The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Zhifei Dai - One of the best experts on this subject based on the ideXlab platform.
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Iron/dextran sulfate multilayered microcapsules for controlled release of 10-hydroxycamptothecin.
International journal of biological macromolecules, 2011Co-Authors: Shenglei Guo, Xiuli Yue, Jian Zheng, Yang Wang, Xiufeng Yan, Jing Dong, Na Guo, Lijia Jing, Zhifei DaiAbstract:Abstract Stable 10-hydroxycamptothecin (HCPT) microcrystals with a length of about 5–10 μm and a ζ -potential of −38.5 mV were produced by pH-induced reprecipitation in presence of a stabilizer hydroxypropylmethylcellulose. Sequential layer growth was achieved by the layer-by-layer (LbL) assembly of Fe 3+ and dextran sulfate (DS) on the surface of HCPT microcrystals via both electrostatic interaction and chemical complexation process. The satisfactory drug loading content (67.2 ± 0.82%) as well as high encapsulation efficiency (60.56 ± 0.82%) for four bilayers of Fe 3+ /DS coating was achieved. Both in vitro and in vivo release study revealed that the release time increased as the number of deposited Fe 3+ /DS bilayers increased. These results indicated that such Iron–Polysaccharide multilayered microcapsules can be a promising approach for the construction of an effective controlled release delivery system of HCPT as well as other drugs with potential cytotoxicity or short half-life time.
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Improved biocompatibility of thrombo-resistant Iron-Polysaccharides multilayer coatings on nitinols.
International journal of biological macromolecules, 2009Co-Authors: Meng Liu, Xiuli Yue, Zhengbao Zha, Zhifei DaiAbstract:Abstract Biocompatibility of two multilayer coatings of (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 was comparatively analyzed with respect to protein adsorption, leukocyte adhesion and cell–material interaction. Both of them showed significantly high albumin-to-fibrinogen adsorption ratio, suggesting good biocompatibility. Furthermore, the (Fe3+/DS/Fe3+/Hep)5 coating was found to exhibit the lowest non-specific protein adsorption due to the incorporation of dextran sulfate. Compared with uncoated Nitinol surfaces, Iron-Polysaccharide multilayer coating presented no deformation of leukocytes, indicating no signs of inflammatory reactions. Cell growth, cell adhesion and cell metabolic activity were all in good condition, verifying both (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 coatings had good cytocompatibility. Therefore, Iron-Polysaccharides multilayer coatings had greatly improved the biocompatibility of Nitinols.
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novel Iron Polysaccharide multilayered microcapsules for controlled insulin release
Acta Biomaterialia, 2009Co-Authors: Jian Zheng, Xiuli Yue, Zhifei Dai, Shaoqin Liu, Yang Wang, Xiufeng YanAbstract:Abstract Iron–Polysaccharide complexes have been extensively used for the treatment of Iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe3+ and dextran sulfate (DS) onto the surface of insulin microparticles. Fe3+ was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe3+/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe3+/DS)n multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56 ± 0.97% and drug loading content of 46.15 ± 0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe3+ as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.
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Novel Iron–Polysaccharide multilayered microcapsules for controlled insulin release
Acta biomaterialia, 2009Co-Authors: Jian Zheng, Xiuli Yue, Zhifei Dai, Shaoqin Liu, Yang Wang, Xiufeng YanAbstract:Abstract Iron–Polysaccharide complexes have been extensively used for the treatment of Iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe3+ and dextran sulfate (DS) onto the surface of insulin microparticles. Fe3+ was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe3+/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe3+/DS)n multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56 ± 0.97% and drug loading content of 46.15 ± 0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe3+ as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.
