Abstract

BACKGROUND To develop a risk prediction model for the occurrence of severe acute kidney injury (AKI) in intensive care unit (ICU) patients receiving fluid resuscitation. METHODS We conducted a secondary analysis of the Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) trial, a blinded randomized controlled trial that enrolled ICU patients who received intravenous fluid resuscitation. The primary outcome was the first event in a composite outcome of doubling of serum creatinine and/or treatment with renal replacement treatment (RRT) within 28 days of randomization. The final model developed using multivariable logistic regression with backwards elimination was validated internally and then translated into a predictive equation. RESULTS Six thousand seven hundred twenty-seven ICU participants were studied, among whom 745 developed the study outcome. The final model having six variables, including admission diagnosis of sepsis, illness severity score, mechanical ventilation, tachycardia, baseline estimated glomerular filtration rate and emergency admission. The model had good discrimination (c-statistic = 0.72, 95% confidence interval 0.697-0.736) and calibration (Hosmer-Lemeshow test, χ(2) = 14.4, p = 0.07) for the composite outcome, with a c-statistic after internal bootstrapping validation of 0.72, which revealed a low degree of over-fitting. The positive predictive value and negative predictive value were 58.8 and 89.1%, respectively. The decision curve analysis indicates a net benefit in prediction of severe AKI using the model across a range of threshold probabilities between 5 and 35%. CONCLUSIONS Our model, using readily available clinical variables to identify ICU patients at high risk of severe AKI achieved good predictive performance in a clinically relevant population.

Abstract

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.

Abstract

BACKGROUND The efficacy of tranexamic acid for subarachnoid hemorrhage remains controversial. Thus, we conduct this meta-analysis to explore the efficacy of tranexamic acid for subarachnoid hemorrhage. METHODS PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on subarachnoid hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. RESULTS Five RCTs and 2359 patients were included in the meta-analysis. Overall, compared with control intervention for subarachnoid hemorrhage, tranexamic acid was associated with significantly reduced risk of rebleeding (Odd ratio [OR] =0.62; 95% confidence interval [CI] =0.41 to 0.93; P = 0.02), but had no influence on mortality (OR = 0.94; 95% CI = 0.75 to 1.18; P = 0.61), poor outcome (OR = 0.95; 95% CI = 0.61 to 1.48; P = 0.82), hydrocephalus (OR = 1.17; 95% CI = 0.94 to 1.46; P = 0.17) or delayed cerebral ischemia (OR = 1.26; 95% CI = 0.78 to 2.04; P = 0.34). CONCLUSIONS Tranexamic acid may be effective to reduce the risk of rebleeding in patients with subarachnoid hemorrhage.

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

BACKGROUND Tranexamic acid (TXA) has been widely used during on-pump coronary artery bypass graft (CABG) surgery owing to its antifibrinolytic effect. However, the efficacy and safety of TXA in off-pump CABG surgery remains unconfirmed, especially intravenous (IV) administration. OBJECTIVE The aim of this study was to evaluate the effectiveness and safety of IV administration of TXA in off-pump CABG settings. METHODS AND RESULTS A comprehensive literature search was performed to identify randomized controlled trials (RCTs) that compared IV use of TXA with placebo in the reduction of postoperative 24-hour blood transfusion, as well as postoperative death and thrombotic events. The combined estimations were compiled with a fixed-effects model or, if heterogeneity existed, a random-effects model. Funnel plots and Egger's test were used to assess potential publication bias. Subgroup analyses were used to explore possible sources of heterogeneity. In total, 12 RCTs met the inclusion criteria. IV administration of TXA significantly reduced the risk of packed red blood cell (PRBC) transfusion [risk ratio (RR) = 0.61, 95% confidence interval (CI) 0.503 to 0.756, P < .001, I2 = 0.0%) during the 24 hours after surgery. However, there was no statistical significance in platelet (RR = 0.613, 95% CI 0.112 to 3.348, P = .572, I2 = 0.0%) or total fresh frozen plasma (FFP) (RR = 0.511, 95% CI 0.246 to 1.063, P = .073, I2 = 0.0%) transfusion. Also, no significant difference was found in major adverse events (death or thrombotic complications) (RR = 0.917, 95% CI 0.532 to 1.581, P = .756, I2 = 0.0%) between the 2 groups. Interestingly, further subgroup analysis demonstrated that IV TXA decreased the risk of prothrombin time (PT)- and international normalized ratio (INR)-guided FFP transfusion (RR = 0.462, 95% CI 0.296 to 0.721, P = .001, I2 = 0.0%). CONCLUSION IV TXA was effective in reducing allogeneic blood component transfusion (PRBCs and PT- or INR-guided FFP transfusion), without increasing the incidence of postoperative death or thrombotic complications in off-pump CAB surgery.

