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1.
Micronized, Microencapsulated Ferric Iron Supplementation in the Form of >Your< Iron Syrup Improves Hemoglobin and Ferritin Levels in Iron-Deficient Children: Double-Blind, Randomized Clinical Study of Efficacy and Safety.
Zečkanović, A, Kavčič, M, Prelog, T, Šmid, A, Jazbec, J
Nutrients. 2021;(4)
Abstract
A major problem of oral iron supplementation efficacy in children is its tolerability and compliance. We aimed to determine the safety and efficacy of a novel food supplement >Your< Iron Syrup in the replenishment of iron stores and improvement of hematological parameters in iron-deficient children aged nine months to six years. We randomized 94 healthy children with iron deficiency in a ratio of 3:1 to either receive >Your< Iron Syrup or placebo. A 12-week supplementation with >Your< Iron Syrup resulted in a significant increase in ferritin and hemoglobin levels as compared to placebo (p = 0.04 and p = 0.02). Adverse events were reported with similar frequencies across both study arms. >Your< Iron Syrup represents an effective, well-tolerated, and safe option for the management of nutritional iron deficiency in children.
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Optimizing patient expectations to improve therapeutic response to medical treatment: A randomized controlled trial of iron infusion therapy.
Akroyd, A, Gunn, KN, Rankin, S, Douglas, M, Kleinstäuber, M, Rief, W, Petrie, KJ
British journal of health psychology. 2020;(3):639-651
Abstract
OBJECTIVES Patient expectations have the ability to influence health outcomes and have been shown to play an important role as part of the placebo effect to influence the response to medical treatments. Increasing positive expectations have been proposed as an intervention to improve treatment response, although evidence for this to date is limited. We investigated whether a brief 10-min intervention directly targeting patient expectations prior to an iron infusion could enhance expectations and improve treatment response, in terms of patients' reported fatigue. DESIGN Randomized controlled trial. METHODS Forty-three patients diagnosed with iron deficiency anaemia were randomized to a brief expectation intervention or active control group prior to an intravenous iron infusion. Chalder Fatigue Scale scores were assessed prior to randomization and at one and four weeks. RESULTS The expectation intervention significantly improved patients' expectations about the effectiveness of the intravenous iron infusion, t(21) = -3.95, p = .001. While there were no significant differences between groups in fatigue at the one-week follow-up, fatigue was significantly lower in the intervention group at the four-week follow-up compared to the control group, F(1, 25) = 6.25, p = .019. This was largely influenced by a significant reduction in physical, as opposed to mental fatigue scores. CONCLUSIONS Boosting patients' positive expectations may be an effective way of enhancing patient response to treatment. In particular, targeting patient expectations with a brief intervention prior to medical treatments may result in a greater and longer therapeutic effect.
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Efficacy of processed amaranth-containing bread compared to maize bread on hemoglobin, anemia and iron deficiency anemia prevalence among two-to-five year-old anemic children in Southern Ethiopia: A cluster randomized controlled trial.
Orsango, AZ, Loha, E, Lindtjørn, B, Engebretsen, IMS
PloS one. 2020;(9):e0239192
Abstract
BACKGROUND Few studies have evaluated iron-rich plant-based foods, such as amaranth grain, to reduce anemia and iron deficiency anemia. Amaranth is rich in nutrients, but with high level of phytate. The objective of this trial was to evaluate the efficacy of home processed amaranth grain containing bread in the treatment of anemia, hemoglobin concentration and iron deficiency anemia among two-to-five year-old children in Southern Ethiopia. METHOD Children with anemia (hemoglobin concentration <110.0g/L) (N = 100) were identified by random sampling and enrolled in a 1:1 cluster randomized controlled trial for six months in 2017. The amaranth group (N = 50), received 150g bread containing 70% amaranth and 30% chickpea, the amaranth grain was processed at home (soaking, germinating, and fermenting) to decrease the phytate level. The maize group (N = 50), received 150g bread, containing processed maize (roasted and fermented) to give a similar color and structure with amaranth bread. Hemoglobin, ferritin, and CRP were measured at baseline and at the end of intervention. Hemoglobin and ferritin values were adjusted for altitude and infection, respectively. Generalized estimating equation and generalized linear model were used to analyze the data. RESULT In the last follow-up measure anemia prevalence was significantly lower in the amaranth group (32%) as compared with the maize group (56%) [adjusted risk ratios, aRR: 0.39 (95%CI: 0.16-0.77)]. Hemoglobin concentration estimate of beta coefficient was significantly higher in the amaranth group compared with the maize group [aβ 8.9g/L (95%CI: 3.5-14.3)], p-value <0.01. The risk of iron deficiency anemia is significantly lower in the amaranth group [aRR: 0.44 (95%CI: 0.23-0.83)] in the intention to treat analysis but not significant in the complete case analysis. There was no significant difference between groups in iron deficiency [aRR: 0.81 (95%CI: 0.55-1.19)]. CONCLUSION Processed amaranth bread had favorable effects on hemoglobin concentration and has the potential to minimize anemia prevalence. CLINICAL TRIAL REGISTRATION Trial registry number: PACTR201705002283263 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2283.
