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1.
Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis
Zheng Q, Zhang P, Yang H, Geng Y, Tang J, Kang Y, Qi A, Li S
Heliyon. 2023;9(4):e15310
Abstract
AIMS: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. METHODS PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. KEY FINDINGS Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, -0.45 to 1.75; very low certainty; SMD, -0.03; 95% CI, -0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, -15.06, 95%CI, -21.96 to -8.16; low certainty; MD, -18.07; 95% CI, -30.05 to -6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. SIGNIFICANCE HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.
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Significant association between anemia and higher risk for COVID-19 mortality: A meta-analysis of adjusted effect estimates
Wang Y, Nan L, Hu M, Zhang R, Hao Y, Wang Y, Yang H
The American journal of emergency medicine. 2022;58:281-285
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Abstract
OBJECTIVE This study aimed to evaluate whether there was a significant relationship between anemia and the risk for mortality among coronavirus disease 2019 (COVID-19) patients by a quantitative meta-analysis based on the adjusted effect estimates. METHODS A systematic search was conducted in electronic databases to identify all published literature. A random-effects meta-analysis model was used to estimate the pooled effect size and 95% confidence interval (CI). Heterogeneity test, Begg's test, subgroup analysis and meta-regression were performed. RESULTS Twenty-three articles with 573,928 COVID-19 patients were included in the quantitative meta-analysis. There was a significant association between anemia and an elevated risk of COVID-19 mortality (pooled effect size = 1.47, 95% CI [1.30-1.67]). We observed this significant association in the further subgroup analyses by age, proportion of males, sample size, study design, region and setting. Sensitivity analysis exhibited that our results were reliable. Begg's test showed that there was no publication bias. Meta-regression indicated that the tested variables might not be the source of heterogeneity. CONCLUSION Our meta-analysis based on risk factors-adjusted effect estimates indicated that anemia was independently associated with a significantly elevated risk for mortality among COVID-19 patients.
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Efficacy and safety of double-filtration plasmapheresis treatment of myasthenia gravis: A systematic review and meta-analysis
Liu C, Liu P, Ma M, Yang H, Qi G
Medicine. 2021;100(17):e25622
Abstract
OBJECTIVES To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.
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Prognostic Value of Bleeding in Gastrointestinal Stromal Tumors: A Meta-Analysis
Fan X, Han H, Sun Z, Zhang L, Chen G, Mzee SAS, Yang H, Chen J
Technology in cancer research & treatment. 2021;20:15330338211034259
Abstract
BACKGROUND Gastrointestinal bleeding is the most common clinical manifestation of gastrointestinal stromal tumor. It is of great significance to the prognosis of patients. But the results are controversial. The purpose of this study was to evaluate the relationship between gastrointestinal bleeding and clinical prognosis in patients with GIST. METHODS A systematic literature search was performed in Pumbed, Cochrane Library, EMBASE, ClinicalTrials.gov, CNKI, VIP and wanfang databases with the pattern of unlimited languages. 12 studies with 2781 individuals were included in the final analysis. The overall survival (OS), recurrence-free survival/disease-free survival (RFS/DFS) and related factors affecting bleeding in patients with gastrointestinal stromal tumor (GIST) were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were used for in the meta-analysis. RESULTS A total of 12 articles were included in the study, including 2781 patients with GIST, including 845 patients with gastrointestinal bleeding. The OS of GIST patients with gastrointestinal bleeding was significantly worse (HR = 2.54, 95% CI = 1.13-5.73, P = 0.025). But there was no significant difference in RFS between gastrointestinal bleeding patients and non-bleeding patients (HR = 1.35, 95% CI = 0.70-2.61, P = 0.371). Further analysis of the related factors of GI bleeding in GIST patients was observed, besides the aging factor (HR = 1.02, 95% CI = 0.69-1.50, P = 0.929), Small intestinal stromal tumor (HR = 0.56, 95% CI = 0.41-0.76, P < 0.001), tumor diameter ≥ 5 cm (HR = 2.09, 95% CI = 1.20-3.63, P = 0.009), Mitotic index ≥ 5/50 HPF (HR = 1.66, 95% CI = 1.11-2.49, P = 0.014) and tumor rupture (HR = 2.04, 95% CI = 1.0-3.82, P = 0.026) all increased the risk of GI bleeding in patients with GIST. CONCLUSIONS The OS of GIST patients with GI bleeding was worse than non-GI bleeding, but had no significant effect on RFS. Nevertheless the aging factor, the location of GIST in the small intestine, tumor diameter ≥ 5 cm, Mitotic index ≥ 5/50 HPF and tumor rupture all increased the risk of GI bleeding in patients with GIST.
