Variation in health plan coverage of ESAs for anemia due to chronic kidney disease.

BACKGROUND: Because health plans each issue their own policies, drug coverage can vary. This variation can result in patients having unequal access to treatment. In this study, we evaluate commercial health plans' coverage policies for erythropoiesis-stimulating agents (ESAs) for patients with anemia resulting from chronic kidney disease (CKD). OBJECTIVES: To assess how a set of US commercial health plans cover ESAs for patients with anemia due to CKD. Our second objective was to examine the evidence that the plans reviewed when formulating their coverage policies. METHODS: We used the Tufts Medical Center Specialty Drug and Evidence and Coverage Database to identify coverage policies issued by 17 of the largest US commercial health plans for ESAs. The following drugs were indicated for anemia due to CKD: darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, epoetin alfa (available as two brands), and epoetin alfa-epbx. Coverage policies were current as of May 2019. We determined whether the health plans applied any restrictions, such as step therapy protocols or patient subgroup restrictions, in their coverage policies. We categorized the evidence that plans cited to support their policies into seven categories: randomized controlled trials (RCTs), real-world evidence (RWE) studies (studies based on data collected in a real-world setting), other clinical studies (eg, single arm trials), systematic reviews and/or meta-analyses, clinical or treatment guidelines, health technology assessments, and economic evaluations. RESULTS: We categorized 72.5% of coverage policies (58/80 policies) as equivalent to the FDA label and 27.5% (22/80 policies) as more restrictive. In restricted policies, plans most often applied step therapy protocols (18/22 policies), followed by prescriber requirements (4/22 policies), and patient subgroup restrictions (3/22 policies). Five health plans applied restrictions in at least half of their coverage policies; seven plans did not apply restrictions in any policy. Plans that cited evidence reviewed an average of 10 citations across their ESA coverage policies, ranging from one to 29 studies. Plans varied with respect to the types of cited studies: at least 50% of evidence cited by five health plans was RCTs, while half or more of the evidence cited by four health plans was clinical or treatment guidelines. CONCLUSIONS: Health plans varied in how they covered ESAs for patients with anemia due to CKD and in the evidence cited in their coverage policies. Inconsistencies in plans' coverage policies may have implications for patients' access to ESAs. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development and Commercialization. Sanon, Redmond, and Mogahadam are employed by Otsuka Pharmaceutical. Michalopoulos was employed by Otsuka Pharmaceutical at the time of this study. Margaretos, Panzer, and Chambers are employed by Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health. Lai was with Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health at the time of this study.

Conversion from Aranesp® to NESP® in dialysis patients-Exploration of dosing strategies and the feasibility of extending the dosing interval.

AIM: Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. METHODS: Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. RESULTS: Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. CONCLUSION: Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.

Effects of a multifaceted intervention to promote the use of intravenous iron sucrose complex instead of ferric carboxymaltose in patients admitted for more than 24 h.

PURPOSE: Although more practical for use, the impact of ferric carboxymaltose (FCM) on the hospital budget is considerable, and intravenous iron sucrose complex (ISC) represents a cost-saving alternative for the management of iron deficiency anemia in patients during hospitalization. The Drug Committee decided to reserve FCM for day hospitalizations and contraindications to ISC, especially allergy. ISC was available for prescription for all other situations. METHODS: The impact of a multifaceted intervention promoting a switch from FCM to ISC was evaluated using an interrupted time series model with segmented regression analysis. The standardized rate of the dispensing of FCM, ISC, and oral iron by the hospital pharmacy, as well as the rate of the dispensing of packed red blood cells and the number of biological iron status measurements, was analyzed before and after the intervention. RESULTS: There was an immediate decrease in FCM consumption following the intervention, with a reduction of 88% (RR: 0.12 [CI95% 0.10 to 0.15]). Conversely, there was a large increase in ISC use (RR: 5.1 [CI95% 4.4 to 5.9]). We did not observe a prescription shift to packed red blood cells or oral iron after the intervention. The time series analysis showed the frequency of iron status testing to remain stable before and after. The direct savings for intravenous iron for 8 months were 187,417.54 €. CONCLUSION: Our intervention to lower the impact of intravenous iron therapy on the hospital budget was effective.

