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
Chronic diseases and translational medicine. 2022;8(1):59-70
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.
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
Chronic diseases and translational medicine. 2022;8(2):134-144
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.
Can Artificial Intelligence Be Applied to Diagnose Intracerebral Hemorrhage under the Background of the Fourth Industrial Revolution? A Novel Systemic Review and Meta-Analysis
International journal of clinical practice. 2022;2022:9430097
AIM: We intended to provide the clinical evidence that artificial intelligence (AI) could be used to assist doctors in the diagnosis of intracerebral hemorrhage (ICH). METHODS Studies published in 2021 were identified after the literature search of PubMed, Embase, and Cochrane. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to perform the quality assessment of studies. Data extraction of diagnosis effect included accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), area under curve (AUC), and Dice scores (Dices). The pooled effect with its 95% confidence interval (95%CI) was calculated by the random effects model. I-Square (I (2)) was used to test heterogeneity. To check the stability of the overall results, sensitivity analysis was conducted by recalculating the pooled effect of the remaining studies after omitting the study with the highest quality or the random effects model was switched to the fixed effects model. Funnel plot was used to evaluate publication bias. To reduce heterogeneity, recalculating the pooled effect of the remaining studies after omitting the study with the lowest quality or perform subgroup analysis. RESULTS Twenty-five diagnostic tests of ICH via AI and doctors with overall high quality were included. Pooled ACC, SEN, SPE, PPV, NPV, AUC, and Dices were 0.88 (0.83∼0.93), 0.85 (0.81∼0.89), 0.90 (0.88∼0.92), 0.80 (0.75∼0.85), 0.93 (0.91∼0.95), 0.84 (0.80∼0.89), and 0.90 (0.85∼0.95), respectively. There was no publication bias. All of results were stable as revealed by sensitivity analysis and were accordant as outcomes via subgroups analysis. CONCLUSION Under the background of the fourth industrial revolution, AI might be an effective and efficient tool to assist doctors in the clinical diagnosis of ICH.
Efficacy of Intraoperative Platelet-Rich Plasma Augmentation and Postoperative Platelet-Rich Plasma Booster Injection for Rotator Cuff Healing: A Randomized Controlled Clinical Trial
Orthopaedic journal of sports medicine. 2021;9(6):23259671211006100
BACKGROUND Platelet-rich plasma (PRP) has been applied as an adjuvant treatment for arthroscopic rotator cuff repair (ARCR) to enhance rotator cuff healing. However, it remains debatable whether PRP enhances tendon-to-bone healing. PURPOSE To assess the efficacy of intraoperative augmentation and postoperative injection of PRP that was prepared using the double-spin method and calcium activation without thrombin in patients with ARCR. STUDY DESIGN Randomized controlled trial; Level of evidence, 1; and cohort study; Level of evidence, 3. METHODS A total of 58 patients underwent ARCR using intraoperative PRP augmentation. Half of the patients were randomly assigned to receive an additional ultrasound-guided PRP injection at the repair site at 2 weeks postoperatively (PRP-booster group); the other half did not receive the booster injection (PRP-only group). A control group that did not receive any PRP treatment was retrospectively matched using propensity score matching. Structural integrity was assessed using magnetic resonance imaging at 1 year postoperatively, and healing rates were compared between patients with tear sizes ≤2 cm versus >2 cm. Functional outcomes were assessed using the visual analog scale (VAS) for pain; VAS for satisfaction; shoulder range of motion; and Constant, American Shoulder and Elbow Surgeons, and Simple Shoulder Test scores at minimum 2-year follow-up. RESULTS In patients with tears >2 cm, the rate of healing failure at 1-year follow-up was significantly less in the overall PRP group than in the control group (12.9% vs 35.7%, respectively; P = .040), however, the PRP-booster group did not present a better healing rate than did the PRP-only group. The overall PRP group had lower VAS for pain scores compared with the control group (0.5 ± 1.1 vs 1.3 ± 1.8, respectively; P = .016) and higher VAS for satisfaction scores (9.2 ± 1.2 vs 8.6 ± 1.7; P = .023) at the final follow-up, whereas no statistical difference was found between the PRP-only and PRP-booster groups in functional outcomes. CONCLUSION Intraoperative PRP augmentation during ARCR demonstrated superior anatomic healing results in patients with rotator cuff tears >2 cm as well as reduced pain and increased subjective satisfaction. PRP booster injection provided no additional benefit to tendon integrity or functional recovery.