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Comparison of oral versus intravenous tranexamic acid in total knee and hip arthroplasty: A GRADE analysis and meta-analysis
Sun C, Zhang X, Chen L, Deng J, Ma Q, Cai X, Yang H
Medicine. 2020;99(44):e22999
Abstract
BACKGROUND The efficacy and safety of oral tranexamic acid (TXA) remain controversial because of the small number of clinical studies. The aim of the present study was to compare the efficacy and safety of oral TXA with intravenous TXA in patients undergoing total hip arthroplasty and total knee arthroplasty in a systematic review and meta-analysis. METHODS We conducted a meta-analysis to identify randomized controlled trials (RCTs) involving oral and intravenous TXA in total hip arthroplasty and total knee arthroplasty up to December 2019 by searching databases including PubMed, Web of Science, Embase, the Cochrane Controlled Trials Register, the Cochrane Library China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang. The mean difference or standard mean difference was used to assess continuous outcomes such as hemoglobin (Hb) drop, total blood loss, drain blood loss, and length of hospital stay, with a 95% confidence interval. Relative risks with a 95% confidence interval were used to assess dichotomous outcomes such as transfusion rate and the incidence of deep venous thrombosis and calf muscular vein thrombosis. Review Manager was used for the meta-analysis. RESULTS Ten RCTs containing 1080 participants met the inclusion criteria. We found no significant differences in terms of the average Hb drop (P = .60), total blood loss (P = .60), transfusion rate (P = .99), drain blood loss (P = .91), length of hospital stay (P = .95), and the incidence of deep venous thrombosis (P = .55) and calf muscular vein thrombosis (P = .19) between oral and IV TXA. CONCLUSIONS Compared with the IV TXA, oral TXA has similar effects on reducing the Hb drop, total blood loss, transfusion rate, drain blood loss, and length of hospital stay without increasing the risk of calf muscular vein thrombosis and deep venous thrombosis. Furthermore, oral TXA is easy to access and administer, which decreases the workload of nurses and even delivers cost-saving benefits to the health care system. We thus conclude that oral TXA may be an optimal approach in total joint arthroplasty. However, more high-quality and multicenter RCTs are still needed to confirm our conclusions. REGISTRATION The current meta-analysis was registered on PROSPERO (International Prospective Register of Systematic Reviews), and the registration number was CRD42018111291.
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Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis
Zheng Q, Wang Y, Yang H, Sun L, Fu X, Wei R, Liu YN, Liu WJ
Frontiers in pharmacology. 2020;11:573645
Abstract
Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.
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Efficacy and safety of HIF prolyl-hydroxylase inhibitor vs epoetin and darbepoetin for anemia in chronic kidney disease patients not undergoing dialysis: a network meta-analysis
Zheng Q, Yang H, Sun L, Wei R, Fu X, Wang Y, Huang Y, Liu YN, Liu WJ
Pharmacol Res. 2020;:105020
Abstract
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and http://clinicaltrials.gov/ clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95% confidence interval [CI]: 0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95% CI: 0.933.99) for desidustat, 1.81 (0.872.75) for enarodustat, 1.68 (0.642.72) for molidustat, 1.66 (0.892.44) for epoetin, 1.63 (0.692.56) for darbepoetin, 1.61 (0.992.22) for roxadustat, and 1.55 (0.742.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95% CI, 0.062.59]; roxadustat, 0.40 (0.062.84); enarodustat, 0.33 (0.0116.25); desidustat, 0.34 (0.0117.00); epoetin, 0.50 (0.181.42); daprodustat, 0.54 (0.093.31); darbepoetin, 1.03 (0.651.65); and vadadustat, 1.43 (0.1513.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.