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Self-assembled hemocompatible coating on poly (vinyl chloride) surface
Applied Surface Science, 2009Co-Authors: Zhengbao Zha, Meng Liu, Xiuli Yue, Zhifei DaiAbstract:Abstract A stable hemocompatible coating was fabricated by consecutive alternating adsorption of Iron (III) and two kinds of Polysaccharides, heparin (Hep) and dextran sulfate (DS), onto poly (vinyl chloride) (PVC) surfaces via electrostatic interaction. The fluctuation of contact angles with the alternative deposition of Iron (III) and Polysaccharides verified the progressive buildup of the mulitilayer coating onto the PVC surface. Atomic force microscopy (AFM) analysis revealed that the PVC surfaces were completely masked by Iron–Polysaccharides multilayer coatings. The activated partial thromboplastin time (APTT) assay showed that both Hep/Fe 3+ /Hep and DS/Fe 3+ /Hep coated PVC were less thrombogenic than the uncoated one. Chromogenic assay for heparin activity proved definitively that the inhibition of locally produced thrombin was ascribed to the thromboresistance of the surface-bound heparin. Compared with the unmodified PVC surfaces, Iron–Polysaccharide multilayer coating presented a drastically reduced adhesion in vitro of platelets, polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC). Interestingly, the DS/Fe 3+ /Hep coating was found to exhibit higher hydrophilicity and stability, hence lower non-specific protein adsorption in comparison with Hep/Fe 3+ /Hep coating due to the incorporation of dextran sulfate into the multilayer coating.
Xiuli Yue - One of the best experts on this subject based on the ideXlab platform.
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Iron/dextran sulfate multilayered microcapsules for controlled release of 10-hydroxycamptothecin.
International journal of biological macromolecules, 2011Co-Authors: Shenglei Guo, Xiuli Yue, Jian Zheng, Yang Wang, Xiufeng Yan, Jing Dong, Na Guo, Lijia Jing, Zhifei DaiAbstract:Abstract Stable 10-hydroxycamptothecin (HCPT) microcrystals with a length of about 5–10 μm and a ζ -potential of −38.5 mV were produced by pH-induced reprecipitation in presence of a stabilizer hydroxypropylmethylcellulose. Sequential layer growth was achieved by the layer-by-layer (LbL) assembly of Fe 3+ and dextran sulfate (DS) on the surface of HCPT microcrystals via both electrostatic interaction and chemical complexation process. The satisfactory drug loading content (67.2 ± 0.82%) as well as high encapsulation efficiency (60.56 ± 0.82%) for four bilayers of Fe 3+ /DS coating was achieved. Both in vitro and in vivo release study revealed that the release time increased as the number of deposited Fe 3+ /DS bilayers increased. These results indicated that such Iron–Polysaccharide multilayered microcapsules can be a promising approach for the construction of an effective controlled release delivery system of HCPT as well as other drugs with potential cytotoxicity or short half-life time.
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Improved biocompatibility of thrombo-resistant Iron-Polysaccharides multilayer coatings on nitinols.
International journal of biological macromolecules, 2009Co-Authors: Meng Liu, Xiuli Yue, Zhengbao Zha, Zhifei DaiAbstract:Abstract Biocompatibility of two multilayer coatings of (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 was comparatively analyzed with respect to protein adsorption, leukocyte adhesion and cell–material interaction. Both of them showed significantly high albumin-to-fibrinogen adsorption ratio, suggesting good biocompatibility. Furthermore, the (Fe3+/DS/Fe3+/Hep)5 coating was found to exhibit the lowest non-specific protein adsorption due to the incorporation of dextran sulfate. Compared with uncoated Nitinol surfaces, Iron-Polysaccharide multilayer coating presented no deformation of leukocytes, indicating no signs of inflammatory reactions. Cell growth, cell adhesion and cell metabolic activity were all in good condition, verifying both (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 coatings had good cytocompatibility. Therefore, Iron-Polysaccharides multilayer coatings had greatly improved the biocompatibility of Nitinols.
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novel Iron Polysaccharide multilayered microcapsules for controlled insulin release
Acta Biomaterialia, 2009Co-Authors: Jian Zheng, Xiuli Yue, Zhifei Dai, Shaoqin Liu, Yang Wang, Xiufeng YanAbstract:Abstract Iron–Polysaccharide complexes have been extensively used for the treatment of Iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe3+ and dextran sulfate (DS) onto the surface of insulin microparticles. Fe3+ was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe3+/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe3+/DS)n multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56 ± 0.97% and drug loading content of 46.15 ± 0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe3+ as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.
