scholarly journals Exposure–Response Relationship of Tranexamic Acid in Cardiac Surgery

2020 ◽  
Author(s):  
Paul Jacques Zufferey ◽  
Julien Lanoiselée ◽  
Billal Graouch ◽  
Baptiste Vieille ◽  
Xavier Delavenne ◽  
...  
Keyword(s):  
Tranexamic Acid ◽  
Total Dose ◽  
Low Dose ◽  
Meta Analysis ◽  
Credible Interval ◽  
High Dose ◽  
Response Relationship ◽  
Randomized Controlled ◽  
Exposure Response ◽  
Relationship Of

Background It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid–associated seizure may be dose-related. The authors’ aim was to characterize the exposure–response relationship of this drug. Methods Databases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery. Observational studies were added for seizure assessment. Tranexamic acid concentrations were predicted in each arm of each study using a population pharmacokinetic model. The exposure–response relationship was evaluated by performing a model-based meta-analysis using nonlinear mixed-effect models. Results Sixty-four randomized controlled trials and 18 observational studies (49,817 patients) were included. Seventy-three different regimens of tranexamic acid were identified, with the total dose administered ranging from 5.5 mg/kg to 20 g. The maximum effect of tranexamic acid for postoperative blood loss reduction was 40% (95% credible interval, 34 to 47%), and the EC50 was 5.6 mg/l (95% credible interval, 0.7 to 11 mg/l). Exposure values with low-dose regimens approached the 80% effective concentration, whereas with high-dose regimens, they exceeded the 90% effective concentration. The predicted cumulative blood loss up to 48 h postsurgery differed by 58 ml between the two regimens, and the absolute difference in erythrocyte transfusion rate was 2%. Compared to no tranexamic acid, low-dose and high-dose regimens increased the risk of seizure by 1.2-fold and 2-fold, respectively. However, the absolute risk increase was only clinically meaningful in the context of prolonged open-chamber surgery. Conclusions In cardiopulmonary bypass surgery, low-dose tranexamic acid seems to be an appropriate regimen for reducing bleeding outcomes. This meta-analysis has to be interpreted with caution because the results are observational and dependent on the lack of bias of the predicted tranexamic acid exposures and the quality of the included studies. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Different Dose Regimens of Intravenous Tranexamic Acid in Adolescent Spinal Deformity Surgery: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Zhencheng Xiong ◽  
Kexin Wu ◽  
Jiayu Zhang ◽  
Delong Leng ◽  
Ziyi Yu ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Spinal Deformity ◽  
Dose Group ◽  
Low Dose ◽  
Operative Time ◽  
Meta Analysis ◽  
High Dose ◽  
Spinal Deformity Surgery

Objective. To evaluate the efficacy and safety of different dose regimens of intravenous (IV) tranexamic acid (TXA) in adolescent spinal deformity surgery. Methods. Two researchers independently searched multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science to find studies that met the inclusion criteria. A meta-analysis was performed based on the guidelines of the Cochrane Reviewer’s Handbook. Results. Six randomized controlled trials (RCTs) and eleven non-RCTs were identified, including 1148 patients. According to different dose regimens of IV TXA, the included studies were divided into the high-dose group and the low-dose group. Compared with placebo, both groups had less total blood loss (TBL) (high dose: WMD = − 1737.55 , 95% CI: (-2247.16, -1227.94), P < 0.001 , I 2 = 0 % ; low dose: WMD = − 528.67 , 95% CI: (-666.06, -391.28), P < 0.001 , I 2 = 0 % ), intraoperative blood loss (IBL) (high dose: WMD = − 301.48 , 95% CI: (-524.3, -78.66), P = 0.008 , I 2 = 60.3 % ; low dose: WMD = − 751.14 , 95% CI: (-967.21, -535.08), P < 0.001 , I 2 = 0 % ), and blood transfusion rates (high dose: RR = 0.19 , 95% CI: (0.1, 0.37), P < 0.001 , I 2 = 0 % ; low dose: RR = 0.4 , 95% CI: (0.18, 0.91), P = 0.029 , I 2 = 57 % ). High-dose IV TXA use was associated with more vertebral fusion segments ( WMD = 0.53 , 95% CI: (0.23, 0.82), P < 0.001 , I 2 = 31.2 % ). Low-dose IV TXA use was associated with shorter operative time ( WMD = − 18.43 , 95% CI: (-26.68, -10.17), P < 0.001 , I 2 = 0 % ). Conclusion. High-dose and low-dose IV TXA were effective in reducing TBL, IBL, and blood transfusion rates without increasing complications in adolescent patients undergoing spinal deformity surgery. Low-dose IV TXA was effective in reducing the operative time. Both the high-dose and low-dose groups had similar preoperative and postoperative Hb levels compared to the control group.

scholarly journals Dose-Dependent Efficacy of Aripiprazole in Treating Patients With Schizophrenia or Schizoaffective Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Qian ◽  
Liao Xuemei ◽  
Li Jitao ◽  
Su Yun'Ai ◽  
Si Tianmei
Keyword(s):  
Side Effects ◽  
Dose Group ◽  
Low Dose ◽  
Meta Analysis ◽  
High Dose Group ◽  
Controlled Trials ◽  
High Dose ◽  
Randomized Controlled ◽  
Syndrome Scale ◽  
Mean Differences