Oral high-dose sucrosomial iron vs intravenous iron in sideropenic anemia patients intolerant/refractory to iron sulfate: a multicentric randomized study.

Iron deficiency anemia is among the most frequent causes of disability. Intravenous iron is the quickest way to correct iron deficiency, bypassing the bottleneck of iron intestinal absorption, the only true mechanism of iron balance regulation in human body. Intravenous iron administration is suggested in patients who are refractory/intolerant to oral iron sulfate. However, the intravenous way of iron administration requires several precautions; as the in-hospital administration requires a resuscitation service, as imposed in Europe by the European Medicine Agency, it is very expensive and negatively affects patient's perceived quality of life. A new oral iron formulation, Sucrosomial iron, bypassing the normal way of absorption, seems to be cost-effective in correcting iron deficiency anemia at doses higher than those usually effective with other oral iron formulations. In this multicentric randomized study, we analyze the cost-effectiveness of intravenous sodium ferrigluconate vs oral Sucrosomial iron in patients with iron deficiency anemia refractory/intolerant to oral iron sulfate without other interfering factors on iron absorption.

The use of intravenous iron in pregnancy: for whom and when? A survey of Australian and New Zealand obstetricians.

BACKGROUND: Iron deficiency anaemia in pregnancy (IDAP) affects 11-18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP. METHODS: An online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing. RESULTS: Of 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed. CONCLUSIONS: Almost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.

Intravenous ferric carboxymaltose for iron deficiency anemia in dialysis patients: Effect of a new protocol adopted for a hemodialysis limited assistance center.

Iron and erythropoietin deficiencies are determinants of anemia in chronic kidney disease. In hemodialysis (HD) patients, intravenous (IV) iron is associated with a greater hemoglobin (Hb) production and better erythropoietin response but may be associated to hypersensitivity reaction. After the 2013 European Medicines Agency report regarding early detection/management of iron allergic reactions, IV iron administration dramatically reduced in Italian Hemodialysis-Limited-Assistance-Centre (HD-CAL) where a physician is present only once a week. Objective of the study was providing an effective and secure IV iron administration protocol for HD-CAL patients. IV ferric carboxymaltose (FCM) administration was more effective and better tolerated than sodium ferric gluconate for iron deficiency correction and resolution of anemia in 24 patients undergoing HD in our HD-CAL. Six months of FCM IV treatment once a week increased ferritin and Hb compared to sodium ferric gluconate once a week leading to decreased erythropoietin consumption from 24 000 to 15 000 U/patient/week with an erythropoietin annual expense reduction. No blood transfusions, gastrointestinal intolerance or other adverse effects were reported. The FCM IV administration protocol for our HD-CAL patients was safe and no adverse events were reported, resulting in significantly increased ferritin, transferrin saturation, and Hb levels, reduction of erythropoietin requirements, and consequently reduction of erythropoietin expenses.

A patient-level cost-effectiveness analysis of iron isomaltoside versus ferric carboxymaltose for the treatment of iron deficiency anemia in the United Kingdom.

