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Recombinant human erythropoietin plus methylprednisolone versus methylprednisolone in treatment of acute spinal cord injury:protocol for a systematic review and meta-analysis
Fang, M., Zhou, J., Huang, S., Zhang, Y., He, Y., Zeng, Y., Song, Y.
BMJ open. 2022;12(12):e056689
Abstract
INTRODUCTION Recent studies in animal models indicate that recombinant human erythropoietin (rHuEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). We described a protocol aimed at evaluating the efficacy of rHuEPO plus methylprednisolone (MP) compared with MP alone in improving neurological function of patients with SCI in randomised controlled trials (RCTs). METHODS AND ANALYSIS This study aims to explore the effect of rHuEPO combined with MP on neurological function in patients with SCI through a meta-analysis. To this end, the authors will search eight research databases for data retrieval: MEDLINE, China National Knowledge Infrastructure, Wan Fang, China Biology Medicine dis, Web of Science, PubMed, Cochrane and Embase for RCTs on SCI in any language. The primary outcome will be the American Spinal Injury Association score at the time of follow-up. The secondary outcomes will be the WHOQOL-100 instrument score, neurophysiological state and related factors. Two authors will independently search literature records, scan titles, abstracts and full texts, collect data, and assess materials for risk of bias. Stata V.14.0 will be used for statistical analysis. ETHICS AND DISSEMINATION This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in scientific conferences and a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42021260688.
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Efficacy and safety of high and low dose recombinant human erythropoietin on neurodevelopment of premature infants: A meta-analysis
Qin N, Qin H
Medicine. 2021;100(18):e25805
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Abstract
BACKGROUND To evaluate the effect of recombinant human erythropoietin (rhEPO) in nervous system of premature infants including different dosage. METHODS The multiple databases like Pubmed, Embase, Cochrane databases and China National Knowledge Database were used to search for the relevant studies, and full-text articles involved in the evaluation on effect of rhEPO for neurodevelopment among premature infants. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted. RESULTS Finally, 10 eligible studies were eventually satisfied the included criteria. The results showed that rhEPO was much higher than placebo group in composite cognitive score (MD = 5.89, 95% confidential interval {CI} [1.95, 9.82], P = .003; I2 = 89%), there was no significant difference between rhEPO and placebo groups (RR = 0.93, 95% CI [0.60, 1.43], P = .74; I2 = 51%) and no difference in neurodevelopmental impairment between rhEPO and placebo was insignificant (RR = 0.55 95% CI [0.30, 1.02], P = .06). Composite cognitive score in high dose rhEPO was much higher than placebo group (MD = 10.39, 95% CI [8.84, 11.93], P < .0001, I2 = 0%) and low dose rhEPO also had higher composite cognitive score than placebo group (MD = 2.58, 95% CI [0.80, 4.37], P = .004, I2 = 11%). Limited publication bias was observed in this study. CONCLUSION Recombinant human erythropoietin might be a promotor for neurodevelopment among premature infants with limited adverse events.
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Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis
Ivain P, Montaldo P, Khan A, Elagovan R, Burgod C, Morales MM, Pant S, Thayyil S
Journal of perinatology : official journal of the California Perinatal Association. 2021;41(9):2134-2140
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Editor's Choice
Abstract
OBJECTIVE We examined whether erythropoietin monotherapy improves neurodevelopmental outcomes in near-term and term infants with neonatal encephalopathy (NE) in low-middle income countries (LMICs). METHODS We searched Pubmed, Embase, and Web of Science databases to identify studies that used erythropoietin (1500-12,500 units/kg/dose) or a derivative to treat NE. RESULTS Five studies, with a total of 348 infants in LMICs, were retrieved. However, only three of the five studies met the primary outcome of death or neuro-disability at 18 months of age or later. Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later (p < 0.05). Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56 (95% CI: 0.42-0.75)). CONCLUSION The pooled data suggest that erythropoietin monotherapy may improve outcomes after NE in LMICs where therapeutic hypothermia is not available.
PICO Summary
Population
Near-term and term infants with neonatal encephalopathy in low-middle income countries (5 studies, n= 348).
