The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
Open medicine (Warsaw, Poland). 2022;17(1):857-862
The aim of this study is to determine whether the use of tranexamic acid (TXA) in patients with hip fracture reduces intraoperative and postoperative blood loss, and on the other hand, whether it increases thromboembolic risk. The study was performed on patients with hip fracture for a period of one year. Patients were divided into two groups (1:1): the first group receiving TXA and the second group receiving placebo. The amount of blood aspiration during the surgery was measured as well as drainage in the postoperative period of 24 h. The occurrence of deep vein thrombosis (DVT) was monitored before and after the surgery by ultrasound of the lower extremities. The amount of total blood loss was two times lower in patients who received TXA (291.8 ± 65.5 mL of blood vs 634.7 ± 150.5 mL of blood). Among the patients who developed DVT, one patient was from the group that did not receive TXA, and two patients were from the group that received TXA. The use of TXA in patients with hip fracture significantly reduces intraoperative and postoperative blood loss, without a significant thromboembolic risk.
Comparing the effect of administering gelatin- low dose albumin versus albumin on renal function in liver transplantation: A randomized clinical trial
Clinical transplantation. 2022;:e14791
BACKGROUND Acute kidney injury is a common complication after liver transplantation that is independently associated with an increased risk of morbidity and mortality. This study aimed to evaluate the effects of administering gelatin-low dose albumin versus albumin on renal function and other early outcomes in liver transplantation. METHODS This randomized controlled clinical trial was conducted on 140 patients undergoing liver transplantation from brain death donors. Patients were randomly assigned to two groups: albumin or modified gelatin with albumin. Blood samples were collected before (T0) and on the first (T1), second (T2), third (T3), fifth (T4), and last day of hospitalization (T5) after liver transplantation for the detection of laboratory parameters, including renal and liver function tests. RESULTS The incidence of acute kidney injury on the basis of RIFLE criteria was 31.42 % in the gelatin group (R: 59.10 %, I: 36.40 %, and F: 4.50 %) and 25.71 % in the albumin group (R: 66.70 %, I: 27.80 %, and F: 5.50 %) (P = 0.845). Two patients in the gelatin and one in the albumin groups required renal replacement therapy. There was no significant difference between groups when the trends of changes in renal and liver function parameters were assessed during the study period (T0-T5). Furthermore, the incidence of complications was similar across groups. CONCLUSION This study showed that modified gelatin could be used without inappropriate outcomes on renal function in patients with normal preoperative kidney function tests undergoing liver transplantation. This article is protected by copyright. All rights reserved.
Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic-guided dosing of replacement therapy in haemophilia A?
Haemophilia : the official journal of the World Federation of Hemophilia. 2022
BACKGROUND To account for interindividual variability in the pharmacokinetics (PK) of factor concentrates, PK-guided dosing is increasingly implemented in haemophilia patients. Calculations are based on provided label potency, but legislation allows a potency difference of ±20% between label and actual potency. It is unknown if these differences affect PK guidance. AIM: Explore the effects of potency differences on individual factor VIII (FVIII) PK parameters and the prediction of FVIII trough levels of dosing regimens. METHODS We analyzed individual preoperative PK profiling data from severe and moderate haemophilia A patients included in the OPTI-CLOT randomized controlled trial. Label and actual potency were compared, with data on potency provided by pharmaceutical companies. For both potencies, individual PK parameters were estimated and concentration-time curves were constructed by nonlinear mixed-effects modelling. Finally, we explored the effect of both the identified and the maximum legislated potency difference on predicted FVIII trough levels infused in a low and high dose regimen. RESULTS In 45/50 included patients, actual potency was higher than its label potency. The median potency difference was 6.0% (range -9.2% to 18.4%) and resulted in varying individual PK parameter estimates but practically identical FVIII concentration-time curves. As expected, predicted FVIII trough levels were linearly correlated to the actual dose. CONCLUSION It is not necessary to take potency differences into account when applying PK guidance of FVIII concentrates in haemophilia A patients. However, when the patient is switched to another FVIII batch after PK-guided dosing, trough levels may deviate ±20% from calculations based on label dose.