Objectives: Intravenous iron is the recommended treatment for patients with iron deficiency anemia (IDA) where oral iron is ineffective or rapid iron replenishment is required. Two high-dose, rapid-administration intravenous iron formulations are currently available in the UK: iron isomaltoside 1000/ferric derisomaltose (IIM) and ferric carboxymaltose (FCM). An indirect treatment comparison (ITC) recently showed that improvement from baseline hemoglobin was significantly larger with IIM than FCM. The objective was to use the ITC findings to evaluate the cost-effectiveness of IIM versus FCM from the UK healthcare payer perspective.Methods: A patient-level simulation model was developed in R to evaluate the cost per patient experiencing hematological response with IIM versus FCM. The model generated a simulated cohort from parametric distributions of baseline hemoglobin and bodyweight. Changes in hemoglobin were modeled based on data from the ITC, covaried with baseline hemoglobin based on patient-level data from a randomized controlled trial. Posological models of the iron formulations were developed based on the summaries of product characteristics. UK-specific costs were based on healthcare resource groups.Results: The proportion of patients experiencing hematological response was 9.0% higher with IIM relative to FCM (79.0% versus 70.0%), based on modeling of clinically realistic, correlated distributions of baseline hemoglobin and change from baseline hemoglobin. The mean number of infusions needed to administer the required dose was 1.92 with FCM, versus 1.38 with IIM, resulting in costs of £637 and £457 per treated patient with FCM and IIM respectively, corresponding to respective costs of £910 and £579 per responder.Conclusions: The analysis showed that using IIM rather than FCM in patients with IDA was dominant and would reduce the number of iron infusions required to correct iron deficiency, thereby reducing the costs associated with IDA treatment and simultaneously increasing the proportion of patients with IDA experiencing a clinically meaningful hematological response.

Oral Sucrosomial® iron versus intravenous iron for recovering iron deficiency anaemia in ND-CKD patients: a cost- minimization analysis.

BACKGROUND: Oral iron is recommended as first line treatment of anemia in non-dialysis chronic kidney disease (ND-CKD) patients. Sucrosomial® iron, a new generation oral iron with high absorption and bioavailability and a low incidence of side effects, has shown to be not inferior to intravenous (IV) iron in the replacement of iron deficiency anemia in patients with ND-CKD. Besides the clinical benefit, it is also important to determine the comparative total costs of oral versus IV iron administrations. The aim of this study was to perform a cost-minimization analysis of oral Sucrosomial iron, compared with IV iron gluconate from an Italian societal perspective. METHODS: Cost analysis was performed on the 99 patients with ND-CKD and iron-deficiency anemia of the randomized trial by Pisani et al. Human and material resources utilization was recorded during each iron administration. According to study perspective, direct and indirect costs were considered. Costs for each resource unit were taken from official Italian sources. Probabilistic sensitivity analyses were carried out to test the robustness of the results. RESULTS: The base case analysis showed an average cost/cycle per patient of € 111 for oral iron and € 1302 for IV iron. Thus, the potential saving was equal to € 1191 per patient/cycle. The sensitivity analysis showed that the most sensitive driver is the time loss by patient and caregivers for the therapy and related-care, followed by the minutes of nursing care and the number of kilometres travelled to reach the referral centre. DISCUSSION: This study showed that oral Sucrosomial® iron could offer specific advantages in terms of potential savings, and allowed identifying some implications for future research. Such advantages still persist with the new single dose IV iron formulation available in the market, although to a lesser extent.

Cost-minimization analysis between intravenous iron sucrose and iron sucrose similar in hemodialysis patients.

OBJECTIVES: Intravenous iron and erythropoiesis-stimulating agents are used to manage anemia in chronic hemodialysis patients. The interchangeability between intravenous iron sucrose preparations is still debated. We evaluated how cost and effectiveness were impacted when chronic hemodialysis patients were switched from an original iron sucrose product to an iron sucrose similar preparation. METHODS: A single center sequential observational retrospective study was conducted at a French hospital. The same patients were followed during two 24-week periods (iron sucrose in period P1; and iron sucrose similar in period P2). Anemia-related treatment costs were assessed in P1 and P2 from a hospital perspective. Sensitivity analyses were performed to assess the robustness of the results. RESULTS: Our study included 109 patients (105 analyzed patients and 4 patients with missing data). The mean hemoglobin level was not different between P1 and P2 (p = 0.92). The mean differential cost per patient was + €13.90 (P2 - P1). The factors with the biggest impact on this result were the prices of epoetin alfa and iron sucrose. CONCLUSION: This cost minimization analysis suggests that for chronic hemodialysis patients, iron sucrose and iron sucrose similar have the same efficacy and that using iron sucrose similar was more expensive in 66.7% of iterations.