Purpose: To compare the efficacy and tolerability of different administration strategies of aripiprazole.Methods: We searched MEDLINE, EMBASE, the Cochrane Central, Web of Science, China National Knowledge Infrastructure(CNKI), and Wanfang Data Knowledge Service Platform(Wanfang) for randomized controlled trials (RCTs) of aripiprazole, using the terms: (aripiprazole) AND (schizophr* OR schizoaff*) AND (“syndrome scale” OR PANSS) AND (clini* OR trial). We retrieved study design, participant characteristics, comparison groups, and outcomes from each study.Results: In total, nine RCTs were selected for meta-analysis, which covered ~1,187 participants. We defined two treatment groups that represent different treatment strategies: (1) the high-dose group (the high-dose strategy) rapidly increased to doses higher than 15 mg/day in 2 weeks or began with doses higher than 15 mg/day, otherwise the group was defined as (2) the low-dose group (the low-dose strategy). If the initial or target doses of aripiprazole in a study were all higher than 15 mg/day, the high- and low-dose groups were created based on the relative level of the dose. The high-dose group showed significantly greater reductions in Positive and Negative Syndrome Scale (PANSS) total scores (standardized mean differences = −8.31, 95% confidence interval [CI] = −16.48, −0.13; P &lt; 0.01; I2 = 96%) than the low-dose group. The high-dose group showed superior effects compared with the low-dose group in long-term studies (more than 8 weeks) (standardized mean differences = −13.81, 95% CI = −25.07, −2.55; P &lt; 0.01; I2 = 96%). With exception of somnolence, we did not find significant differences in side effects or discontinuation due to adverse events. Sensitivity analyses produced similar results.Conclusion: The high-dose treatment strategy of aripiprazole for patients with schizophrenia or schizoaffective disorder may bring more benefits without obvious side effects.

scholarly journals Efficacy and Safety of Wenxin Granules and Propafenone in Treatment of Atrial Premature Beats: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Yuan ◽  
Xing-jiang Xiong ◽  
Duo-duo Li ◽  
Hai-xia Li ◽  
Jian-ping Fu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Low Dose ◽  
Sinus Bradycardia ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
High Dose ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Premature Beats

Objective. A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs). Methods. A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used. Results. Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), P<0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), P=0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), P=0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), P=0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), P=0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval. Conclusion. Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification.

scholarly journals Effects of Vitamin D Supplementation on Cardiovascular and Glycemic Biomarkers

2021 ◽  
Author(s):  
Jennifer Miao ◽  
Katherine N. Bachmann ◽  
Shi Huang ◽  
Yan Ru Su ◽  
Jeffery Dusek ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Low Dose ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Model Assessment ◽  
Neurohormonal Activation ◽  
Randomized Controlled

Background Experimental and observational studies have suggested a link between vitamin D and cardiovascular and metabolic disease, but this has not been confirmed in randomized controlled trials. We sought to determine whether vitamin D supplementation reduces biomarkers of insulin resistance, inflammation, neurohormonal activation, and lipids. Methods and Results This was a prespecified, secondary analysis of the DAYLIGHT (Vitamin D Therapy in Individuals at High Risk of Hypertension) randomized controlled trial. We measured circulating homeostatic model assessment of insulin resistance, hs‐CRP (high‐sensitivity C‐reactive protein), N‐terminal pro‐B‐type natriuretic peptide, renin, aldosterone, and lipids at baseline and at 6 months in 289 individuals with low vitamin D status (25‐hydroxyvitamin‐D [25‐OH‐D] ≤25 ng/mL) receiving low‐dose (400 IU/d) versus high‐dose (4000 IU/d) vitamin D3 for 6 months. A meta‐analysis of randomized controlled trials reporting biomarker changes after vitamin D supplementation was then performed. Levels of 25‐OH‐D increased in the high‐dose relative to the low‐dose vitamin D group (+15.5 versus +4.6 ng/mL, P <0.001). Changes in biomarkers of glycemia, inflammation, and neurohormonal activation did not differ by dose. Lipids did not differ between groups, other than triglycerides, which increased in the high‐dose compared with the low‐dose group (+11.3 versus −6.2 mg/dL, P <0.001). The meta‐analysis showed potential modest decreases in homeostatic model assessment of insulin resistance and hs‐CRP, but no changes in low‐density lipoprotein, after vitamin D supplementation compared with control groups. Conclusions In the DAYLIGHT randomized controlled trial, high‐dose vitamin D supplementation did not improve biomarkers of glycemia, inflammation, neurohormonal activation, or lipids. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01240512.

scholarly journals Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Dose Group ◽  
Low Dose ◽  
Radioiodine Therapy ◽  
Meta Analysis ◽  
High Dose Group ◽  
High Dose ◽  
Fixed Effects Model ◽  
Recombinant Human Thyrotropin

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

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