Efficacy and safety of intravenous immunoglobulin in patients with lupus nephritis: A systematic review of the literature
Autoimmunity reviews. 2022;:103182
INTRODUCTION AND OBJECTIVE Intravenous immunoglobulin (IVIg) is an anti-inflammatory drug with an unclear role in the treatment of patients with lupus nephritis (LN). This systematic review evaluates the evidence for IVIg in the care of patients with LN. METHODOLOGY A systematic search was done in the PubMed, EMBASE, BVS and OVID databases - All EBM Reviews following the PRISMA methodology (registration in PROSPERO CRD42021236662). The variables were extracted: indications for use, dosage, partial or complete response, adverse reactions, initiation of renal replacement therapy, reduction of proteinuria, and mortality. The quality assessment was done with the "The Joanna Briggs Institute (JBI) Critical Appraisal tools for use in Systematic Reviews Checklist". In addition, synthesis reports were prepared through the Synthesis Without Meta-analysis - SWiM guide. RESULTS A total of 2328 articles were obtained (28 were considered for inclusion). When the studies were evaluated, IVIg therapy was found to be between 60% to 70% effective (except for patients with class V LN) with overall responses (complete + partial) even for patients who are refractory to first line treatment. Normalization (<0.5 g) of nephrotic proteinuria occurred in 24% of cases with infrequent adverse events and a mortality plus dialysis composite of 11.5% and 24.1% (most representative study). CONCLUSION In patients with LN refractory to conventional treatment or co-infection situations, the reported data seem to demonstrate effectiveness of IVIg therapy. There are few adverse reactions and caution is exercised when using it on patients with class V NL. However, given the lack of controlled studies with long-term follow-up, these data should be interpreted cautiously thus encouraging the development of high-quality RCTs.
Patients with lupus nephritis (LN), (28 studies).
Systematic review to evaluate the efficacy and safety of intravenous immunoglobulin (IVIg).
Various comparisons, including: indications for use, and dosage.
When the studies were evaluated, IVIg therapy was found to be between 60% to 70% effective (except for patients with class V LN) with overall responses (complete + partial) even for patients who were refractory to first line treatment. Normalization (<0.5 g) of nephrotic proteinuria occurred in 24% of cases with infrequent adverse events and a mortality plus dialysis composite of 11.5% and 24.1% (most representative study).
Impact of cardiopulmonary bypass duration on efficacy of fibrinogen replacement with cryoprecipitate compared with fibrinogen concentrate: a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) randomised controlled trial
British journal of anaesthesia. 2022
BACKGROUND Coagulopathy in cardiac surgery is frequently associated with acquired hypofibrinogenaemia, which can be treated with either purified fibrinogen concentrate (FC) or cryoprecipitate. Because the latter is not purified and therefore contains additional coagulation factors, it is thought to be more effective for treatment of coagulopathy that occurs after prolonged cardiopulmonary bypass (CPB). We examined the impact of CPB duration on the efficacy of the two therapies in cardiac surgery. METHODS This was a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) RCT comparing FC (4 g) to cryoprecipitate (10 U) in adult patients undergoing cardiac surgery and experiencing bleeding with acquired hypofibrinogenaemia (n=735). The primary outcome was allogeneic blood products transfused within 24 h after CPB. Subjects were stratified by CPB duration (≤120, 121-180, and >180 min). The interaction of treatment assignment with CPB duration was tested. RESULTS Subjects with longer CPB duration experienced more bleeding and transfusion. With CPB time ≤120 min (FC, n=134; cryoprecipitate, n=146), the ratio of least-squares means between the FC and cryoprecipitate groups for total allogeneic blood products at 24 h was 0.90 (one-sided 97.5% confidence interval [CI]: 0.00-1.12); P=0.004. For subjects with CPB time 121-180 min, it was 1.00 ([one-sided 97.5% CI: 0.00-1.22]; P=0.03], and for CPB time >180 min it was 0.91 ([one-sided 97.5% CI: 0.00-1.12]; P=0.005). Results were similar for all secondary outcomes, with no interaction between treatment and CPB duration for all outcomes. CONCLUSIONS The haemostatic efficacy of FC was non-inferior to cryoprecipitate irrespective of CPB duration in cardiac surgery. CLINICAL TRIAL REGISTRATION NCT03037424.
Comparison of 3-factor versus 4-factor prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis
BMC emergency medicine. 2022;22(1):14
BACKGROUND Patients requiring emergent warfarin reversal (EWR) have been prescribed three-factor prothrombin complex concentrate (PCC3) and four-factor prothrombin complex concentrate (PCC4) to reverse the anticoagulant effects of warfarin. There is no existing systematic review and meta-analysis of studies directly comparing PCC3 and PCC4. METHODS The primary objective of this systematic review and meta-analysis was to determine the effectiveness of achieving study defined target INR goal after PCC3 or PCC4 administration. Secondary objectives were to determine the difference in safety endpoints, thromboembolic events (TE), and survival during the patients' hospital stay. Random-effects meta-analysis models were used to estimate the odds ratios (OR), and heterogeneity associated with the outcomes. The Newcastle-Ottawa Scale was used to assess study quality, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS Ten full-text manuscripts and five abstracts provided data for the primary and secondary outcomes. Patients requiring EWR had more than three times the odds of reversal to goal INR when they were given PCC4 compared to PCC3 (OR = 3.61, 95% CI: 1.97-6.60, p < 0.001). There was no meaningful clinical association or statistically significant result between PCC4 and PCC3 groups in TE (OR = 1.56, 95% CI: 0.83-2.91, p = 0.17), or survival during hospital stay (OR = 1.34, 95% CI: 0.81-2.23, p = 0.25). CONCLUSION PCC4 is more effective than PCC3 in meeting specific predefined INR goals and has similar safety profiles in patients requiring emergent reversal of the anticoagulant effects of warfarin.