Assessment of Bone Formation After Secondary Alveolar Bone Grafting With and Without Platelet-Rich Plasma Using Computer-Aided Engineering Techniques
The Journal of craniofacial surgery. 2020
The aim of this study was to analyze the newly formed bone volume (FV), 6 months after secondary alveoloplasty using iliac cancellous bone graft, with and without platelet-rich plasma (PRP). Forty patients with unilateral alveolar cleft were involved in this randomized, prospective, comparative study, with 20 patients each forming the control (group A) and PRP (group B) groups, respectively. The preoperative alveolar defect volume (DV) and the postoperative FV were automatically calculated by the computer-aided engineering software using the patients' pre and postsurgical computed tomography data. The volume of the actual bone graft (AV) was identical to the DV calculated before surgery. The bone formation ratio (BF%) was calculated as follows: BF% = (FV/AV) x 100%. The mean BF% was 42.54 +/- 9.32% in group A and 46.97 +/- 18.49% in group B. There was no statistically significant difference between the 2 groups for BF% (P > 0.05). The study presents a fast and accurate method for assessing the effect of PRP in alveolar grafting. However, the study found no conclusive evidence on the effect of PRP on bone growth.
Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies
Sleep medicine. 2019
OBJECTIVE Restless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity. METHOD The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0. RESULTS This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21-5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score. CONCLUSION The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.
Effect of continuous plasma filtration adsorption on treatment of severely burned patients with sepsis
Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns. 2018;34((6)):370-373.
Objective: To investigate effect of continuous plasma filtration adsorption on treatment of severely burned patients with sepsis. Methods: In January 2014 to September 2017, 86 severely burned patients with sepsis, conforming to the study criteria, were admitted to our hospital and divided into into routine treatment group and continuous plasma filtration group according to the random number table method, with 43 patients in each group. Patients in routine treatment group were treated with routine treatment after admission. Patients in continuous plasma filtration group were treated with blood filter, blood purification machine, and plasma separator for continuous plasma filtration adsorption on the basis of the routine treatment group on the second day after admission. The course of treatment in the 2 groups was 7 d. The total effective treatment rate, changes of leukocyte count (WBC), usea nitrogen, serum creatinine, neutrophile CD64, procalcitonin, and C reactive protein (CRP) before and after treatment, and mortality on 28 days after treatment of patients in 2 groups were analyzed and compared. Results: (1) The total effective treatment rate of patients in continuous plasma filtration group was 88.37% (38/43), which was significantly higher than that of the routine treatment group [65.12% (28/43), chi(2)=6.515, P=0.018]. (2) After treatment, WBC, urea nitrogen, serum creatinine, neutrophils CD64, procalcitonin, and CRP of patients in continuous plasma filtration group were significantly lower those in routine treatment group (t=6.305, 4.420, 18.537, 13.435, 12.975, 14.234, P<0.05). WBC, urea nitrogen, serum creatinine, neutrophile CD64, procalcitonin, and CRP of patients in 2 groups after treatment were significantly lower than those before treatment (t=9.459, 9.130, 25.438, 35.467, 23.471, 23.601, 3.802, 5.662, 12.067, 25.694, 20.720, 12.437, P<0.05). (3) On 28 days after treatment, mortality of patients in continuous plasma filtration group was 6.98% (3/43), which was significantly lower than that in routine treatment group [25.58% (11/43)], chi(2)=5.460, P=0.023. Conclusions: Continuous plasma filtration adsorption is effective in treating severely burned patients with sepsis, which can alleviate inflammatory reaction mediated by inflammatory cytokine with good prognosis.
