Enhancing 7-dehydrocholesterol suppresses brain ferroptosis and tissue injury after neonatal hypoxia-ischemia.

Neonatal hypoxic-ischemic brain injury (HIBI) results in part from excess reactive oxygen species and iron-dependent lipid peroxidation (i.e. ferroptosis). The vitamin D precursor 7-dehydrocholesterol (7-DHC) may inhibit iron-dependent lipid peroxidation. Primary neurons underwent oxygen and glucose deprivation (OGD) injury and treatment with 7-DHC-elevating medications such as cariprazine (CAR) or vehicle. Postnatal day 9 mice underwent sham surgery or carotid artery ligation and hypoxia and received intraperitoneal CAR. In neurons, CAR administration resulted in significantly increased cell survival compared to vehicle controls, whether administered 48 h prior to or 30 min after OGD, and was associated with increased 7-DHC. In the mouse model, malondialdehyde and infarct area significantly increased after HIBI in the vehicle group, which were attenuated by post-treatment with CAR and were negatively correlated with tissue 7-DHC concentrations. Elevating 7-DHC concentrations with CAR was associated with improved cellular and tissue viability after hypoxic-ischemic injury, suggesting a novel therapeutic avenue.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

The magnitude of the plasma hepcidin response to oral iron supplements depends on the iron dosage.

BACKGROUND: Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. METHODS: Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. RESULTS: Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9; p < 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2 = 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2 = 0.529, p = 0.002). CONCLUSION: We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

Immediate postpartum anemia and associated factors at shewarobit health facilities, Amhara, Ethiopia, 2022: a cross sectional study.

BACKGROUND: Immediate postpartum anemia occurs when the amount of red blood cell count is reduced or hemoglobin concentration is below 10 g/dl in the immediate postpartum. It occurs primarily due to inadequate iron intake before and during pregnancy and blood loss during delivery. The aim of this study is to assess the proportion of immediate postpartum anemia and associated factors among mothers who gave birth at Shewarobit health facilities; in Amhara, Ethiopia. METHODS: Institutional-based cross-sectional study was conducted from June to September 2022. A systematic random sampling method was employed to select the study participants. The data were collected through interviewer-assisted questions. Data were entered into Epi Data software version 4.6.0.4 and exported to SPSS 21 for analysis, and descriptive statistics were computed. Logistic regression was applied, and P-values less than 0.05 were considered statistically significant. RESULTS: This study was conducted among 307 study participants and, the proportion of immediate postpartum anemia was 41.4% [95% CI: 36.7-46.6]. Having postpartum hemorrhage [AOR = 4.76, 95% CI: 2.44-9.28], not taking iron and folic acid supplementation [AOR = 6.19, 95% CI: 2.69, 14.22], having a prolonged second stage of labor [AOR = 2.52, 95% CI: 1.16-5.44], and mid-upper arm circumference < 23 cm [AOR = 2.02, 95% CI: 1.11-3.68] were factors significantly associated with immediate postpartum anemia. CONCLUSIONS: The proportion of immediate postpartum anemia was public problem in Shewarobit health facilities. Following the progress of labor using a partograph, closely monitoring and immediate intervention of PPH, and prevent undernutrition during antenatal care is recommended.

Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

BACKGROUND OBJECTIVES: Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. METHODS: The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. RESULTS: A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. INTERPRETATION CONCLUSIONS: Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.

Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

BACKGROUND: NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. METHODS: A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. RESULTS: A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). CONCLUSIONS: Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

Should echocardiogram be undertaken routinely when a child has severe iron deficiency anaemia?

Iron deficiency anaemia (IDA) is common in children. Treatment usually consists of oral iron therapy and, if severe, inpatient hospitalisation with blood transfusion. Providers may also undertake an echocardiogram, depending on availability and the severity of anaemia. A male toddler with nutritional IDA, haemoglobin of 1.7 g/dL (the lowest level in the literature) and hypertension had left ventricular hypertrophy (LVH) on the initial echocardiogram. He was managed acutely with judicious blood transfusion, followed by oral iron supplementation and anti-hypertensive medication at discharge. Repeat echocardiogram a month later demonstrated slight improvement of the LVH but the hypertension persisted at follow-up 6 months later. There was complete resolution of the findings a year later. In chronic nutritional IDA, there can be structural cardiac changes which can affect the acute management and requires close follow-up. It is important to use echocardiography in such severe cases.Abbreviations: CHF: congestive heart failure; CM: cardiomyopathy; DCM: dilated cardiomyopathy; ICU: intensive care unit; IDA: iron deficiency anaemia; IVSd: interventricular septum in diastole; LA: left atrium; LV: left ventricle; LVEDD: left ventricular end-diastolic diameter; LVH: left ventricular hypertrophy; LVM: left ventricular mass; LVPWd: left ventricular posterior wall end-diastole; PRBC: packed red blood cells.

Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence.

PURPOSE OF REVIEW: Iron deficiency is common in patients with heart failure, affecting up to half of ambulatory patients and an even greater percentage of patients admitted for acute decompensation. Iron deficiency in this population is also associated with poor outcomes, including worse quality of life in addition to increased hospitalizations for heart failure and mortality. Evidence suggests that patients with iron deficiency in heart failure may benefit from repletion with IV iron. RECENT FINDINGS: In this review, we outline the etiology and pathophysiology of iron deficiency in heart failure as well as various iron formulations available. We discuss evidence for intravenous iron repletion with a particular focus on recent studies that have evaluated its effects on hospitalizations and mortality. Finally, we discuss areas of uncertainty and future study and provide practical guidance for iron repletion. SUMMARY: In summary, there is overwhelming evidence that intravenous iron repletion in patients with iron deficiency in heart failure is both beneficial and safe. However, further evidence is needed to better identify which patients would most benefit from iron repletion as well as the ideal repletion strategy.

Executive summary of the consensus document on the management of perioperative anemia in Spain.

Perioperative anemia is an independent risk factor for postoperative morbidity and mortality. However, conceptual, logistical and administrative barriers persist that hinder the widespread implementation of protocols for their management. The project coordinator convened a multidisciplinary group of 8 experienced professionals to develop perioperative anemia management algorithms, based on a series of key points (KPs) related to its prevalence, consequences, diagnosis and treatment. These KPs were assessed using a 5-point Likert scale, from "strongly disagree [1]" to "strongly agree [5]". For each KP, consensus was reached when receiving a score of 4 or 5 from at least 7 participants (>75%). Based on the 36 KPs agreed upon, diagnostic-therapeutic algorithms were developed that we believe can facilitate the implementation of programs for early identification and adequate management of perioperative anemia, adapted to the characteristics of the different institutions in our country.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase 3 Roxadustat Trials in Japan.

INTRODUCTION: Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. METHODS: Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. RESULTS: Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36-37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52-25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23-15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07-33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82-33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< - 2 fL; adjusted OR 5.55; 95% CI 1.73-17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. CONCLUSION: In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. TRIAL REGISTRATION: NCT02780726, NCT02952092, NCT02780141, NCT02779764.

Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat.

Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent ß-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial.

INTRODUCTION: Despite the improvement in medical management, many patients with transfusion-dependent ß-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent ß-thalassaemia with very high iron overload. METHODS AND ANALYSIS: This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent ß-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER: The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).

Current concepts in postpartum anemia management.

PURPOSE OF REVIEW: Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. RECENT FINDINGS: Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. SUMMARY: Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

Association between Iron-Folic Acid Supplementation during Pregnancy and Maternal and Infant Anemia in West Java, Indonesia: A Mixed-Method Prospective Cohort Study.

The Indonesian government has provided iron-folic acid (IFA) supplementation in response to maternal pregnancy iron-deficiency anemia. However, community-based cohorts on IFA's effects on maternal and infant anemia are limited. A mixed-method study design with a primary longitudinal cohort was used to observe the association between IFA and anemia in mothers and infants. Iron-folic acid supplementation was observed throughout pregnancy. Anemia status was based on a single hemoglobin assessment using HemoCue Hb 201 + in the second or third trimester of pregnancy for the mother and at birth for the infant. Qualitative data were collected via in-depth interviews (IDIs) and a forum group discussion (FGD). Iron-folic acid supplementation with > 180 tablets throughout pregnancy was associated with lower pregnancy anemia (adjusted relative risk [aRR] = 0.25, 95% CI: 0.092-0.664, P = 0.006) after adjusting for potential confounding variables. Supplementation with IFA was not associated with infant anemia (RR = 1.033, 95% CI: 0.70-1.54, P = 0.873 for 90-180 tablets and RR = 1.07, 95% CI 0.70-1.63, P = 0.774 for > 180 tablets). The IDIs and FGD suggested that IFA and multivitamin content knowledge, IFA consumption monitoring, and paternal involvement were important in IFA supplementation and effectiveness in reducing anemia. Iron-folic acid supplementation was associated with reduced maternal but not infant anemia. Because maternal anemia is associated with infant anemia, an anemia monitoring program for women in early pregnancy is vital in addressing infant health. Paternal involvement was also identified as a major factor in maternal and child health.