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4.
Iron Deficiency Anemia at Time of Vaccination Predicts Decreased Vaccine Response and Iron Supplementation at Time of Vaccination Increases Humoral Vaccine Response: A Birth Cohort Study and a Randomized Trial Follow-Up Study in Kenyan Infants.
Stoffel, NU, Uyoga, MA, Mutuku, FM, Frost, JN, Mwasi, E, Paganini, D, van der Klis, FRM, Malhotra, IJ, LaBeaud, AD, Ricci, C, et al
Frontiers in immunology. 2020;:1313
Abstract
Background: Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain. Methods: We performed two studies in southern coastal Kenya. In a birth cohort study, we followed infants to age 18 mo and assessed whether anemia or iron deficiency at time of vaccination predicted vaccine response to three-valent oral polio, diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine, ten-valent pneumococcal-conjugate vaccine and measles vaccine. Primary outcomes were anti-vaccine-IgG and seroconversion at age 24 wk and 18 mo. In a randomized trial cohort follow-up, children received a micronutrient powder (MNP) with 5 mg iron daily or a MNP without iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were anti-measles IgG, seroconversion and avidity at age 11.5 mo and 4.5 y. Findings: In the birth cohort study, 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometric indices and maternal antibodies, hemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis-IgG at 24 wk (p = 0.0071, p = 0.0339) and 18 mo (p = 0.0182, p = 0.0360); (B) anti-pertussis filamentous hemagglutinin-IgG at 24 wk (p = 0.0423); and (C) anti-pneumococcus 19 IgG at 18 mo (p = 0.0129). Anemia and serum transferrin receptor at time of vaccination were the strongest predictors of seroconversion against diphtheria (p = 0.0484, p = 0.0439) and pneumococcus 19 at 18 mo (p = 0.0199, p = 0.0327). In the randomized trial, 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5 y. Compared to infants that did not receive iron, those who received iron at time of vaccination had higher anti-measles-IgG (p = 0.0415), seroconversion (p = 0.0531) and IgG avidity (p = 0.0425) at 11.5 mo. Interpretation: In Kenyan infants, anemia and iron deficiency at time of vaccination predict decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine may be increased by iron supplementation at time of vaccination. These findings argue that correction of iron deficiency during early infancy may improve vaccine response.
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Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.
Ponikowski, P, Kirwan, BA, Anker, SD, McDonagh, T, Dorobantu, M, Drozdz, J, Fabien, V, Filippatos, G, Göhring, UM, Keren, A, et al
Lancet (London, England). 2020;(10266):1895-1904
Abstract
BACKGROUND Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 μg/L, or 100-299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING Vifor Pharma.
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High-dose intravenous versus oral iron in blood donors with iron deficiency: The IronWoMan randomized, controlled clinical trial.
Drexler, C, Macher, S, Lindenau, I, Holter, M, Moritz, M, Stojakovic, T, Pieber, TR, Schlenke, P, Amrein, K
Clinical nutrition (Edinburgh, Scotland). 2020;(3):737-745
Abstract
INTRODUCTION Frequent blood donation often leads to iron deficiency and even anemia but appropriate strategies for detection and prevention are currently not mandatory. At the Medical University of Graz, we conducted a single-center prospective clinical trial to compare oral and IV iron supplementation in iron deficient blood donors including Austrian regular whole blood and platelet apheresis donors. We aimed to determine the difference of transferrin saturation between the treatment groups 8-12 weeks iron administration besides other parameters of iron status and blood count. METHODS 176 healthy male and female blood donors with iron deficiency (ferritin ≤30 ng/mL) were randomized to either a single dose of IV ferric carboxymaltose (1000 mg, n = 86) or oral iron (II)fumarate (100 tablets of 100 mg [10 per week], n = 90). RESULTS Between 2014 and 2016, 172 donors (137 women) completed the study; 4 in the oral group were lost to follow-up. At follow-up, median (IQR) transferrin saturation and ferritin were significantly higher in the intravenous group (27 [23-35]%, vs 21.0 [16-32]%; p < 0.001 and 105 [75-145] ng/mL vs 25 [17-34] ng/mL; p < 0.001, respectively) while median (IQR) hemoglobin levels were comparable (IV, 13.6 [13.0-14.4] g/dL vs oral, 13.6 [13.0-14.2] g/dL). The frequency of adverse effects was comparable (38% in both groups) and no serious adverse events occurred. CONCLUSIONS A single dose of 1000 mg of intravenous iron is highly effective to counteract iatrogenic iron deficiency in blood donors. Oral iron appears to be an acceptable alternative. The assessment of body iron stores should play a key role in maintaining blood donors' health. This trial was registered at www.clinicaltrials.gov as NCT01787526 on February 8, 2013 and at www.clinicaltrialsregister.eu (EudraCT identifier: 2013-000327-14) on September 24, 2013.
