Annals for Educators - 21 April 2020
Authors: Darren B. Taichman
Journal: Annals of Internal Medicine (2020)

Web Exclusives21 April 2020Annals for Educators - 21 April 2020FREEDarren B. Taichman, MD, PhDDarren B. Taichman, MD, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/AWED202004210 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical Practice PointsIron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1–Risk Myelodysplastic Syndromes. A Randomized TrialIron overload in transfusion-dependent patients with myelodysplastic syndrome (MDS) can lead to poorer clinical outcomes. The effectiveness of iron chelation therapy in patients with lower-risk MDS is limited. This phase 2 clinical trial explores whether iron chelation is associated with clinical benefit in this group compared with placebo.Use this study to:Start a teaching session with a multiple-choice question. We've provided one below!Ask your learners how MDS presents. How is the diagnosis made? Use the information in DynaMed: Myelodysplastic Syndrome, a benefit of your ACP membership. How is MDS managed?Why does iron overload occur with frequent transfusions? What are the potential complications of iron overload? Use the information in DynaMed: Transfusional Iron Overload. What did this study find? How should the results be interpreted in light of the slower than anticipated study recruitment? Do your learners think that iron chelation therapy (deferasirox) should be used in patients with MDS?Effects of Interleukin-1β Inhibition on Incident Anemia. Exploratory Analyses From a Randomized TrialThese analyses of data from a randomized controlled trial explored whether interleukin-1β inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among patients with prevalent anemia.Use this study to:Ask your learners how inflammation is thought to contribute to “anemia of chronic disease.” The authors discuss potential mechanisms in the paper's introduction and discussion.How is anemia in this setting diagnosed? What other potential causes of anemia should be considered?What did the study find? What findings support the conclusion that moderation of inflammation was beneficial for anemia in the study participants? See the next paper (Understanding Clinical Research) for a tutorial.Understanding Clinical ResearchFinding the Pathway: Mediation Analyses in Randomized Controlled TrialsThis article summarizes the goals, assumptions, and challenges of mediation analysis, a rapidly developing statistical methodology in medical and public health research. It uses the study above of interleukin-1β inhibition and anemia to illustrate mediation analysis.Use this feature to:Ask your learners what is meant by “mediation analysis.” What does it aim to assess?The authors emphasize that mediation analysis can help to decompose the natural direct and indirect effects (see Figure 1). Do your learners understand the difference?What would the natural direct effect be in the trial discussed above? What would the natural indirect effect be?For Program DirectorsMisinterpretation of the American Board of Internal Medicine Leave Policies for Resident Physicians Around Parental LeaveThis study presents the results of a survey of program directors (PDs) at U.S. internal medicine training programs to assess knowledge of American Board of Internal Medicine (ABIM) resident leave policies. Although about half of PDs reported understanding the ABIM leave policies, the vast majority did not correctly interpret them. The policies are outlined and explained.Humanism and ProfessionalismOn Being a Doctor: The Patient in Front of YouDr. Sanders realized that his patient's pain and his process were clearly incompatible.Use this essay to:Listen to an audio recording, read by Dr. Michael LaCombe. Ask your learners whether they have discovered that their intended agenda with a patient was not what was most needed at the moment.How did they respond?On Being a Doctor: The Italian BelleDr. Tucker recalls that her patient had captured her heart, but now it was time to talk about her patient's heart.Use this essay to:Listen to an audio recording, read by Dr. Virginia Hood. Ask your learners what life-altering lessons their patients have taught them.MKSAP 18 QuestionA 76-year-old woman is evaluated for worsening fatigue. She reports no additional symptoms. Medical history is significant for myelodysplastic syndrome diagnosed 3 years ago, which has required the transfusion of 1 to 2 units of blood every 5 to 6 weeks to maintain a hemoglobin level of approximately 8 g/dL (80 g/L); she has exertional dyspnea when the hemoglobin level drops below 7 g/dL (70 g/L).On physical examination, vital signs are normal. The abdomen is soft. Conjunctival pallor is noted. The examination is otherwise noncontributory.Laboratory studies show a hemoglobin level of 7.5 g/dL (75 g/L) and a serum ferritin level of 1638 ng/mL (1638 μg/L).Which of the following is the most appropriate management?A. Begin deferasiroxB. Begin succimerC. Perform therapeutic phlebotomyD. Withhold transfusion until hemoglobin level is 6 g/dL (60 g/L)Correct AnswerA. Begin deferasiroxEducational ObjectiveTreat secondary iron overload.CritiqueThis patient should begin deferasirox for treatment of secondary iron overload. In most cases, secondary iron overload occurs in patients with severe anemia who require chronic transfusion therapy. Because iron excretion has no regulated mechanism, multiple transfusions (for anemias not stemming from blood loss or iron deficiency) lead to iron overload, with subsequent secondary organ damage. If these anemias resolve (either from hematopoietic stem cell transplantation or remission of leukemias), phlebotomy should be initiated. When anemia is ongoing, such as in this patient, iron chelation is required, for which deferoxamine or deferasirox may be used. These agents are relatively toxic, leading to potential kidney and liver damage, agranulocytosis, or ocular and ophthalmic disorders; therefore, careful monitoring is required. Serum ferritin level correlates with iron burden in patients receiving chronic transfusion, and levels greater than 1000 ng/mL (1000 μg/L) are generally considered an indication for therapy. Deferoxamine is only available for parenteral administration, which is much less convenient in the long-term outpatient setting than oral iron chelation. The availability of oral iron chelation with deferasirox has increased medication adherence for patients who develop secondary iron overload from chronic transfusions for hemoglobinopathies or myelodysplastic syndrome. Deferasirox commonly causes gastrointestinal side effects. The medication is often better tolerated in the evening, before the evening meal.Succimer is used to chelate lead and enhance excretion in patients with chronic lead intoxication. It would not be used to treat iron overload.Therapeutic phlebotomy is the management of choice for hereditary (primary) hemochromatosis. It effectively removes 200 mg of iron with each pint of blood removed. However, therapeutic phlebotomy is not suitable for patients with symptomatic anemia who require chronic transfusion, as is the case with this patient.Withholding transfusion is not appropriate because of this patient's age and her symptomatic anemia.Key PointSecondary iron overload from chronic transfusions can be effectively treated with oral chelation agents, such as deferasirox.BibliographyNolte F, Angelucci E, Breccia M, Gattermann N, Santini V, Vey N, et al. Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with deferasirox in transfusion dependent patients with myelodysplastic syndrome - emphasis on optimized dosing schedules and new formulations. Leuk Res. 2015;39:1028-33.Do you like reading Annals for Educators? Receive it direct to your inbox. Sign up for the Annals for Educators alert today. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Associate Dean of Graduate Medical Education and Affiliations, Thomas Jefferson University. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 April 2020Volume 172, Issue 8Page: ED8KeywordsAnemiaClinical trialsExcretionGraduate medical educationHeartHemoglobinInflammationMyelodysplastic syndromesPhlebotomySerum ferritin levels ePublished: 21 April 2020 Issue Published: 21 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...