Corticosteroids for the treatment of Kawasaki disease in children
The Cochrane database of systematic reviews. 2022;5:Cd011188
BACKGROUND Kawasaki disease (KD), or mucocutaneous syndrome, is the leading cause of childhood-acquired heart disease in high-income countries. There is much controversy on how best to treat children with KD and in particular who may benefit from additional treatment beyond the standard intravenous immunoglobulin (IVIG) and aspirin, such as the addition of corticosteroids. This is an update of the review first published in 2017. OBJECTIVES To assess the impact of corticosteroid use on the incidence of coronary artery abnormalities in KD as either first-line or second-line treatment. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and two trials registers to 8 February 2021. We searched the reference lists of relevant articles for additional studies. SELECTION CRITERIA We selected randomised controlled trials involving children with all severities of KD who were treated with corticosteroids, including different types of corticosteroids, different durations of treatment, and where corticosteroids were used alone or in conjunction with other accepted KD treatments. We included trials using corticosteroids for both first- and second-line treatment. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, assessed study quality and extracted data using standard Cochrane methods. We performed fixed-effect model meta-analyses with odds ratios (ORs) or mean difference (MD) with 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were incidence of coronary artery abnormalities, serious adverse events, mortality, duration of acute symptoms (such as fever), time for laboratory parameters to normalise, length of hospital stay and longer-term coronary morbidity. MAIN RESULTS This update identified one new study, therefore the analysis included eight trials consisting of 1877 participants. Seven trials investigated the use of corticosteroids in first-line treatment and one investigated second-line treatment. The trials were all of good methodological quality. On pooled analysis, corticosteroid treatment reduced the subsequent occurrence of coronary artery abnormalities (OR 0.32, 95% CI 0.14 to 0.75; 8 studies, 986 participants; moderate-certainty evidence), without resultant serious adverse events (0 events; 6 studies, 737 participants; moderate-certainty) and mortality (0 events; 8 studies, 1075 participants; moderate-certainty evidence). In addition, corticosteroids reduced the duration of fever (MD -1.34 days, 95% CI -2.24 to -0.45; 3 studies, 290 participants; low-certainty evidence), time for laboratory parameters (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to normalise (MD -2.80 days, 95% CI -4.38 to -1.22; 1 study, 178 participants; moderate-certainty evidence), and length of hospital stay (MD -1.01 days, 95% CI -1.72 to -0.30; 2 studies, 119 participants; moderate-certainty evidence). None of the included studies reported long-term (greater than one year after disease onset) coronary morbidity. AUTHORS' CONCLUSIONS Moderate-certainty evidence shows that use of steroids in the acute phase of KD can be associated with reduced coronary artery abnormalities, reduced inflammatory markers and shorter duration of hospital stay when compared to no corticosteroids. There were no serious adverse events or deaths reported with or without corticosteroid use. Low-certainty evidence shows use of corticosteroids can reduce duration of clinical symptoms (fever and rash). None of the included studies reported on long-term (greater than one year after disease onset) coronary morbidity. Evidence presented in this systematic review agrees with current clinical guidelines on the use of corticosteroids in the first-line treatment in KD.
Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
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.
Comparative Efficacy of Rivaroxaban and Immunoglobulin Therapy in the Treatment of Livedoid Vasculopathy: A Systematic Review
Livedoid vasculopathy (LV) is an uncommon chronic coagulation disorder whose underlying etiology is not yet fully understood. It predominantly affects females, especially those in late adolescence. There is currently limited research on treatment options for those with this diagnosis. The present systematic review aims to compare the efficacy of rivaroxaban and intravenous immunoglobulin (IVIG) therapy in the treatment of livedoid vasculopathy. A detailed search was conducted from April 20, 2022, to May 1, 2022, using four databases: Elsevier, Medline Complete, Medline Ovid, and PubMed. Out of these, 20 relevant articles were used, and the data was extracted and analyzed. Both rivaroxaban and IVIG were shown to be effective treatment options with similar treatment response times. However, future large-scale clinical trials are needed to determine an established treatment regimen for these patients.
Multisystem Inflammatory Syndrome Temporally Related to COVID-19 in Children From Latin America and the Caribbean Region: A Systematic Review With a Meta-Analysis of Data From Regional Surveillance Systems
Frontiers in pediatrics. 2022;10:881765
BACKGROUND With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide; however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries. METHODS A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed. RESULTS Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6-7.4 years); 60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection; 59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9-10) and PICU stay 5.75 (IQR, 5-6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%. CONCLUSION Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region.