An assessment for diagnostic and therapeutic modalities for management of pediatric Iron defficiency Anemia in Saudi Arabia: a crossectional study.

INTRODUCTION: Iron deficiency anemia (IDA) is a global public health issue that affect more than 2 billion individuals worldwide. However evidence for optimal management of IDA is lacking. METHODS: To assess the diagnostic criteria and therapeutic modalities for pediatric IDA employed by physicians in a major public healthcare facility in Riyadh, a validated questionnaire including demographic data and patient case-scenarios related to diagnosis and treatment of IDA was employed. Robust regression analysis was used to identify factors associated with overall score of participants. RESULTS: Of the 166 physicians surveyed 147(88.6%) were included in the study. Wide variability was observed in IDA diagnosis and therapy practises. For nutritional IDA, only 15.6% recommended no other laboratory tests in addition to CBC. The majority preferred treatment with ferrous sulfate (77.6%) divided into two doses (57.1%), but the total daily elemental iron doses varied widely from 2 to 6 mg/kg. For intravenous iron, 42.9% recommended iron dextran, 32.7% iron sucrose, and 13.4% would continue oral iron. Of all assessed factors, median score was significantly highest in pediatric hematologists compared with pediatricians, family medicine specialists and GPs; p = 0.007, and those work in tertiary care compared with those in primary care; p = 0.043. However, in multivariate robust regression analysis, overall score was only significantly associated with professional qualification [pediatric hematologist ß = 13.71,95%CI 2.48-24.95, p = 0.017; pediatrician ß = 1.77,95%C (- 6.05-9.59, p = 0.66; family medicine ß = 2.66,95%CI-4.30-9.58, p = 0.45 compared with general practitioner]. CONCLUSION: Wide variations exist among physicians in diagnosis and treatment of pediatric IDA. Intervention programs and national guidelines are urgently needed.

Time spent on erythropoietin stimulating agents administration in hemodialysis centers in Panama: a time and motion study.

Objectives: There is a lack of data in Panama on the potential differences in total healthcare professional (HCP) time between routine administrations of short-acting erythropoietin simulating agents (ESAs) (i.e. epoetin alfa) and continuous erythropoietin receptor activator (CERA) (i.e. methoxy polyethylene glycol-epoetin beta). This study aimed to quantify the HCP time associated with a single administration of epoetin alfa and CERA for the treatment of anemic patients with chronic kidney disease (CKD) on hemodialysis. Methods: This was a multi-center, cross-sectional study, using a time-and-motion methodology. Costs related to HCP time and consumables usage associated with administration of epoetin alfa and CERA were estimated. Results: Based on 60 administrations of either CERA or epoetin alfa, the estimated savings in mean total active HCP time were 2.34 (95% confidence interval = 1.87-2.81) min (-30%) per administration. When extrapolating to a full year's treatment with intravenous ESA, it would require a total of 20.3 (95% CI = 19.90-20.71) h of HCP time for epoetin alfa vs 1.1 (95% CI = 1.01-1.19) h for CERA per patient per year. Estimated savings in active HCP time per patient per year were 19.20 (95% CI = 19.20-19.21) h (-95%). This, in turn, translates into staff cost efficiency that favors Mircera with an estimated annual saving of $78.24 (95% CI = 78.24-78.28) (-95%) per patient. Conclusions: Data from a real-world setting showed that the adoption of CERA could potentially lead to a reduction in active HCP time. Highlights Few comparative data have explored the costs and potential savings of using long-acting erythropoietin-stimulating agents (ESA) instead of short-acting ESAs to treat anemia in CKD patients on hemodialysis. This time-and-motion study shows that use of CERA reduces total healthcare professional time and could represent a save for an institution in a real-world setting in Panama.

A Retrospective Comparative Study of Different Methods of Blood Management in Total Knee Replacement.