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Additive effectiveness of autologous platelet-rich fibrin in the treatment of intrabony defects: A PRISMA-compliant meta-analysis
Li A, Yang H, Zhang J, Chen S, Wang H, Gao Y
Medicine. 2019;98(11):e14759
Abstract
BACKGROUND This meta-analysis was performed to determine the additive effectiveness of autologous platelet-rich fibrin in the treatment of intrabony defects in chronic periodontitis patients. METHODS Pertinent studies were identified by a search in Medline, EMBASE, the Web of Science, and the Cochrane Library. The trials searched were evaluated for eligibility. Cochrane Collaboration's Review Manager software was used to perform the meta-analyses. RESULTS Twelve eligible clinical trials were included. Pooled data found that adjunctive platelet-rich fibrin exactly yielded a significantly superior probing depth reduction compared with open flap debridement alone (weighted mean difference, 1.01; 95% confidence interval 0.95-1.08; P < .00001). The clinical attachment level (CAL) gain after treatment for 9 months was higher in patients treated with platelet-rich fibrin plus open flap debridement group than in open flap debridement-treated patients (weighted mean difference, 1.29; 95% confidence interval 0.96- 1.61; P < .00001). Similarly, the meta-analysis demonstrated that platelet-rich fibrin was superior to single open flap debridement with respect to gingival marginal level change (weighted mean difference, 0.45; 95% confidence interval 0.31-0.58; P < .00001). Regarding the hard tissue radiographic parameters, including defect depth reduction and percentage of fill defects in bone, adjunctive platelet-rich fibrin yielded significantly superior results compared with open flap debridement alone. CONCLUSION Adjunctive use of platelet-rich fibrin with open flap debridement significantly improves fill defects when compared to open flap debridement alone. However, additional powered studies with much larger sample sizes are needed to obtain a more concrete conclusion.
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Indirect-comparison meta-analysis of treatment options for patients with refractory Kawasaki disease
Chan H, Chi H, You H, Wang M, Zhang G, Yang H, Li Q
BMC pediatrics. 2019;19(1):158
Abstract
BACKGROUND There is limited information available regarding the clinical management of intravenous immunoglobulin-resistant Kawasaki disease (KD). We aimed to evaluate the optimal treatment options for patients with refractory KD by presenting an indirect-comparison meta-analysis. METHODS PubMed, EMBASE, Web of Science, and the Cochrane Database were searched on August 31, 2018. Unpublished studies were also searched in ProQuest Dissertations & Theses and through manual retrieval strategies. Randomized concurrent controlled trials (RCTs), high-quality non-randomized concurrent controlled trials (non-RCTs), and retrospective studies associated with AEs were included. The quality of all eligible studies was assessed using Cochrane collaboration's tool and non-randomized study guidelines. Risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes were estimated in our analysis. GRADE profiler 3.6.1 was used to assess the evidence profile. RESULTS Twelve studies involving 372 immunoglobulin-resistant KD patients were identified and analyzed. Neither infliximab nor intravenous pulse methylprednisolone (IVMP) was significantly more effective than second IVIG infusion with respect to lowering coronary artery lesions (CALs) (infliximab, 0.85, 0.43-1.69; IVMP, 0.99, 0.52-1.88) and treatment resistance (infliximab, 0.43, 0.21-0.89; IVMP, 1.16, 0.33-4.13). No significant differences were found between infliximab and IVMP in the incidence rate of CALs (0.70, 0.27-1.81), the treatment resistance (0.37, 0.09-1.60), the rates of coronary artery aneurysm (4.13, 0.38-45.22) and the coronary artery dilatation (0.45, 0.10-1.99). Furthermore, compared with second IVIG infusion, both infliximab and IVMP showed significant effectiveness in antipyretic effects (infliximab, 1.52, 1.16-1.99; IVMP, 1.29, 0.77-2.15). However, Infliximab was noninferior to IVMP on antipyretic effects (1.18, 0.66-2.15). IVMP treatment showed significant association with fewer AEs than second IVIG infusion (0.49, 0.26-0.94) and infliximab (2.34, 1.07-5.09). No significant differences were noted between infliximab treatment and second IVIG infusion (1.06, 0.69-1.63). CONCLUSIONS Infliximab, IVMP, and second IVIG infusion showed no significant differences in the cardioprotective effect or the rate of treatment resistance. Infliximab and IVMP treatment were more effective than second IVIG infusion regarding antipyretic effects. IVMP treatment may have an advantage due to its lower total rate of AEs associated with drug infusion. TRIAL REGISTRATION The study has been registered on PROSPERO ( CRD42016039693 ).
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Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update
Bohlius J, Bohlke K, Castelli R, Djulbegovic B, Lustberg MB, Martino M, Mountzios G, Peswani N, Porter L, Tanaka TN, et al
Blood advances. 2019;3(8):1197-1210
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Abstract
PURPOSE To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines.
PICO Summary
Population
Patients with cancer or chronic kidney disease (17 studies).
Intervention
Erythropoiesis-stimulating agents (ESAs) including biosimilars.
Comparison
Addition of iron to an ESA, placebo or best standard therapy.
Outcome
A growing body of evidence suggested that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of red blood cell transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remained limited.