Management Of Anemia In Patients Research Articles

Peripheral blood cytopenia before treatment in HCV patients: is it a limitation for HCV treatment in the era of DAA?

Peripheral blood cytopenia before treatment in <scp>HCV</scp> patients: is it a limitation for <scp>HCV</scp> treatment in the era of <scp>DAA</scp>?

Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis

Objective:To determine whether Medicare’s decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time.Methods:The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses.Results:Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses.Limitations:This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature.Conclusions:This study indicates that Medicare’s coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.

Anemia Management in Patients Receiving Chronic Hemodialysis

Anemia treatment in hemodialysis-dependent (HDD) CKD patients involves adequate supply of iron and an erythropoiesis-stimulating agent (ESA). Despite widespread usage of these agents, there is no generally accepted "standard dosing algorithm" for treating anemia in HDD-CKD patients. The new anemia Quality Incentive Program (QIP) introduced by the Centers for Medicare & Medicaid Services represents a motivation to standardize and harmonize iron and ESA regimens with interactive electronic algorithms and novel modes of deliveries for IV iron and ESA doses. In addition, quality assessment and performance improvement programs at dialysis facilities include achieving measurable improvement in health outcomes, healthcare cost, and reductions in medical errors. Thus, the Corporate Medical Advisory Board for Fresenius Medical Services (FMS) is evaluating an anemia algorithm that will be incorporated into the automated workflow of a new clinical system at FMS clinics. In the future, such systems might communicate with medication pumps incorporated into state-of-the-art HD machines, thereby eliminating manual data entry of medication orders and other potential errors related to data entry or administration of medications such as ESA and IV iron. In addition, the CritLine III TQA Monitor, which allows real-time blood volume, oxygen, and anemia monitoring during HD in acute and chronic settings, may become an integrated diagnostic tool to improve volume and anemia management through better fluid management and ESA dose adjustment algorithms. These novel interactive electronic algorithms, delivery and monitoring methods, and data transfer may be integrated in the Pharmatech process to meet patient-specific anemia therapy.

Treatment of anemia in chronic kidney disease: known, unknown, and both

Erythropoiesis is a rapidly evolving research arena and several mechanistic insights show therapeutic promise. In contrast with the rapid advance of mechanistic science, optimal management of anemia in patients with chronic kidney disease remains a difficult and polarizing issue. Although several large hemoglobin target trials have been performed, optimal treatment targets remain elusive, because none of the large trials to date have unequivocally identified differences in primary outcome rates or death rates, and because other reported outcomes indicate the potential for harm (rates of stroke, early requirement for dialysis, and vascular access thrombosis) and benefit (reductions in transfusion requirements and fatigue).

Iron overdose: a contributor to adverse outcomes in randomized trials of anemia correction in CKD

Administration of intravenous iron to supplement erythropoiesis stimulating agents (ESAs) has become a common practice in the management of anemia in patients with end-stage renal disease. Randomized clinical trials of anemia correction in this population have shown more adverse outcomes in CKD and ESRD patients assigned to the higher hemoglobin targets. Retrospective analysis of these trials suggests that morbidity is higher in subjects who fail to achieve the designated hemoglobin target and are typically exposed to higher doses of ESAs and iron than those that easily achieve the intended targets. Intravenous iron administration circumvents the natural biologic mechanisms for handling and utilization of iron. There is in vitro and in vivo evidence that intravenous iron preparations can cause oxidative stress, endothelial dysfunction, inflammation, impaired immunity, and renal injury. Since iron overload is known to promote endothelial dysfunction, cardiovascular disease, and immune dysfunction which are the leading causes of premature mortality in CKD and ESRD patients, it is imperative to exercise caution with the use of IV iron preparations in this population. The present review is intended to provide a brief overview of the potential adverse effects of the overzealous use of these agents.

Current Practice of Anemia Management in Patients With Inflammatory Bowel Disease Across Four European Countries

Current Practice of Anemia Management in Patients With Inflammatory Bowel Disease Across Four European Countries

The D&amp;T Report

The D&amp;T Report

Erythropoietic therapy: time for some changes

Iain Macdougall gives an overview of four key randomized controlled trials (RCTs) that have formed and changed anaemia management in patients with chronic kidney disease (CKD). He looks at the implications of these findings and their impact on current and future best renal practice.

Insights and Perspectives in the Clinical and Operational Management of Cancer-Related Anemia

Management of anemia in patients with cancer presents challenges from clinical, operational, and economic perspectives. Clinically, anemia in these patients may result from treatment (chemotherapy, radiation therapy, or surgical interventions) or from the malignancy itself. Anemia not only contributes to cancer-related fatigue and other quality of life issues, but also affects prognosis. From the operational perspective, a patient with cancer who is also anemic may consume more laboratory, pharmacy, and clinical resources than other patients with cancer.

Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

BackgroundAnemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.Methods/DesignThis is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.DiscussionThe C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.Trial registrationClinicaltrials.gov NCT00827021

Funding for Medical Education: Maintaining a Healthy Separation From Industry

Attitudes and policies about conflict of interest in medical education have evolved rapidly in the last several years. Temporally and conceptually, these changes have paralleled the rise of the relatively new field of behavioral economics in explaining commercial relationships. The traditional view of economics holds that in any transaction, all inputs and outcomes are simply the result of decisions by rational participants making choices that optimize their goals; however, the past decades have seen a reassessment of this “expected utility theory” with the growing awareness that unconscious biases and emotional factors profoundly affect behavior.1 The same insight has begun to influence how we think about medical education and the messages that are sent by and received from industry-sponsored speakers and programs. Because cardiology addresses the most common illnesses in developed societies and employs the most widely used and costly drugs and devices, these issues have been especially acute in this field. Response by Harrington and Califf see p 2228 Unquestionably, the drug and device industries make important contributions to the development of products that reduce the morbidity and mortality of cardiovascular disease. Industry is also a major source of both funding for and collaboration in cardiology research, and it provides substantial support for professional cardiology societies, topics that are beyond the scope of this report. But in the realm of teaching, whether of medical students, house officers, or practitioners, there is growing concern that educational activities should not be supported or influenced by companies whose profitability and very existence depend on the sales volume of the products they make.2 Our position that industry should not directly support educational programs is not ideologically driven. Rather, it is based on the expectation that medical knowledge can be transferred most efficiently and with the least distortion if those responsible for this …

Prevalence and management of anemia in patients with non-myeloid tumors undergoing systemic therapy.

e19658 Background: The European Cancer Anemia Survey revealed that, despite a high prevalence of anemia (hemoglobin (Hb)<12 g/dL) in cancer patients (pts) undergoing chemotherapy (CT), few receive treatment. The present study aimed to provide data on anemia prevalence and management in Spain. Methods: Observational, cross-sectional study performed in 2008 in 21 Spanish hospitals. Eligible pts were ≥18 years, with non-myeloid malignancies and treated with systemic therapy (CT, hormonal therapy (HT) or immunotherapy (IT)). Data on clinical characteristics, cancer and anemia therapy, and Hb levels were collected at inclusion and for the previous 4 weeks. Anemia was defined as Hb<12 g/dL. Results: The study included 214 pts with a median age of 63 years (range 20-91), 58% women, 73% with solid tumors, and 79% with advanced disease. CT was used in 91% of pts (of whom 26% received platinum compounds), HT in 8.5%, and IT in 8.5%. Median Hb levels were 12 g/dL (7.4-16.1), with 48% (95% confidence interval: 45-59) of pts presenting anemia (of whom 13% were <10 g/dL and 31% were symptomatic). There was a trend towards higher prevalence of anemia in women (52% vs 42%, p=0.14) and in solid tumors (52% vs 37%, p= 0.09). No association was found between anemia and age, tumor stage or type, nor cancer therapy type. A higher prevalence was observed in pts with CT (51% vs 20%, p=0,01), platinum-based CT (70% vs 47%, p=0.01) or palliative CT (61% vs 39%, p=0.003). The use of anemia treatments in the last 4 weeks in pts with anemia was as follows: 62% did not receive any treatment, 24% received ESAs, 14% received iron supplementation and 8.7% received transfusion. Conclusions: In the Spanish hospital setting, approximately half of pts with non-myeloid tumors undergoing systemic therapy suffer anemia. Our analysis indicates that more than fifty percent of anemic pts do not receive treatment. Study supported with an educational grant of AMGEN S.A. No significant financial relationships to disclose.

Canadian Society of Nephrology Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

Canadian Society of Nephrology Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD

Anemia is prevalent in patients with chronic kidney disease (CKD) and is associated with lower quality of life and higher risk of adverse outcomes, including cardiovascular disease and death. Anemia management in patients with CKD currently revolves around the use of erythropoiesis-stimulating agents and supplemental iron. However, many patients do not respond adequately and/or require high doses of these medications. Furthermore, recent clinical trials have shown that targeting higher hemoglobin levels with conventional therapies leads to increased cardiovascular morbidity and mortality, particularly when higher doses of erythropoiesis-stimulating agents are used and in patients who are poorly responsive to therapy. One explanation for the poor response to conventional therapies in some patients is that these treatments do not fully address the underlying cause of the anemia. In many patients with CKD, as with patients with other chronic inflammatory diseases, poor absorption of dietary iron and the inability to use the body's iron stores contribute to the anemia. Recent research suggests that these abnormalities in iron balance may be caused by increased levels of the key iron regulatory hormone hepcidin. This article reviews the pathogenesis of anemia in CKD, the role and regulation of hepcidin in systemic iron homeostasis and the anemia of CKD, and the potential diagnostic and therapeutic implications of these findings.