Perioperative blood management is essential to minimize allogeneic blood transfusion in total knee replacement. The effect of preoperative administration of erythropoietin, intraoperative cell saver, tranexamic acid, and restrictive transfusion strategies on allogeneic transfusion is studied in total knee replacement. A retrospective comparative study of 106 patients who underwent total knee replacement in different time periods was performed. Group A (n 1 = 45) underwent restrictive strategies of transfusion between 2009 and 2010. Group B (n 2 = 24) includes patients where erythropoietin of either 10.000 IU or 20.000 IU was given preoperatively. Patients of Group C (n 3 = 21) underwent autologous washed erythrocytes transfusion through a cell saver. Lastly, in Group D (n 4 = 15) tranexamic acid dose of 1 gr IV was given intraoperatively. The preoperative and discharge hemoglobin together with total units of blood transfusion and creatinine levels was studied. Tranexamic acid noted the least units of blood transfusion (mean = 0.82 units/patient, p < 0.001, CI 95%) in contrast to the two regimens of erythropoietin (1.16 units/patient) OrthoPAT (1.43 units/patient) and restrictive strategies (1.92 units/patient). The mean preoperative hemoglobin was 13.37 g/dL with no statistical difference among the groups of patients. The postoperative mean hemoglobin was 10.59 with no statistical difference among the groups of patients too. Additionally, the mean creatinine level was 0.93 mg/dL; however, no statistical difference among the groups of patients was noted. Finally, tranexamic acid seemed to be the most cost-effective regime. In our study, tranexamic acid proved its superiority concerning the postoperative blood transfusion on patients undergoing total knee replacement, in comparison with the other existing methods of perioperative blood management. This is a Level III, retrospective comparative study.

Treating Anemia in the Preanesthesia Assessment Clinic: Results of a Retrospective Evaluation.

BACKGROUND: Perioperative anemia is challenging during hospital stay because anemia and red blood cell (RBC) transfusions are associated with an increased morbidity and mortality. With the implementation of patient blood management (PBM), a preanesthesia assessment clinic to screen and treat anemia before elective surgery was institutionalized at Muenster University Hospital, Germany. The main objective of this study was to evaluate the association between treating preoperative anemic patients with intravenous iron (IVI) and (primarily) presurgical hemoglobin levels and (secondarily) use of RBCs and mortality. METHODS: Between April 1, 2014, and July 4, 2016, patients scheduled for elective surgery with a risk for RBC transfusions >10% in 2013 were screened for preoperative anemia and, if indicated, treated with IVI. Patients' data, time span between visit in the anesthesia/PBM clinic and surgery, demographic data, type of surgery, the difference of hemoglobin levels between visit and surgery, RBC transfusion, infectious-related International Classification of Disease codes during hospital stay, and 1-year survival were determined retrospectively by screening electronic data files. In addition, patients were interviewed about adverse events, health-related events, and infections via telephone 30, 90, and 365 days after visiting the anesthesia/PBM clinic. RESULTS: A total of 1101 patients were seen in the anesthesia/PBM clinic between days -28 and -1 (median [Q1-Q3], -3 days [-1, -9 days]) before elective surgery. Approximately 29% of patients presented with anemia, 46.8% of these anemic patients were treated with ferric carboxymaltose (500-1000 mg).In the primary analysis, hemoglobin levels at median were associated with a reduction between the visit in the anesthesia/PBM clinic and the surgery in all nonanemic patients on beginning of medical treatment (nonanemic patients at median -2.8 g/dL [-4, -0.9 g/dL], while anemic patients without IVI presented with median differences of -0.8 g/dL [-2, 0 g/dL] and anemic patients with IVI of 0 g/dL [-1.0, 0.5 g/dL]). Hemoglobin levels raised best at substitution 22-28 days before surgery (0.95 g/dL [-0.35, 1.18 g/dL]). Due to the selection criteria, transfusion rates were high in the cohort. Overall, there was no association between IVI treatment and the use of RBC transfusions (odds ratio for use of RBCs in anemic patients, no IVI versus IVI: 1.14; 95% confidence interval, 0.72-1.82). Patients treated with or without IVI presented a comparable range of International Classification of Disease codes related to infections. Telephone interviews indicated similar adverse events, health-related events, and infections. Cox regression analysis showed an association between anemia and reduced survival, regardless of IVI. CONCLUSIONS: An anemia clinic within the preanesthesia assessment clinic is a feasible and effective approach to treat preoperative anemia. The IVI supplementation was safe but was associated with decreased RBC transfusions in gynecology/obstetric patients only. The conclusions from this retrospective analysis have to be tested in prospective, controlled trials.