Intervention
Erythropoietin or one of its analogues.
Comparison
Placebo or usual care.
Outcome
Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later. Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56).
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Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies
Yang X, Yang B, Ming M, Li S, Wang F, Zhu Z, Ji C, Long J, Hu F, Xu Z, et al
Sleep medicine. 2019
Abstract
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.
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Iron supplementation for restless legs syndrome - A systematic review and meta-analysis
Avni T, Reich S, Lev N, Gafter-Gvili A
European journal of internal medicine. 2019
Abstract
BACKGROUND Iron supplementation, is recommended for the treatment of restless legs syndrome (RLS). We gathered evidence for the efficacy and safety of iron supplementation for RLS. METHODS A systematic review and meta-analysis of randomized controlled trials that compared iron supplementation versus no iron for patients with RLS was performed. Multiple databases were searched. The primary outcome was the effect of iron on the International Restless Legs Syndrome score (IRLSS) at 4weeks after treatment. For dichotomous data, risk ratios (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous data, weighted mean differences (WMD) were calculated. RESULTS Ten trials fulfilled the inclusion criteria. Iron therapy was associated with a significant decrease of the IRLSS of -3.55 [95% CI (-5.41) - (-1.68)] points and an increase in the percentage of patients with improvement of the IRLSS score, RR of 2.16 [95% CI 1.56-2.98]. IV FCM was associated with improvement in both the IRLSS (WMD of -2.79 (95% CI (-4.62) - (-0.96), 4 trials, I(2)=0%) and on the RLS-QOL by WMD of 8.67 (95% CI 1.68-15). Iron was associated with an increased rate of adverse events RR 2.04 (95% CI 1.46-2.85), which were not severe and not associated with increased rate of treatment discontinuation. CONCLUSION Iron supplementation is associated with improvement of the IRLSS score. Our meta-analysis supports the use of iron, oral or IV, as effective therapy for patients with RLS. Further studies should assess subgroups of patients most likely to benefit from iron supplementation.
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Colony stimulating factors (including erythropoietin, granulocyte colony stimulating factor and analogues) for stroke
Bath PM, Sprigg N, England T
Cochrane Database of Systematic Reviews. 2013;6:CD005207.
Abstract
BACKGROUND Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. CSFs have been shown to be neuroprotective in experimental stroke. OBJECTIVES To assess (1) the safety and efficacy of CSFs in people with acute or subacute ischaemic or haemorrhagic stroke, and (2) the effect of CSFs on circulating stem and blood cell counts. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (last searched September 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), MEDLINE (1985 to September 2012), EMBASE (1985 to September 2012) and Science Citation Index (1985 to September 2012). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted April 2012). We also searched reference lists of relevant articles and reviews. SELECTION CRITERIA We included randomised controlled trials recruiting people with acute or subacute ischaemic or haemorrhagic stroke. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF, CSF-1), thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome at the end of the trial. Secondary outcomes included safety at the end of treatment, death at the end of follow-up, infarct volume and haematology measures. DATA COLLECTION AND ANALYSIS Two review authors (TE and NS) independently extracted data and assessed trial quality. We contacted study authors for additional information. MAIN RESULTS We included a total of 11 studies involving 1275 participants. In three trials (n = 782), EPO therapy was associated with a significant increase in death by the end of the trial (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.19 to 3.3, P = 0.009) and a non-significant increase in serious adverse events. EPO significantly increased the red cell count with no effect on platelet or white cell count, or infarct volume. Two small trials of carbamylated EPO have been completed but have yet to be reported. We included eight small trials (n = 548) of G-CSF. G-CSF was associated with a non-significant reduction in early impairment (mean difference (MD) -0.4, 95% CI -1.82 to 1.01, P = 0.58) but had no effect on functional outcome at the end of the trial. G-CSF significantly elevated the white cell count and the CD34+ cell count, but had no effect on infarct volume. Further trials of G-CSF are ongoing. AUTHORS' CONCLUSIONS There are significant safety concerns regarding EPO therapy for stroke. It is too early to know whether other CSFs improve functional outcome.