Initiation of anaemia management in patients with chronic kidney disease not on dialysis in the Veterans Health Administration

Erythropoiesis-stimulating agents (ESAs) are frequently used to treat anaemia of chronic kidney disease (CKD) in the dialysis setting; however, few data are available regarding factors influencing initiation of ESAs and other therapies in non-dialysis patients. A retrospective cohort study of Veterans Health Administration data from 2003 to 2005 for 89 585 patients identified as having CKD and anaemia based on two outpatient estimated glomerular filtration rates <60 ml/min/1.73 m(2) and at least one outpatient haemoglobin (Hb) <11 g/dL. Hb levels, patient demographics, clinical and provider characteristics and procedures predicted ESA treatment initiation over 1 year of follow-up. Multivariable logistic and pooled logistic survival models identified predictors of ESA initiation. Overall, 6381 subjects (7.1%) initiated ESAs within 1 year of the index Hb; initiation was more common (8.6%) for patients with Hb <10 g/dL. Iron therapy use varied by initial Hb levels (27.6% to 52.4%) as did transfusions (12.5% to 42.8%); each was more common at lower Hb levels. Hbs rose to above 11 g/dL for 25-50% of patients in the absence of any treatment or by transfusion/iron therapy. Factors predicting time to ESA initiation included: nephrologist [odds ratio (OR = 2.3)] or haematologist care (OR = 2.2) and iron therapy (OR = 1.6). Transfusions increased for patients with increasing follow-up time. Iron therapy is more common than ESA treatment in patients with CKD and Hbs <11 g/dL in the VA. Correction of anaemia in the absence of any ESA treatment was common at higher Hbs levels, but much less so when Hb levels fell below 10 g/dL.

EVOLUTION OF IV IRON COMPOUNDS OVER THE LAST CENTURY

Administration of intravenous (IV) iron has become pivotal in the management of anaemia in patients with chronic kidney disease (CKD). Since parenteral iron was first introduced for human use in the 1930s, things have come a long way. Seventy years ago, iron was toxic, administered as an iron oxyhydroxide complex. This problem was circumvented with the introduction of compounds containing iron in a core surrounded by a carbohydrate shell. The carbohydrate shell consists of molecules such as dextran, sucrose, dextrin or gluconate. The first dextran-containing IV iron preparations carried a small risk of anaphylaxis, but the more recently introduced low molecular weight iron dextran preparation has significantly less risk of this. Iron reactions occur with all IV iron preparations, but are generally not thought to be immune based. Recently, newer IV iron preparations have appeared in the market, including Ferumoxytol (Feraheme) and ferric carboxymaltose (Ferinject). These latest IV iron preparations do not contain a requirement for a test dose, and a much higher dose of iron can be delivered as a single administration. Thus, giving supplemental iron to man has come a long way since 1930s; we are now in an era when we are able to administer higher doses of iron with acceptable safety and without significant adverse effects. However, the long-term safety of the newer IV iron preparations is not yet established.

Causes and consequences of inflammation on anemia management in hemodialysis patients

Inflammation is common among hemodialysis patients, and evidence is accumulating to suggest that inflammation is a major contributor to morbidity and mortality. Several factors have been suggested as potential causes of inflammation, including infections and the atherosclerosis process, as well as etiologies directly related to kidney disease such as reduced renal function and dialysis. Among several inflammatory biomarkers investigated, serum C-reactive protein (CRP) is the most widely used. In hemodialysis patients, raised CRP levels have been shown to be predictive of cardiovascular events, hospitalization, and all-cause and cardiovascular mortality. Elevated CRP levels may correlate with comorbidities and intercurrent events, all of which may impact the response to erythropoiesis-stimulating agents (ESAs) and lead to higher ESA doses. Most dialysis facilities do not routinely measure CRP, despite recommendations by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. Regular measurement of CRP levels may help providers to understand change in ESA dosing and identify patients at risk for cardiovascular events. This review explores the inter-relationships between inflammation, CRP levels, and anemia management in patients receiving hemodialysis.