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Is Iron Supplementation Influenced by Sub-Clinical Inflammation?: A Randomized Controlled Trial Among Adolescent Schoolgirls in Myanmar.
Htet, MK, Fahmida, U, Dillon, D, Akib, A, Utomo, B, Thurnham, DI
Nutrients. 2019;(4)
Abstract
Iron absorption was impaired in the presence of sub-clinical inflammation (SCI) and might hamper the effect of iron supplementation. The purpose of the study was to identify the influence of SCI on iron supplementation. A randomized, double-blinded, placebo-controlled experimental study was conducted among anaemic adolescent schoolgirls in Ayeyarwady region, Myanmar. A total of 402 schoolgirls were recruited from six schools screened from 1269 girls who were assigned into one of four groups: Folate group (2.5 mg of folate), Vitamin A group (15,000 IU of vitamin), Iron folate group (60 mg elemental iron and folate) and Iron, and vitamin A and folate group. Supplementation was done once a week for 12 weeks. Iron, vitamin A and inflammation were measured at the baseline, middle and endline. Changes in serum ferritin and body iron were significantly higher in the IFA and IFA + vitA among those without SCI. There was interaction between vitamin A and SCI on Hb changes. Analysis of GLM repeated measure showed interactions between treatment and SCI for hemoglobin and serum transferrin receptor. Those treated with vitamin A had better outcomes when there was SCI. Inflammation accompanied a negative effect on iron supplementation and vitamin A improved efficacy of iron supplementation in the presence of SCI.
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Comparison of ferrous sulfate, polymaltose complex and iron-zinc in iron deficiency anemia.
Ozsurekci, Y, Unal, S, Cetin, M, Gumruk, F
Minerva pediatrica. 2019;(5):449-454
Abstract
BACKGROUND The purpose of this study was to compare the effectiveness of different oral iron preparations in children with iron deficiency anemia (IDA). METHODS Sixty children with IDA, aged between 6 months and 180 months, were randomly assigned into three treatment groups. Group I included children with IDA who received ferrous sulfate (Fe-S); Group II included children receiving iron polymaltose complexes (Fe-OH-PM), and Group III included children receiving a single preparation of combined iron and zinc (Fe-Zn). The effect of different iron preparations were evaluated and compared. The duration of treatment was 8 weeks. Hemoglobin (Hgb) levels, as well as other hematological parameters were determined at admission and the first, fourth, and eighth weeks of the treatment. RESULTS The Hgb levels of patients in all three groups were statistically higher in the fourth (P=0.001) and eighth (P<0.001) weeks compared to baseline; although there was no difference between the groups at the end of the treatment period (P>0.05). CONCLUSIONS Our results indicate that, Fe-OH-PM and Fe-Zn preparations may also be preferred as a choice like Fe-S for treatment of children with IDA.
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Randomized trial of intravenous iron-induced hypophosphatemia.