Financial impact of intravenous iron treatments on the management of anaemia inpatients: a 1 year observational study.

Background Intravenous (IV) iron preparations bypass the difficulties (malabsorption and side effects) associated with oral iron for the treatment of iron deficiency anaemia (IDA). Ferric carboxymaltose (FCM) can be administered as a single infusion over short periods of time but is more expensive than iron sucrose (IS) when the patients are hospitalized. Objectives To evaluate the appropriateness of FCM prescriptions and to establish the economic impact of this management (including disease coding) compared to the use of IV IS. Setting This study was conducted for inpatients in all departments (orthopaedic department, gastroenterology department and two units of the internal medicine department) where FCM was widely prescribed. Method We retrospectively identified 224 patients, diagnosed with IDA using laboratory parameters and/or disease coding, who received FCM between January and December 2014. Main outcome measure The primary outcome was the rate of appropriateness of FCM prescriptions and the financial impact compared to IV IS. Results 89 Patients were included. The total additional cost for an inappropriate prescription of IV FCM (68% of cases) was of 6053 €. The total incremental cost of unsuitable disease coding was estimated at 31,688 €. Indications for IV FCM were categorized: intestinal bleeding (31%), malabsorption (17%), intolerance (9%) and refractory to oral iron (7%). The majority of patients (62%) received 1000 mg of FCM per week. The average length of hospital stay was of 10 days. Conclusion The prescription of IV iron was appropriate in most cases but did not necessarily require FCM. The use of IV IS, in many cases, could present a cost-saving option for inpatients with IDA. The lack of an IDA coding generated incremental costs.

The Use of Magnetic Resonance Imaging for Non-Invasive Assessment of Venofer® Biodistribution in Rats.

PURPOSE: The aim of this study was to determine the potential of magnetic resonance imaging to evaluate the biodistribution of exogenous iron within 24 h after one single injection of Venofer® (iron sucrose). METHODS: Venofer® was evaluated in vitro for its ability to generate contrast in MR images. Subsequently, iron disposition was assessed in rats with MRI, in vivo up to 3 h and post mortem at 24 h after injection of Venofer®, at doses of 10- and 40 mg/kg body weight (n = 2 × 4), or saline (n = 4). RESULTS: Within 10-20 min after injection of Venofer®, transverse relaxation rates (R2) clearly increased, representative of a local increase in iron concentration, in liver, spleen and kidney, including the kidney medulla and cortex. In liver and spleen R2 values remained elevated up to 3 h post injection, while the initial R2 increase in the kidney was followed by gradual decrease towards baseline levels. Bone marrow and muscle tissue did not show significant increases in R2 values. Whole-body post mortem MRI showed most prominent iron accumulation in the liver and spleen at 24 h post injection, which corroborated the in vivo results. CONCLUSIONS: MR imaging is a powerful imaging modality for non-invasive assessment of iron distribution in organs. It is recommended to use this whole-body imaging approach complementary to other techniques that allow quantification of iron disposition at a (sub)cellular level.

Intravenous iron treatments for iron deficiency anemia in inflammatory bowel disease: a budget impact analysis of iron isomaltoside 1000 (Monofer) in the UK.