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Novel Iron–Polysaccharide multilayered microcapsules for controlled insulin release
Acta biomaterialia, 2009Co-Authors: Jian Zheng, Xiuli Yue, Zhifei Dai, Shaoqin Liu, Yang Wang, Xiufeng YanAbstract:Abstract Iron–Polysaccharide complexes have been extensively used for the treatment of Iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe3+ and dextran sulfate (DS) onto the surface of insulin microparticles. Fe3+ was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe3+/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe3+/DS)n multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56 ± 0.97% and drug loading content of 46.15 ± 0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe3+ as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.
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Self-assembled hemocompatible coating on poly (vinyl chloride) surface
Applied Surface Science, 2009Co-Authors: Zhengbao Zha, Meng Liu, Xiuli Yue, Zhifei DaiAbstract:Abstract A stable hemocompatible coating was fabricated by consecutive alternating adsorption of Iron (III) and two kinds of Polysaccharides, heparin (Hep) and dextran sulfate (DS), onto poly (vinyl chloride) (PVC) surfaces via electrostatic interaction. The fluctuation of contact angles with the alternative deposition of Iron (III) and Polysaccharides verified the progressive buildup of the mulitilayer coating onto the PVC surface. Atomic force microscopy (AFM) analysis revealed that the PVC surfaces were completely masked by Iron–Polysaccharides multilayer coatings. The activated partial thromboplastin time (APTT) assay showed that both Hep/Fe 3+ /Hep and DS/Fe 3+ /Hep coated PVC were less thrombogenic than the uncoated one. Chromogenic assay for heparin activity proved definitively that the inhibition of locally produced thrombin was ascribed to the thromboresistance of the surface-bound heparin. Compared with the unmodified PVC surfaces, Iron–Polysaccharide multilayer coating presented a drastically reduced adhesion in vitro of platelets, polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC). Interestingly, the DS/Fe 3+ /Hep coating was found to exhibit higher hydrophilicity and stability, hence lower non-specific protein adsorption in comparison with Hep/Fe 3+ /Hep coating due to the incorporation of dextran sulfate into the multilayer coating.
Eugene Braunwald - One of the best experts on this subject based on the ideXlab platform.
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oral Iron therapy for heart failure with reduced ejection fraction design and rationale for oral Iron repletion effects on oxygen uptake in heart failure
Circulation-heart Failure, 2016Co-Authors: Gregory D Lewis, Marc J Semigran, Michael M Givertz, Rajeev Malhotra, Kevin J Anstrom, Adrian F Hernandez, Monica R Shah, Eugene BraunwaldAbstract:Iron deficiency is present in ≈50% of patients with heart failure and is an independent predictor of mortality. Despite growing recognition of the functional and prognostic significance of Iron deficiency, randomized multicenter trials exploring the use of oral Iron supplementation in heart failure, a therapy that is inexpensive, readily available, and safe, have not been performed. Moreover, patient characteristics that influence responsiveness to oral Iron in patients with heart failure have not been defined. Although results of intravenous Iron repletion trials have been promising, regularly treating patients with intravenous Iron products is both expensive and poses logistical challenges for outpatients. Herein, we describe the rationale for the Oral Iron Repletion effects on Oxygen Uptake in Heart Failure (IronOUT HF) trial. This National Institute of Health-sponsored trial will investigate oral Iron Polysaccharide compared with matching placebo with the primary end point of change in exercise capacity as measured by peak oxygen consumption at baseline and at 16 weeks. Clinical Trial Registration— URL: . Unique identifier: [NCT02188784][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02188784&atom=%2Fcirchf%2F9%2F5%2Fe000345.atom
George R. Buchanan - One of the best experts on this subject based on the ideXlab platform.
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Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.
