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1.
Safety and efficacy of double plasma molecular adsorption system with sequential low-volume plasma exchange in intermediate-stage hepatitis B virus-related acute-on-chronic liver failure
Xu W, Zhu S, Yang L, Li Z, Wu L, Zhang Y, Chen J, Deng Z, Luo Q, Peng L
Journal of medical virology. 2023
Abstract
BACKGROUND Current evidence suggests that the mortality rate of intermediate-stage hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains high. We aimed to investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-volume plasma exchange (LPE) treatment in intermediate-stage HBV-related ACLF. METHODS This prospective study recruited intermediate-stage HBV-related ACLF patients and was registered on ClinicalTrials.gov (NCT04597164). Eligible patients were randomly divided into a trial group and a control group. Patients in both groups received comprehensive medical treatment. Patients in the trial group further received DPMAS with sequential LPE. Data were recorded from baseline to week 12. RESULTS 50 patients with intermediate-stage HBV-related ACLF were included in this study. The incidence of bleeding events and allergic reactions in the trial group was 12% and 4%, respectively, with no other treatment-related adverse events. The levels of TBIL and PT-INR, and MELD scores after each session of DPMAS with sequential LPE were significantly lower than those before treatment (all p<0.05). The 12-week cumulative liver transplantation-free survival rates in the trial and control groups were 52% and 24%, respectively (p=0.041). The 12-week cumulative overall survival rates in the trial and control groups were 64% and 36%, respectively (p=0.048). The Kaplan-Meier survival analysis revealed significant differences in liver transplantation-free survival (p=0.047) and overall survival (p=0.038) between the trial and control groups. COX regression analysis indicated that BUN (p=0.038), DPMAS with sequential LPE (p=0.048) and COSSH-ACLF II score (p<0.001) were significant risk factors for mortality. CONCLUSION DPMAS with sequential LPE treatment is safe and effective for patients with intermediate-stage HBV-related ACLF. This article is protected by copyright. All rights reserved.
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2.
Evaluation of platelet-rich plasma plus basic fibroblast growth factor combined with minoxidil in the treatment of androgenetic alopecia: A randomized controlled trial
Wu S, Liu S, Chen J, Dai D, Liu W, Le D, Guan Q, Miao Y, Hu Z, Qu Q
Journal of cosmetic dermatology. 2023
Abstract
BACKGROUND Platelet-rich plasma plus basic fibroblast growth factor (PRPF) has been confirmed to be a safe and valuable therapy for androgenetic alopecia (AGA). However, the efficacy of PRPF combined with minoxidil treatment remains unknown. OBJECTIVE To assess the efficacy of combined PRPF and minoxidil treatment for AGA. METHODS In this prospective, randomized controlled trial, 75 patients with AGA were randomly divided into three groups and were administered the following treatments: Group 1, direct intradermal PRPF injection; Group 2, topical minoxidil 5% twice daily; and Group 3, PRPF injection combined with minoxidil. The PRPF injection was performed three times, 1 month apart. Hair growth parameters were evaluated using a trichoscope until the sixth month of the study. Patient satisfaction and side effects were recorded during the follow-up. RESULTS All patients showed improvements (p < 0.05) in hair count, terminal hair, and decrease in telogen hair ratio after treatment. The efficacy of PRPF complex therapy revealed significant improvements (p < 0.05) in hair count, terminal hair and growth rate, compared with monotherapy. LIMITATIONS Small sample size, short follow-up time and lack of quantification of GFs in PRPF. CONCLUSION The effect of complex therapy exceed both the effects of PRPF monotherapy and minoxidil treatment, which can be a beneficial AGA treatment strategy.
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3.
Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial
Liu B, Chen N, Zhao J, Yin A, Wu X, Xing C, Jiang G, Fu J, Wang M, Wang R, et al
Chronic diseases and translational medicine. 2022;8(2):134-144
Abstract
BACKGROUND This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. METHOD This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. CONCLUSION The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
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4.
Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority Phase III trail
Chen N, Xing C, Niu J, Liu B, Fu J, Zhao J, Ni Z, Wang M, Liu W, Zhao J, et al
Chronic diseases and translational medicine. 2022;8(1):59-70
Abstract
BACKGROUND Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia. METHODS Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. CONCLUSION Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.