Hidden and overall haemorrhage following minimally invasive and open transforaminal lumbar interbody fusion
Journal of Orthopaedics and Traumatology : Official Journal of the Italian Society of Orthopaedics and Traumatology. 2017;18((4):):395-400
BACKGROUND Hidden haemorrhage has been proved to be significant in joint surgery. However, when referring to lumbar interbody fusion, it is often ignored because of its invisibility. This randomized controlled study aimed to calculate and compare hidden haemorrhage following minimally invasive and open transforaminal lumbar interbody fusion (MIS-TLIF and open TLIF). Meanwhile, its clinical significance was also analyzed. MATERIALS AND METHODS A total of 41 patients were included in this study, then they were randomized to receive MIS-TLIF or open TLIF, 21 and 20, respectively. For each case, total volume loss of red blood cell (RBC) was calculated by Gross' formula based on perioperative haematocrit change, then perioperative visible volume loss of RBC was calculated through haemorrhage volume and weight. After deducting it from total volume loss of RBC, hidden volume loss of RBC was obtained. Absolute amount of hidden haemorrhage and its ratio upon total haemorrhage, as well as indicators assessing clinical outcomes, including visual analogue scale (VAS) for back and leg, Oswestry disability index (ODI), interbody fusion rate and complication incidence were compared and analyzed. RESULTS Mean hidden volume loss of RBC in MIS-TLIF was significantly reduced compared with open TLIF (166.7 versus 245.6 ml). Besides, both mean total and visible volume loss of RBC in MIS-TLIF were also statistically less than those in open TLIF (355.3 versus 538.6 ml; 188.6 versus 293.0 ml). While mean ratio of hidden haemorrhage upon total haemorrhage was 46.7% for MIS-TLIF and 44.5% for open TLIF, respectively, showing no statistical significance. At one week postoperatively, more significant improvements of VAS for back and leg, as well as ODI were seen in MIS-TLIF compared with open TLIF. While at final follow-up of at least 2 years, all parameters continued to improve and revealed no statistical difference between both surgeries. Similar interbody fusion rate and complication incidence were observed in both series. CONCLUSIONS Besides reduced visible haemorrhage and improved clinical outcomes, MIS-TLIF also owns the superiority of less hidden haemorrhage, offering another advantage over open TLIF. LEVEL OF EVIDENCE Level II.
Systematic review of transfusion strategies for cardiac surgery . Chinese
Shengwu Yixue Gongchengxue Zazhi/Journal of Biomedical Engineering. 2014;31((2):):319-26.
This paper is aimed to assess the effects of red blood cell (RBC) transfusion on clinical outcomes in cardiac surgery. Trials were identified by computer searches of the Pubmed, MEDLINE, Cochrane Library (Issue 10, 2012), from January 1980 to October 2012. References in identified trials and review articles were checked and experts contacted to identify any additional trials. The homogeneous randomized controlled trials (RCTs) were analyzed with RevMan 5.1 software. Five trials involving a total of 1,203 patients were identified. The results of meta-analyses showed that restrictive transfusion strategies reduced the risk of receiving a RBC transfusion (MD = - 1.46, 95% CI -1.18(-) -1.1) and the volume of RBCs transfusion (RR = 0.69, 95% CI 0.53-0.89). No significant difference was noted between the two strategies in terms of mortality, adverse events and hospital or intensive care length of stay. Based on the results mentioned above, one can draw a conclusion that restrictive transfusion strategies reduced the risk of receiving RBC transfusion and the volume of RBCs transfused. Restrictive transfusion strategies did not appear to impact on the rate of adverse events and hospital or intensive care length of stay, compared to liberal transfusion strategies.
Half-dose aprotinin does not affect haemorheological properties in patients undergoing bypass surgery
Coronary Artery Disease. 1996;7((8):):609-13.
OBJECTIVE To investigate haemorheological changes in patients undergoing coronary artery bypass grafting and to determine whether the protective effect on haemorheology of high-dose aprotinin also exists under a half-dose regimen. METHODS Forty patients were studied in a double-blind, placebo-controlled study design. Patients in the aprotinin group received half of the standard high dose of aprotinin during surgery. Erythrocyte and white-cell clogging rates as well as whole blood and plasma viscosity were measured. Viscosity results were expressed as a ratio to the viscosity of saline. RESULTS Erythrocyte and white-cell clogging rates were increased significantly, whereas whole blood and plasma viscosity were decreased significantly during cardiopulmonary bypass. The reduction in viscosity had a strong correlation to haemodilution. There was no significant difference in any of the measured variables between the aprotinin and the placebo groups. CONCLUSION This study showed that blood cell damage occurred during cardiopulmonary bypass surgery, as measured by a raised clogging rate. This tendency was the same in both groups and therefore no increased potential for microthrombi could be attributed to aprotinin haemorheologically. However, half-dose aprotinin did not show any preserving effect in haemorheology when the blood-cell clogging rate and blood viscosity were studied.