Abstract

OBJECT To investigate the efficacy and safety of four interventions of spontaneous intracerebral hemorrhage simultaneously. METHODS PubMed, EmBase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) investigating endoscopic surgery (ES), minimally invasive puncture surgery (MIPS), conventional craniotomy (CC), and/or conservative medical treatment (CMT). Good functional outcome, death, and hemorrhage recurrence rates were evaluated by a network meta-analysis. RESULTS 20 RCTs with 3603 patients were included. Compared with CMT, a higher rate of good functional outcome was found after ES (RR=2.21, 95% CI 1.37 to 3.55) and MIPS (RR=1.47, 95% CI 1.24 to 1.73). Both ES (RR=0.62, 95% CI 0.44 to 0.86) and MIPS (RR=0.72, 95% CI 0.58 to 0.90) markedly reduced the rate of death. However, there was no significant difference in efficacy and safety between ES and MIPS. The top ranked P score for the efficacy outcome was for ES (P score=0.9810). ES (P-score=0.0709) ranked lowest for the primary safety outcome. There was a higher risk of hemorrhage recurrence after CC (RR=3.80, 95% CI 1.90 to 7.63) and MIPS (RR=2.86, 95% CI 1.70 to 4.82) compared with CMT whereas no significant difference was found for ES (RR=1.46, 95% CI 0.53 to 4.02). CONCLUSIONS The results suggest that both ES and MIPS significantly improve neurological function and reduce the risk of death compared with CMT, and there is no significant difference between ES and MIPS. Ranking of P scores revealed that ES may be the most optimal intervention to improve functional outcome and prevent death. This needs to be evaluated further.

Abstract

Background: Tranexamic acid (TXA) has been widely used during craniofacial and orthognathic surgery (OS). However, results of the literature are inconsistent due to specific type of surgery and a small sample of studies. The purpose of this study was to evaluate the role of TXA in bimaxillary OS. Methods: We performed a comprehensive literature search of PubMed, Cochrane Central Register of Controlled Trials, and EMBASE to identify randomized controlled trials (RCTs) that compared effect of TXA on bimaxillary OS with placebo. Outcomes of interests included intraoperative blood loss, allogenic transfusion, operation time, and volume of irrigation fluid. Random effects models were chosen considering that heterogeneity between studies was anticipated, and I (2) statistics were used to test for the presence of heterogeneity. Results: Totally 6 RCTs were identified. Tranexamic acid resulted in significantly reduced intraoperative blood loss (weighted mean difference [WMD] = -264.82 mL; 95% CI: -380.60 to -149.04 mL) and decreased amounts of irrigation fluid (WMD = -229.23 mL; 95% CI: -399.63 to -58.83 mL). However, TXA had no remarkable impact on risk of allogenic blood transfusion (pooled risk ratio = 0.50; 95% CI: 0.20-1.23), operation time (WMD = -8.71 min; 95% CI: -20.98 to 3.57 min), and length of hospital stay (WMD = -0.24 day; 95% CI: -0.62 to 0.14 day). No TXA-associated severe adverse reactions or complications were observed. Conclusions: Currently available meta-analysis reveals that TXA is effective in decreasing intraoperative blood loss; however, it does not reduce the risk of allogenic blood transfusion in bimaxillary OS.

Abstract

PURPOSE Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin's effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock. METHODS In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20-160 microg/h with maximum infusion rate of 4 mg/day) or NE (4-30 microg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population. RESULTS Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55-1.56]; p = 0.80). Change in SOFA score on day 7 was similar between the two groups: - 7 (IQR - 11 to 3) in the terlipressin group and - 6 (IQR - 10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p < 0.001). CONCLUSIONS In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events. TRIAL REGISTRATION This trial is registered at ClinicalTrials.gov: ID NCT01697410.