results (RIS = 11,821). CONCLUSIONS In adults with septic shock treated with concomitant VP and NE therapy, discontinuing VP first may lead to a higher incidence of hypotension but is not associated with mortality or ICU LOS. Further prospective studies with larger sample sizes are warranted.

Abstract

OBJECTIVE The purpose of this study was (1) to perform a summary of meta-analyses comparing platelet-rich plasma (PRP) injection with hyaluronic acid (HA) and placebo injection for KOA patients, (2) to determine which meta-analysis provides the best available evidence to making proposals for the use of PRP in the treatment of KOA patients, and (3) to highlight gaps in the literature that require future investigation. MATERIAL AND METHODS PubMed, EMBASE, and Cochrane databases search were performed for meta-analyses which compared PRP injection with HA or placebo. Clinical outcomes and adverse events were extracted from these meta-analyses. Meta-analysis quality was assessed using the Quality of Reporting of Meta-analyses (QUOROM) systems and the Oxman-Guyatt quality appraisal tool. The Jadad decision algorithm was also used to determine which meta-analysis provided the best available evidence. RESULTS Four meta-analyses were included in our study, and all of these articles were Level I evidence. The QUOROM score of each included meta-analysis range from 14 to 17 points (mean score 15, maximum score 18), and the Oxman-Guyatt score range from 4 to 6 points (mean score 5, maximum score 7). Three meta-analyses indicated PRP showed more benefit in pain relief and functional improvement than the control group, and the other one suggested no difference between these groups. All included meta-analyses found no statistical difference in adverse events between these groups. In addition, a meta-analysis conducted by Shen et al. got the highest methodological quality score and suggested that PRP provided better pain relief and function improvement in the treatment of KOA. CONCLUSIONS For short-term follow-up (≤1 year), intra-articular PRP injection is more effective in terms of pain relief and function improvement in the treatment of KOA patients than HA and placebo, and there is no difference in the risk of an adverse event between PRP and HA or placebo. LEVEL OF EVIDENCE Level I evidence, a summary of meta-analyses TRIAL REGISTRATION PROSPERO ID CRD42018116168.