JAMA, 2017Co-Authors: Jacquelyn M. Powers, George R. Buchanan, Leah Adix, Song Zhang, Ang Gao, Timothy L. MccavitAbstract:Importance Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral Iron despite Iron Polysaccharide complex possibly being better tolerated. Objective To compare the effect of ferrous sulfate with Iron Polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions Three mg/kg of elemental Iron once daily as either ferrous sulfate drops or Iron Polysaccharide complex drops for 12 weeks. Main Outcomes and Measures Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total Iron-binding capacity Results Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in Iron Polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (Iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL;P Conclusions and Relevance Among infants and children aged 9 to 48 months with nutritional Iron-deficiency anemia, ferrous sulfate compared with Iron Polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional Iron-deficiency anemia. Trial Registration clinicaltrials.gov Identifier:NCT01904864
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effect of low dose ferrous sulfate vs Iron Polysaccharide complex on hemoglobin concentration in young children with nutritional Iron deficiency anemia a randomized clinical trial
JAMA, 2017Co-Authors: Jacquelyn M. Powers, George R. Buchanan, Leah Adix, Song Zhang, Timothy L. MccavitAbstract:Importance Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral Iron despite Iron Polysaccharide complex possibly being better tolerated. Objective To compare the effect of ferrous sulfate with Iron Polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions Three mg/kg of elemental Iron once daily as either ferrous sulfate drops or Iron Polysaccharide complex drops for 12 weeks. Main Outcomes and Measures Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total Iron-binding capacity Results Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in Iron Polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (Iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (Iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P P P = .04). Conclusions and Relevance Among infants and children aged 9 to 48 months with nutritional Iron-deficiency anemia, ferrous sulfate compared with Iron Polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional Iron-deficiency anemia. Trial Registration clinicaltrials.gov Identifier:NCT01904864
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Low Dose Once Daily Oral Iron Treatment of Young Children with Nutritional Iron Deficiency Anemia
Blood, 2015Co-Authors: Jacquelyn M. Powers, Leah Adix, Timothy L. Mccavit, George R. BuchananAbstract:![Graphic][1] Background Iron deficiency anemia (IDA) is prevalent in young children whose diet includes prolonged breast feeding without Iron supplementation and/or excessive cow milk consumption. Oral Iron therapy is recommended to correct the anemia and reconstitute Iron stores, but few data exist to guide clinical decision-making. The recommended dosing of elemental Iron has been inconsistent in the literature, ranging from 2 to 6 mg/kg/day, given one to three times daily. To address the paucity of treatment data, the BESTIron study (Clinicaltrials.gov [NCT01904864][2]) was initiated to compare two liquid oral Iron agents (ferrous sulfate and NovaFerrum, an Iron Polysaccharide) using a once daily, low-dose regimen. Methods This study is a single center, double-blinded, randomized controlled superiority trial. Inclusion criteria include: age 9 months to 4 years with nutritional IDA by history and laboratory indices (Hgb 425 mg/dL). Exclusion criteria include: evidence of blood loss, malabsorption, other cause of anemia, prematurity (gestational age 11 g/dL, MCV >70 fl, Ret He >25 pg, serum ferritin >15 ng/mL, and TIBC
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low dose once daily oral Iron treatment of young children with nutritional Iron deficiency anemia