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The effect of pantoprazole and somatostatin combined with thrombin in the treatment of non-esophagogastric varicosity upper gastrointestinal bleeding
Duan Y, Chen J, Cui H, Zhao C
American journal of translational research. 2021;13(5):5484-5490
Abstract
OBJECTIVE To explore the effect of pantoprazole and somatostatin combined with thrombin in the treatment of non-esophagogastric varicosity upper gastrointestinal bleeding (UGB) as well as its influence on serum hs-CRP and coagulation function. METHODS From June 2016 to May 2018, patients with upper gastrointestinal hemorrhage due to non-esophagogastric varices in our hospital were selected as research subjects. After screening, they were randomly divided into the combined group (57 cases) and the control group (57 cases). After the two groups are treated, the therapeutic effect was observed. The two groups of patients were followed up for 6 consecutive months, and the data were statistically analyzed. RESULTS It was found that there wass no significant difference between the two groups in gender, age, amount of bleeding, and etiology (P > 0.05). It was found that the immediate hemostasis rate and the hemostasis rate within 24 hours in the combined group were distinctly higher compared to the control group. The difference has statistical significance (P < 0.05). The total effective rate of the combined group was distinctly higher compared to the control group (P < 0.05). By comparing the expression levels of hs-CRP and IL-6 protein in the serum of the two groups before and after treatment, it was found that there was no significant difference in the expression levels of hs-CRP and IL-6 protein before treatment. However, after treatment, it was found that the levels of hs-CRP and IL-6 protein in the combined group were distinctly lower compared to the control group (P < 0.05). By analyzing adverse reactions, it was found that the combined group had distinctly lower adverse reactions compared to the control group (P < 0.05). CONCLUSION This work provides an experimental basis for the diagnosis and treatment of non-esophagogastric varicose UGB in the clinic.
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The pharmacodynamic effect of terlipressin versus high-dose octreotide in reducing hepatic venous pressure gradient: a randomized controlled trial
Li B, Chen J, Zhang CQ, Wang GC, Hu JH, Luo JJ, Zhang W, Wei YC, Zeng XQ, Chen SY
Annals of translational medicine. 2021;9(9):793
Abstract
BACKGROUND Vasoactive drugs can reduce portal venous pressure and control variceal bleeding. However, few studies have explored the hemodynamic effects of terlipressin and high-dose octreotide in such patients. Our purpose was to evaluate the hemodynamic changes and safety of using terlipressin and high-dose octreotide in patients with decompensated liver cirrhosis. METHODS A multi-center randomized controlled trial was conducted. Cirrhotic patients with a history of variceal bleeding were included. Terlipressin or high-dose octreotide was administered during the procedure of measuring hepatic venous pressure gradient (HVPG). Hemodynamic parameters and symptoms were recorded. RESULTS A total of 88 patients were included. HVPG was significantly reduced at 10, 20, and 30 min after drug administration in the terlipressin group (16.3±6.4 vs. 14.7±5.9, 14.0±6.1, and 13.8±6.1, respectively, P<0.001) and the high-dose octreotide group (17.4±6.6 vs. 15.1±5.8, 15.3±6.2, and 16.1±6.0, respectively P<0.01). Decreased heart rate and increased mean arterial pressure were more often observed in the terlipressin group. The overall response rates were not significantly different between the groups (52.8% vs. 44.8%, P=0.524). The terlipressin group had significantly higher response rates at 30 min compared to the high-dose octreotide group in those with alcoholic liver cirrhosis [6/6 (100%) vs. 0/4 (0%), P=0.005]. The incidence of adverse drug events was rare and similar in the two groups. CONCLUSIONS Both terlipressin and high-dose octreotide were effective and safe for reducing HVPG. The pharmacodynamic effect of terlipressin persisted longer. The terlipressin group had higher response rates in those with alcoholic cirrhosis (trial number: NCT02119884).
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Cognitive and physical performance are well preserved following standard blood donation: A noninferiority, randomized clinical trial
Nadler R, Tsur AM, Lipsky AM, Lending G, Benov A, Ostffeld I, Shinar E, Yanovich R, Moser A, Levy D, et al
Transfusion. 2020
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Editor's Choice
Abstract
BACKGROUND A walking blood bank (WBB) refers to the use of fellow combatants for battlefield blood donation. This requires pretesting combatants for infectious diseases and blood type. A fundamental prerequisite for this technique is that the donating soldier will suffer minimal physiological and mental impact. The purpose of the current study is to assess the effect of blood shedding on battlefield performance. METHODS This is a double-blind randomized control trial. Forty Israel Defense Forces combatants volunteered for the study. Participants underwent baseline evaluation, including repeated measurement of vital signs, cognitive evaluation, physical evaluation, and a strenuous shooting test. Three weeks after the baseline evaluation, subjects were randomized to either blood donation or the control group. For blinding purposes, all subjects underwent venous catheterization for the duration of a blood donation. Repeated vital signs and function evaluation were then performed. RESULTS Thirty-six patients were available for randomization. Baseline measurements were similar for both groups. Mean strenuous shooting score was 80.5 +/- 9.5 for the control group and 82 +/- 6.6 for the test group (p = 0.58). No clinically or statistically significant differences were found in tests designed to evaluate cognitive performance or physical functions. Vital signs taken multiple times were also similar between the test and control groups. CONCLUSIONS Executive, cognitive, and physical functions were well preserved after blood donation. This study supports the hypothesis that a WBB does not decrease donor combat performance. The categorical prohibition of physical exercise following blood donation might need to be reconsidered in both military and civilian populations.
PICO Summary
Population
Infantry combatants (n= 36).
Intervention
Blood donation group: 450ml of blood collected after venous catheterisation (n= 18).
Comparison
Control group: venous catheterisation (n= 18).