INTRODUCTION: Iron deficiency is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment for clinically active IBD or previous oral iron intolerance. The aim of the present study was to develop a comparative model of iron deficiency and delivery for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency anemia associated with IBD. Areas covered: A model was developed to evaluate iron delivery characteristics, resource use and costs associated with IIM, FCM, LMWID and IS. Iron deficiency was modeled using dosing tables and retreatments were modeled based on a pooled retrospective analysis. The analyses were conducted over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin levels of 10.77 g/dL based on observational data. Expert opinion: The modeling analysis showed that using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS, respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

Administration of erythropoiesis-stimulating agents in patients undergoing haemodialysis: A time and motion study.

BACKGROUND: International guidelines recommend treatment of anaemia due to chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs). OBJECTIVE: To document the time required and the cost in terms of nursing time to prepare and administer ESAs to patients on facility based haemodialysis (HD) with anaemia due to CKD before and after the introduction of long-acting ESAs. DESIGN: A time and motion study was implemented at four HD units in Australia to determine the time and costs associated with preparing and administering ESAs before and after the introduction of long-acting ESAs. PARTICIPANTS: This was a prospective, observational study of workplace practices at four HD units in Australia. MEASUREMENTS: Outcome data included the time taken to prepare, and administer ESAs. RESULTS: The time costs of preparation and administration per patient per year had a wide variability within each unit and ranged from Australian AUD$55.75 (38 euros) to AUD$90.49 (62 euros) before the introduction of long-acting ESAs. This dropped by 73-80% following the introduction of long-acting ESAs, representing an annual cost savings of between AUD$2,591 and AUD$5,914 if all patients on HD were switched to a long acting ESA. CONCLUSION: Switching from a short-acting to a long-acting ESA in HD units leads to a significant reduction in time costs of health professionals in preparation and administration of ESAs by up to 80%. Practical application: This time and motion study has added further evidence on reduction of human effort by taking advantages of new research development, such as the long acting ESAs.

Is There a Role for Preoperative Iron Supplementation in Patients Preparing for a Total Hip or Total Knee Arthroplasty?

BACKGROUND: Several treatment modalities exist for the treatment of perioperative anemia. We determined the effect of oral iron supplementation on preoperative anemia, and the use of blood-conserving interventions before total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 3435 total joint arthroplasties (1461 THAs and 1974 TKAs) were analyzed during 2 phases of a blood conservation program. The first phase used erythropoietin alfa (EPO) or intravenous (IV) iron for patients at risk for perioperative anemia. The second phase included these interventions, as well as preoperative iron supplementation. The effect on preoperative hemoglobin (Hb) and serum ferritin, as well as EPO and IV iron utilization, was determined. RESULTS: Oral iron therapy increased preoperative Hb level by 6 g/L (P < .001) and 7 g/L (P < .001) in the hip and knee cohorts, respectively. Serum ferritin level rose by 80 µg/L (P < .001) and 52 µg/L (P < .001) in the hip and knee cohorts, respectively. The number of patients with an Hb level <130 g/L was significantly reduced (P < .001 for both cohorts), as were patients with serum ferritin levels <35 µg/L (P = .002 for hip and P < .001 for knee cohorts). Utilization of EPO reduced from 16% to 6% (P < .001) and 18% to 6% (P < .001) in the hip and knee cohorts, respectively. Utilization of IV iron reduced from 4% to 2% (P = .05) and 5% to 2% (P < .001) in the hip and knee cohorts, respectively. CONCLUSION: Oral iron therapy reduced the burden of perioperative anemia and reduced utilization of other blood-conserving therapies before THA and TKA. Future research should delineate the cost-effectiveness of oral iron therapy.

An infant and mother with severe B12 deficiency: vitamin B12 status assessment should be determined in pregnant women with anaemia.

The vitamin B12 status of infants depends on maternal B12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B12 injections. Marked catch-up of developmental milestones was noted after treatment with B12. Investigations of parents showed normal B12 in the father and combined B12 and iron deficiency in the mother. Maternal B12 deficiency, most likely masked by iron deficiency, led to severe B12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B12 status during pregnancy.

Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome.

Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction ( P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.