Blood, 2015Co-Authors: Jacquelyn M. Powers, Leah Adix, Timothy L. Mccavit, George R. BuchananAbstract:![Graphic][1] Background Iron deficiency anemia (IDA) is prevalent in young children whose diet includes prolonged breast feeding without Iron supplementation and/or excessive cow milk consumption. Oral Iron therapy is recommended to correct the anemia and reconstitute Iron stores, but few data exist to guide clinical decision-making. The recommended dosing of elemental Iron has been inconsistent in the literature, ranging from 2 to 6 mg/kg/day, given one to three times daily. To address the paucity of treatment data, the BESTIron study (Clinicaltrials.gov [NCT01904864][2]) was initiated to compare two liquid oral Iron agents (ferrous sulfate and NovaFerrum, an Iron Polysaccharide) using a once daily, low-dose regimen. Methods This study is a single center, double-blinded, randomized controlled superiority trial. Inclusion criteria include: age 9 months to 4 years with nutritional IDA by history and laboratory indices (Hgb 425 mg/dL). Exclusion criteria include: evidence of blood loss, malabsorption, other cause of anemia, prematurity (gestational age <30 weeks), major co-morbidity, adequate response to prior Iron therapy, or previous receipt of intravenous Iron. Upon enrollment, subjects are randomized 1:1 to either ferrous sulfate (15 mg/mL) or NovaFerrum (15 mg/mL) dosed at 3 mg/kg elemental Iron once daily at bedtime. Follow-up visits occur at 4, 8, and 12 weeks following study initiation. Definition of complete response at study exit is: Hgb >11 g/dL, MCV >70 fl, Ret He >25 pg, serum ferritin >15 ng/mL, and TIBC <425 mg/dL. The primary outcome, rate of change in hemoglobin concentration over 12 weeks, cannot yet be determined as enrollment is ongoing. Here we present the overall combined hematologic response to this "minimalist" treatment regimen for subjects who have completed the study to date. Results From 9/1/2013 to 8/1/2015, 72 patients (target accrual 80) enrolled in the study. Sixty-two subjects (56% male) completed it and are included in the analysis. Median age was 19 months (range 11 - 41 months). Subjects were predominantly Caucasian/White (Latino) (61%). Median baseline and week 12 laboratory values are shown in the Table. Thirteen patients received a transfusion for severe symptomatic anemia (median Hgb 3.6 g/dL, range 2.2 - 5.3 g/dL) prior to study entry. Forty-six of the 62 subjects (74%) completed all 3 study follow-up visits. Eleven subjects were lost to follow-up or discontinued study participation. Five others were considered treatment failures at 8 weeks (hemoglobin increment 8 g/dL) and received no further Iron therapy. Conclusion This analysis of children with nutritional IDA receiving a "patient-friendly" regimen of a single daily dose of 3 mg/kg elemental Iron for 12 weeks demonstrates a good hematologic response and suggests that higher doses of Iron therapy are not necessary to achieve resolution of anemia. While most subjects achieved a normal hemoglobin concentration, some required continued Iron therapy to assure repletion of Iron stores. Adverse effects ascribed to oral Iron treatment may result in part from prescribing higher or more frequent Iron doses, which may contribute to poor adherence and treatment failure. We acknowledge Gensavis Pharmaceuticals, LLC for their support of this investigator-initiated study. | | Baseline (N=62) Median (Range) | Week 12 (N=46) Median (Range) | | ------------------------------------------------------------------------------- | ---------------------------------------------- | --------------------------------------------- | | Hemoglobin concentration (g/dL) | 8.0 (4.4 - 10.6) | 11.9 (9.0 - 13.6) | | Mean cell volume (fl) | 59.9 (47.3 - 69.8) | 72.0 (54.7 - 81.9) | | Red cell distribution width (%) Baseline (n=56), Week 12 (n=46) | 21.1 (15.5 - 36.5) | 18.7 (12.5 - 26.4) | | Reticulocyte count (%) Baseline (n=60), Week 12 (n=45) | 1.4 (0.3 - 3.9) | 0.9 (0.4 - 1.8) | | Reticulocyte hemoglobin equivalent (pg) Baseline (n=41), Week 12 (n=40) | 17.2 (10.6 - 28.4) | 29.5 (15.9 - 34.3) | | Serum Iron (mcg/dL) | 20 (9 - 349) | 51 (15 - 394) | | Serum ferritin (ng/mL) | 2.5 (0.5 - 49.2) | 11 (2.4 - 46) | | Total Iron binding capacity (mg/dL) | 513 (236 - 636) | 394 (287 - 560) | Table 1. Median Laboratory Values at Baseline and Week 12 Disclosures Powers: Gensavis Pharmaceuticals, LLC: Research Funding. Mccavit: Gensavis Pharmaceuticals, LLC: Research Funding; Pfizer: Speakers Bureau; Novartis: Speakers Bureau. Adix: Gensavis Pharmaceuticals, LLC: Research Funding. Buchanan: Gensavis Pharmaceuticals, LLC: Research Funding. [1]: /embed/inline-graphic-2.gif [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01904864&atom=%2Fbloodjournal%2F126%2F23%2F2147.atom