Outcome
No clinically or statistically significant differences were found in tests designed to evaluate cognitive performance or physical functions. Vital signs taken multiple times were also similar between the test and control groups.
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A prospective, single-blind, randomized, phase III study to evaluate the safety and efficacy of Fibrin Sealant Grifols as an adjunct to hemostasis compared with manual compression in vascular surgery
Nenezic D, Ayguasanosa J, Menyhei G, Tamas H, Matyas L, Muluk S, Courtney K, Ibanez J, Chen J
Journal of vascular surgery. 2019
Abstract
OBJECTIVE New formulations and applications of hemostatic adjuncts such as fibrin sealant (FS) to support local hemostasis and sutures continue to be developed. In a pivotal, confirmatory, controlled, prospective, single-blinded, randomized, multicenter phase III clinical trial, the efficacy and safety of FS Grifols during vascular surgeries were evaluated. METHODS Patients undergoing a nonemergency, open, peripheral vascular surgical procedure with moderate arterial bleeding were recruited. In an initial preliminary part of the study, all patients were treated with FS Grifols. In a subsequent primary part, patients were randomized (2:1) to FS Grifols or manual compression (MC). The primary efficacy end point was the proportion of the primary part patients achieving hemostasis by 4 minutes after the start of treatment. Cumulative proportion and time to hemostasis were secondary efficacy end points. Safety end points (in pooled preliminary and primary parts) included adverse events (AEs), vital signs, physical assessments, clinical laboratory tests, viral markers, and immunogenicity. RESULTS The primary efficacy end point was met by 76.1% of patients (83/109) for the FS Grifols group versus 22.8% of patients (13/57) for the MC group (P < .001). The cumulative proportion of patients at 5, 7, and 10 minutes was 80.7%, 84.4%, and 88.1%, respectively, in the FS Grifols treatment group, and 28.1%, 35.1%, and 45.6% in the MC treatment group (P < .001). The median time to hemostasis was shorter in the FS Grifols group (4 minutes vs ≥10 minutes in the MC group; P < .001). The nature of AEs reported were those expected in the study patient profile. The percentage of patients experiencing treatment-emergent AEs were similar in both the FS Grifols (pooled n = 59 + 109) and MC groups (81.0% and 77.2%, respectively), most recurrent being procedural pain (34.5% and 36.8%, respectively) and pyrexia (11.3% and 10.5%, respectively). CONCLUSIONS FS Grifols was superior in efficacy and similar in safety to MC as an adjunct local hemostatic agent in patients undergoing open vascular surgeries.
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Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial
Liu ZM, Chen J, Kou Q, Lin Q, Huang X, Tang Z, Kang Y, Li K, Zhou L, Song Q, et al
Intensive Care Medicine. 2018;44((11):):1816-1825
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.
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A Prospective, Single-Blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Soft Tissue Open Surgery
Lakshman S, Aqua K, Stefanovic A, Djurdjevic S, Nyirady P, Osvath P, Davis R, Bullock A, Chen J, Ibanez J, et al
Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research. 2018;:1-13.
Abstract
BACKGROUND/PURPOSE Rapid hemostasis, an essential prerequisite of good surgical practice during surgical bleeding, including soft tissue open surgery, often requires adjunctive treatment. We evaluated the safety and hemostatic effectiveness of a human plasma-derived fibrin sealant (FS Grifols) in soft tissue open surgery. METHODS Patients with moderate soft tissue bleeding during open, urologic, gynecologic or general surgery were studied. The trial consisted of a preliminary phase (to familiarize investigators with the technique for FS Grifols application and the intraoperative procedures required by the clinical protocol) and a primary phase: in both phases, patients were randomized 1:1 to FS Grifols or Surgicel((R)). The primary efficacy endpoint, based on analysis of subjects in the primary phase of the study, was to evaluate whether FS Grifols was non-inferior to Surgicel((R)) in achieving hemostasis, based on the proportion of subjects in both treatment groups who achieved hemostasis at the target bleeding site (TBS) by 4 min (T4) following the start of treatment application. Safety assessments included adverse events (AEs), vital signs, physical assessments, common clinical laboratory tests, viral markers, and immunogenicity. RESULTS A total of 224 subjects were randomized (primary phase): FS Grifols (N = 116), Surgicel((R)) (N = 108). The 95% CI at T4 for the ratio of the proportion of patients achieving hemostasis in the two treatment groups was 1.064 (0.934, 1.213), indicating non-inferiority for FS Grifols vs. Surgicel((R)). The rate of hemostasis at the TBS by T4 in both phases of the study was higher in the FS Grifols treatment group (preliminary phase: 90.2%; primary phase: 82.8%) than in the Surgicel((R)) treatment group (preliminary phase: 78.8%; primary phase: 77.8%). Overall, reported AEs were as expected in surgical patients and were similar between the two treatment groups. CONCLUSIONS This study shows the non-inferiority in time to hemostasis of FS Grifols vs. Surgicel as an adjunct to hemostasis in patients undergoing soft tissue open surgery, and a similar rate of AEs.