Wolf, M, Chertow, GM, Macdougall, IC, Kaper, R, Krop, J, Strauss, W
JCI insight. 2018;(23)
Abstract
BACKGROUND Hypophosphatemia can complicate intravenous iron therapy, but no head-to-head trials compared the effects of newer intravenous iron formulations on risks and mediators of hypophosphatemia. METHODS In a randomized, double-blinded, controlled trial of adults with iron deficiency anemia from February 2016 to January 2017, we compared rates of hypophosphatemia in response to a single FDA-approved course of ferric carboxymaltose (n = 1,000) or ferumoxytol (n = 997). To investigate pathophysiological mediators of intravenous iron-induced hypophosphatemia, we nested within the parent trial a physiological substudy (ferric carboxymaltose, n = 98; ferumoxytol, n = 87) in which we measured fibroblast growth factor 23 (FGF23), calcitriol, and parathyroid hormone (PTH) at baseline and 1, 2, and 5 weeks later. RESULTS The incidence of hypophosphatemia was significantly higher in the ferric carboxymaltose versus the ferumoxytol group (<2.0 mg/dl, 50.8% vs. 0.9%; <1.3 mg/dl, 10.0% vs. 0.0%; P < 0.001), and hypophosphatemia persisted through the end of the 5-week study period in 29.1% of ferric carboxymaltose-treated patients versus none of the ferumoxytol-treated patients (P < 0.001). Ferric carboxymaltose, but not ferumoxytol, increased circulating concentrations of biologically active FGF23 (mean within-patient percentage change from baseline to week 2 peak: +302.8 ± 326.2% vs. +10.1 ± 61.0%; P < 0.001), which was significantly associated with contemporaneous hypophosphatemia, renal phosphate wasting, and decreased serum calcitriol and calcium, and increased PTH concentrations. CONCLUSIONS Ferric carboxymaltose rapidly increases biologically active FGF23 in patients with iron deficiency anemia. Paralleling hereditary and other acquired syndromes of hypophosphatemic rickets/osteomalacia, ferric carboxymaltose-induced FGF23 elevation triggers a pathophysiological cascade of renal phosphate wasting, calcitriol deficiency, and secondary hyperparathyroidism that frequently culminates in hypophosphatemia. TRIAL REGISTRATION ClinicalTrials.gov, NCT02694978FUNDING. AMAG Pharmaceuticals, Inc.Role of the funding source: This study was supported by AMAG Pharmaceuticals, Inc. The academic investigators designed the clinical trial, performed the analyses, and authored the manuscript with input from the coauthors from AMAG Pharmaceuticals, Inc.
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Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial.
Matias, SL, Mridha, MK, Young, RT, Khan, MSA, Siddiqui, Z, Ullah, MB, Vosti, SA, Dewey, KG
The Journal of nutrition. 2018;(7):1167-1176
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Abstract
BACKGROUND Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among young children are public health concerns in developing countries. OBJECTIVE We evaluated the effects of small-quantity lipid-based nutrient supplements (LNSs) and micronutrient powder (MNP) on anemia, ID, and IDA in 18-mo-old Bangladeshi children. METHODS We enrolled 4011 pregnant women in a cluster-randomized effectiveness trial with 4 arms-1) LNS-LNS: LNSs (including 20 mg Fe) for women daily during pregnancy and 6 mo postpartum and LNSs (including 9 mg Fe) for children daily from 6 to 24 mo of age (LNS-C); 2) IFA-LNS: iron (60 mg) and folic acid (IFA) for women daily during pregnancy and every other day for 3 mo postpartum and LNS-C for children; 3) IFA-MNP: IFA for women, and MNP (including 10 mg Fe) for children daily from 6 to 24 mo; and 4) IFA-Control: IFA for women and no child supplement. Hemoglobin, serum ferritin, and soluble transferrin receptor (sTfR) were assessed in a subsample of children (n = 1121) at 18 mo to identify anemia (hemoglobin <110g/L), ID (ferritin <12 µg/L or sTfR >8.3 mg/L), and IDA. Data were analyzed with the use of mixed-effects modeling. RESULTS Compared with the IFA-Control arm, hemoglobin was higher in the LNS-LNS and IFA-LNS arms and ferritin was higher and sTfR was lower in the LNS-LNS, IFA-LNS, and IFA-MNP arms; LNS-LNS children had reduced odds of anemia (OR: 0.46; 95% CI: 0.25, 0.84), high sTfR (OR: 0.47; 95% CI: 0.29, 0.73), and ID (OR: 0.45; 95% CI: 0.28, 0.71); and all 3 groups had lower odds of low ferritin [corrected for inflammation; OR (95% CI)-LNS-LNS: 0.29 (0.13, 0.63); IFA-LNS: 0.25 (0.11, 0.59); and IFA-MNP: 0.37 (0.18, 0.76)] and IDA [LNS-LNS: 0.35 (0.18, 0.67); IFA-LNS: 0.45 (0.24,0.85); and IFA-MNP: 0.47 (0.26, 0.87)]. CONCLUSIONS Home fortification using LNSs or MNP reduced IDA in 18-mo-old Bangladeshi children. The provision of LNSs in both pregnancy and childhood also reduced child anemia and ID. These findings are relevant to programs targeting similar populations. This trial was registered at www.clinicaltrials.gov as NCT01715038.