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Deficiencies in the Management of Iron Deficiency Anemia During Childhood
Blood, 2011Co-Authors: Catherine Daniel, Ellen S. Plummer, George R. BuchananAbstract:Abstract 3154 Background: Iron deficiency anemia (IDA) is a common hematologic problem worldwide, potentially leading to cognitive delays, fatigue, seizures, and, when severe, high output heart failure. While IDA frequently is encountered in both the primary care setting and specialty clinics, its management is not evidence based. As a result, the diagnosis and treatment of IDA is often suboptimal. To help inform future clinical trials, we retrospectively characterized the clinical course of IDA in young patients (pts) referred to our center. Methods: Using our comprehensive hematology database, the records of children ≤ 18 years (yrs) of age with IDA seen in our outpatient clinic between January 1, 2006 and June 30, 2010 were identified and carefully reviewed. Results: Of 217 IDA pts in the database, 215 had evaluable records, 20 of whom were determined to have an alternative diagnosis. Of 195 evaluable pts, 64% were ≤4 yrs old at their first clinic visit and 31% were age 11–18 yrs. Pts ≤ age 4 yrs were 63% male and 60% Hispanic, whereas those age 11–18 yrs were 83% female and 37% Hispanic, 35% African-American, and 15% Caucasian. Causes of IDA in 128 pts ≤ 4 yrs were excessive consumption of cow milk (68%), breast feeding without Iron supplementation (13%), overall Iron-poor diet beyond 12 months (16%), prematurity (5%), and suspected malabsorption (6%). Causes of IDA in 60 pts aged 11–18 yrs were menorrhagia (43%), other blood loss (20%), Iron-poor diet (22%), and poor Iron absorption (7%). Some pts in both age groups had multiple causes of IDA, and in 17 the cause of the anemia was not clear. 129 pts (66%) were referred to us directly by their primary care physician (PCP), and 49 (25%) by the emergency department (ED), 37 of whom had been sent there by their PCP for evaluation of anemia. Prior to their first visit to our center, 115 pts (59%) had received at least one trial of Iron therapy, 62 with ferrous sulfate, 27 with carbonyl Iron, 5 with Iron Polysaccharide, and 15 with an Iron-containing multivitamin. For the pts ≤ 4 yrs of age where the precise dose of elemental Iron prescribed by the PCP was known (n=59), greater than half of the pts were prescribed doses of Iron outside of the accepted therapeutic range (3–6 mg/kg/day) (see figure). The pts9 mean Hb concentration before referral to our clinic (last recorded Hb measured either by the PCP or the ED) was 7.8 g/dl (n=170). Following evaluation in our hematology clinic, 86% of patients were treated with ferrous sulfate. However, 17% of such pts ≤ 4 yrs of age still received Iron doses outside of the accepted therapeutic range. At the time of their first and last visits to the hematology clinic the mean Hb values were 9.0 g/dl and 11.3 g/dl respectively. One third of pts had documented poor adherence with Iron therapy, due to poor tolerability (19%), gastrointestinal upset (11%), misunderstanding of prescribed dose (14%), and use of a lower dose than prescribed due to parental discretion (41%). 40% of pts were lost to follow up. Summary and Conclusions: Among pts referred for IDA to our academic specialty clinic, Hispanic male toddlers and Hispanic or African-American female adolescents were disproportionately represented. Most toddlers had nutritional IDA while most adolescents had menorrhagia. Pts often received sub-therapeutic doses of Iron before referral. After hematology clinic evaluation, most children demonstrated improvement of IDA; however, inappropriate dosing and non-adherence with oral Iron therapy were high, and many pts were lost to follow up. Insufficient screening and prevention of IDA remains problematic. Additionally, when IDA is suspected it is often inadequately treated or inappropriately referred to the ED or the hematology clinic, where treatment is associated with poor adherence and high attrition rates. Future research must focus on all of these deficiencies to prevent the many immediate and long-term sequelae of IDA. Disclosures: No relevant conflicts of interest to declare.
Jacquelyn M. Powers - One of the best experts on this subject based on the ideXlab platform.
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Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.