A reinforcement learning approach for individualizing erythropoietin dosages in hemodialysis patients

This paper presents a reinforcement learning (RL) approach for anemia management in patients undergoing chronic renal failure. Erythropoietin (EPO) is the treatment of choice for this kind of anemia but it is an expensive drug and with some dangerous side-effects that should be considered especially for patients who do not respond to the treatment. Therefore, an individualized treatment appears to be necessary. RL is a suitable approach to tackle this problem. Moreover, resulting policies are similar to medical protocols, and hence, they can easily be transferred to daily practice. A cohort of 64 patients are included in the study. An implementation of the Q-learning algorithm based on a state-aggregation table and another implementation using the multi-layer perceptron as a function approximator (Q-MLP) are compared with the protocols followed in the Nephrology Unit. The policy obtained by the Q-MLP approach outperforms the hospital policy in terms of the ratio of patients that are within the targeted range of hemoglobin (11.5–12.5g/dl) at the end of the analyzed period, since an increase of 25% is observed. It ensures an improvement in patients’ quality-of-life and considerable economic savings for the health care system due to both the expensiveness of EPO treatment and the costs incurred by the health care system in order to alleviate problems related to EPO over-dosing. It should be pointed out that the approach presented here is completely general, and therefore, it can be applied to any problem of drug dosage optimization.

Target hemoglobin trials in chronic kidney disease: design and interpretation issues

Optimal management of anemia in patients with chronic kidney disease remains a divisive issue within the nephrology community. Because the evidence provided by successive randomized controlled trials has often proven to be incongruent, it is natural to consider whether methodological issues may be responsible. Using four large trials [US Normal Hematocrit, Canadian European Normalization of Hemoglobin, Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) and Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR)], this review article highlights several methodological issues that may be important when trial evidence is translated into clinical practice. Issues discussed include heterogeneity of enrollment criteria, failure to conceal treatment allocation, generalizability of study interventions, systematic use of imbalanced co-interventions [especially dose of erythropoietin stimulating agent (ESA), confusion regarding stopping rules and interim analyses and failure to account for imbalances in important patient characteristics generated at randomization.

Association of Quarterly Average Achieved Hematocrit With Mortality in Dialysis Patients: A Time-Dependent Comorbidity-Adjusted Model

Recent publications suggest that increased mortality is associated with high hematocrit targets in erythropoietin-stimulating agent-treated patients with chronic kidney disease. We aim to further inform the debate about optimal hematocrit targets, advancing the hypothesis that the current hematocrit target may not optimize the survival of patients with end-stage renal disease. Cross-sectional observational study. Medicare dialysis patients from 2002 to 2004 (n = 393,967). Quarterly average hematocrit and erythropoietin alfa (EPO) dose. Mortality hazard ratios from time-dependent Cox proportional hazard models, adjusting for comorbidities. N = 2,712,197 patient-facility quarters. During the study, 100,086 deaths were identified. Percentages of patient quarters within each hematocrit category: hematocrit less than 27% (2.0%), 27% to 28.49% (1.7%), 28.5% to 29.9% (2.9%), 30% to 31.49% (5.2%), 31.5% to 32.99% (9.0%), 33% to 34.49% (14.9%), 34.5% to 35.99% (19.2%), 36% to 37.49% (18.0%), 37.5% to 38.99% (12.0%), 39% to 40.49% (6.4%), 40.5% to 41.99% (3.0%), and 42% or greater (3.1%). Mortality hazard ratios from the fully adjusted model: hematocrit less than 27% (3.11), 27% to 28.49% (2.60), 28.5% to 29.9% (2.14), 30% to 31.49% (1.80), 31.5% to 32.99% (1.44), 33% to 34.49% (1.17), 34.5% to 35.99% (reference), 36% to 37.49% (0.98), 37.5% to 38.99% (1.01), 39% to 40.49% (1.13), 40.5% to 41.99% (1.32), and 42% or greater (1.57). First, potential confounding by indication related to associations between underlying illness and mortality, anemia, and EPO responsiveness. Second, Medicare claims data reflect a range of conditions and degrees of severity not easily translated into the clinical context. Third, for Medicare claims, EPO reporting is not required if EPO is not billed. Greater than 95% of "missing hematocrit" quarters are "EPO = 0" patient quarters. Interpretation of results for the missing hematocrit and EPO = 0 use categories is complicated by data source limitations. We show an association between mortality and low hematocrit in dialysis patients, in part reflecting the presence of comorbidities. We also show an association between increased mortality and high hematocrit. Additional interventional trials should be undertaken to better define the optimal target for anemia management in patients with end-stage renal disease, with careful prospective identification of underlying comorbidities and clinical factors contributing to high erythropoietin-stimulating agent requirement.