JAMA, 2017Co-Authors: Jacquelyn M. Powers, George R. Buchanan, Leah Adix, Song Zhang, Ang Gao, Timothy L. MccavitAbstract:Importance Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral Iron despite Iron Polysaccharide complex possibly being better tolerated. Objective To compare the effect of ferrous sulfate with Iron Polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions Three mg/kg of elemental Iron once daily as either ferrous sulfate drops or Iron Polysaccharide complex drops for 12 weeks. Main Outcomes and Measures Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total Iron-binding capacity Results Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in Iron Polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (Iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL;P Conclusions and Relevance Among infants and children aged 9 to 48 months with nutritional Iron-deficiency anemia, ferrous sulfate compared with Iron Polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional Iron-deficiency anemia. Trial Registration clinicaltrials.gov Identifier:NCT01904864
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effect of low dose ferrous sulfate vs Iron Polysaccharide complex on hemoglobin concentration in young children with nutritional Iron deficiency anemia a randomized clinical trial
JAMA, 2017Co-Authors: Jacquelyn M. Powers, George R. Buchanan, Leah Adix, Song Zhang, Timothy L. MccavitAbstract:Importance Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral Iron despite Iron Polysaccharide complex possibly being better tolerated. Objective To compare the effect of ferrous sulfate with Iron Polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions Three mg/kg of elemental Iron once daily as either ferrous sulfate drops or Iron Polysaccharide complex drops for 12 weeks. Main Outcomes and Measures Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total Iron-binding capacity Results Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in Iron Polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (Iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (Iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P P P = .04). Conclusions and Relevance Among infants and children aged 9 to 48 months with nutritional Iron-deficiency anemia, ferrous sulfate compared with Iron Polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional Iron-deficiency anemia. Trial Registration clinicaltrials.gov Identifier:NCT01904864
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Low Dose Once Daily Oral Iron Treatment of Young Children with Nutritional Iron Deficiency Anemia
Blood, 2015Co-Authors: Jacquelyn M. Powers, Leah Adix, Timothy L. Mccavit, George R. BuchananAbstract:![Graphic][1] Background Iron deficiency anemia (IDA) is prevalent in young children whose diet includes prolonged breast feeding without Iron supplementation and/or excessive cow milk consumption. Oral Iron therapy is recommended to correct the anemia and reconstitute Iron stores, but few data exist to guide clinical decision-making. The recommended dosing of elemental Iron has been inconsistent in the literature, ranging from 2 to 6 mg/kg/day, given one to three times daily. To address the paucity of treatment data, the BESTIron study (Clinicaltrials.gov [NCT01904864][2]) was initiated to compare two liquid oral Iron agents (ferrous sulfate and NovaFerrum, an Iron Polysaccharide) using a once daily, low-dose regimen. Methods This study is a single center, double-blinded, randomized controlled superiority trial. Inclusion criteria include: age 9 months to 4 years with nutritional IDA by history and laboratory indices (Hgb 425 mg/dL). Exclusion criteria include: evidence of blood loss, malabsorption, other cause of anemia, prematurity (gestational age 11 g/dL, MCV >70 fl, Ret He >25 pg, serum ferritin >15 ng/mL, and TIBC
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low dose once daily oral Iron treatment of young children with nutritional Iron deficiency anemia
Blood, 2015Co-Authors: Jacquelyn M. Powers, Leah Adix, Timothy L. Mccavit, George R. BuchananAbstract:![Graphic][1] Background Iron deficiency anemia (IDA) is prevalent in young children whose diet includes prolonged breast feeding without Iron supplementation and/or excessive cow milk consumption. Oral Iron therapy is recommended to correct the anemia and reconstitute Iron stores, but few data exist to guide clinical decision-making. The recommended dosing of elemental Iron has been inconsistent in the literature, ranging from 2 to 6 mg/kg/day, given one to three times daily. To address the paucity of treatment data, the BESTIron study (Clinicaltrials.gov [NCT01904864][2]) was initiated to compare two liquid oral Iron agents (ferrous sulfate and NovaFerrum, an Iron Polysaccharide) using a once daily, low-dose regimen. Methods This study is a single center, double-blinded, randomized controlled superiority trial. Inclusion criteria include: age 9 months to 4 years with nutritional IDA by history and laboratory indices (Hgb 425 mg/dL). Exclusion criteria include: evidence of blood loss, malabsorption, other cause of anemia, prematurity (gestational age <30 weeks), major co-morbidity, adequate response to prior Iron therapy, or previous receipt of intravenous Iron. Upon enrollment, subjects are randomized 1:1 to either ferrous sulfate (15 mg/mL) or NovaFerrum (15 mg/mL) dosed at 3 mg/kg elemental Iron once daily at bedtime. Follow-up visits occur at 4, 8, and 12 weeks following study initiation. Definition of complete response at study exit is: Hgb >11 g/dL, MCV >70 fl, Ret He >25 pg, serum ferritin >15 ng/mL, and TIBC <425 mg/dL. The primary outcome, rate of change in hemoglobin concentration over 12 weeks, cannot yet be determined as enrollment is ongoing. Here we present the overall combined hematologic response to this "minimalist" treatment regimen for subjects who have completed the study to date. Results From 9/1/2013 to 8/1/2015, 72 patients (target accrual 80) enrolled in the study. Sixty-two subjects (56% male) completed it and are included in the analysis. Median age was 19 months (range 11 - 41 months). Subjects were predominantly Caucasian/White (Latino) (61%). Median baseline and week 12 laboratory values are shown in the Table. Thirteen patients received a transfusion for severe symptomatic anemia (median Hgb 3.6 g/dL, range 2.2 - 5.3 g/dL) prior to study entry. Forty-six of the 62 subjects (74%) completed all 3 study follow-up visits. Eleven subjects were lost to follow-up or discontinued study participation. Five others were considered treatment failures at 8 weeks (hemoglobin increment 8 g/dL) and received no further Iron therapy. Conclusion This analysis of children with nutritional IDA receiving a "patient-friendly" regimen of a single daily dose of 3 mg/kg elemental Iron for 12 weeks demonstrates a good hematologic response and suggests that higher doses of Iron therapy are not necessary to achieve resolution of anemia. While most subjects achieved a normal hemoglobin concentration, some required continued Iron therapy to assure repletion of Iron stores. Adverse effects ascribed to oral Iron treatment may result in part from prescribing higher or more frequent Iron doses, which may contribute to poor adherence and treatment failure. We acknowledge Gensavis Pharmaceuticals, LLC for their support of this investigator-initiated study. | | Baseline (N=62) Median (Range) | Week 12 (N=46) Median (Range) | | ------------------------------------------------------------------------------- | ---------------------------------------------- | --------------------------------------------- | | Hemoglobin concentration (g/dL) | 8.0 (4.4 - 10.6) | 11.9 (9.0 - 13.6) | | Mean cell volume (fl) | 59.9 (47.3 - 69.8) | 72.0 (54.7 - 81.9) | | Red cell distribution width (%) Baseline (n=56), Week 12 (n=46) | 21.1 (15.5 - 36.5) | 18.7 (12.5 - 26.4) | | Reticulocyte count (%) Baseline (n=60), Week 12 (n=45) | 1.4 (0.3 - 3.9) | 0.9 (0.4 - 1.8) | | Reticulocyte hemoglobin equivalent (pg) Baseline (n=41), Week 12 (n=40) | 17.2 (10.6 - 28.4) | 29.5 (15.9 - 34.3) | | Serum Iron (mcg/dL) | 20 (9 - 349) | 51 (15 - 394) | | Serum ferritin (ng/mL) | 2.5 (0.5 - 49.2) | 11 (2.4 - 46) | | Total Iron binding capacity (mg/dL) | 513 (236 - 636) | 394 (287 - 560) | Table 1. Median Laboratory Values at Baseline and Week 12 Disclosures Powers: Gensavis Pharmaceuticals, LLC: Research Funding. Mccavit: Gensavis Pharmaceuticals, LLC: Research Funding; Pfizer: Speakers Bureau; Novartis: Speakers Bureau. Adix: Gensavis Pharmaceuticals, LLC: Research Funding. Buchanan: Gensavis Pharmaceuticals, LLC: Research Funding. [1]: /embed/inline-graphic-2.gif [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01904864&atom=%2Fbloodjournal%2F126%2F23%2F2147.atom
