Annals for Educators - 16 January 2018
Authors: Darren B. Taichman
Journal: Annals of Internal Medicine (2018)

Web Exclusives16 January 2018Annals for Educators - 16 January 2018FREEDarren B. Taichman, MD, PhDDarren B. Taichman, MD, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/AFED201801160 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical Practice PointsUse of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease. A Systematic ReviewThis systematic review describes adverse events in patients with cancer and concomitant autoimmune disease who received cancer immunotherapy with checkpoint inhibitors (CPIs).Use this review to:Start a teaching session with a multiple-choice question. We've provided one below!Ask your learners what CPIs are. How do they work as antitumor agents? For what types of cancer have they been shown to be successful? Invite an oncologist to join your discussion.Why have patients with autoimmune disease been excluded from clinical trials of CPIs? Why might the mechanism of action of CPIs lead to autoimmune adverse events?Review the results of this study. What are the limitations of the available data? Use the authors' discussion and the accompanying editorial to help answer this question. How are the observational reports identified in this review helpful for clinical practice and further research, despite their weaknesses?Comparison of Five Major Guidelines for Statin Use in Primary Prevention in a Contemporary General PopulationFive professional organizations in Europe and North America have published guidelines for using statins to prevent atherosclerotic cardiovascular disease. Application of the different guidelines to a single population aged 40 to 75 years would result in as few as 15% or as many as 44% of participants receiving statins. This study estimated how many cardiovascular events would be prevented using each guideline.Use this paper to:Ask your learners how they decide which patients should use statins for primary prevention of cardiovascular disease.What do the guidelines recommend? Which ones do your learners know about?Review Table 1, which summarizes the approaches taken by each of the 5 major guidelines. What are the key differences?Ask your learners why following each of the guidelines results in a different number of patients recommended for statin use in the population modeled here and why the number of cardiovascular events differs.Why do guideline groups issue different recommendations despite using largely the same evidence? Use the accompanying editorial to help frame your discussion. What approach do your learners intend to follow? Why? What are the risks and benefits of their planned approaches?Comparative Effectiveness of Implementation Strategies for Blood Pressure Control in Hypertensive Patients. A Systematic Review and Meta-analysisThis meta-analysis of data from 100 trials examines the comparative effectiveness of 8 implementation strategies for blood pressure control in adults with hypertension.Use this review to:Ask your learners what strategies are used in their practices to help patients reach blood pressure treatment goals.Review the list of implementation strategies in Table 1. Which ones are used at your center? Before reviewing this study's results, ask your learners how well they think each of the listed strategies performs.Review the results. Are your learners surprised?Why do your learners think certain strategies work better than others?If team-based approaches to blood pressure control are used at your institution's outpatient practices, who is involved? Who monitors performance in your practice? How is performance assessed? Invite a quality improvement officer to join your discussion.Why do your learners think that involvement of nonphysician team members was found to be useful? What are the potential benefits, as well as barriers to their involvement? Use the accompanying editorial to help frame your discussion. Log on and answer the accompanying questions to earn CME/MOC credit for yourself!Diagnosis of Venous Thromboembolism: 20 Years of ProgressThis special article details state-of-the-art algorithms for diagnosing deep venous thrombosis (DVT) and pulmonary embolism (PE) in adults, including pregnant women.Use this paper to:Ask your learners why establishing a pretest clinical probability of either DVT or PE is important. How does the pretest probability affect the choice of test and the interpretation of results?How do your learners assess pretest probability? Do they do so in a systematic manner?What is the PERC tool, and when is it useful?Review the algorithms for evaluation of potential DVT and PE. Are these the approaches followed by your learners? Why or why not?What imaging tests should be used for suspected DVT or PE in a pregnant patient? Does a V/Q or CT angiographic study expose the patient or fetus to more radiation?Getting Credit for What You DoBy simply logging on when you click through to see the papers highlighted in this alert, you'll be eligible to claim point-of-care CME and MOC points. Logging on at the top right of the Web site takes seconds. Papers you look at when logged in will be recorded, allowing you to claim CME/MOC credit later by answering 2 simple questions about how you used the content. Give yourself the credit you deserve!MKSAP 17 QuestionA 55-year-old woman is evaluated in the emergency department for a 3-day history of diarrhea. She reports seven to eight stools daily without vomiting. She also notes abdominal cramping without vomiting and has been able to maintain adequate fluid intake. Medical history is significant for metastatic malignant melanoma, for which she recently completed the third of four planned doses of ipilimumab therapy. She has no history of inflammatory bowel disease, recent antibiotic use, recent travel, or consumption of uncooked foods. The remainder of the medical history is noncontributory, and she takes no other medications.On physical examination, temperature is 37.5 °C (99.5 °F), blood pressure is 125/85 mm Hg, pulse rate is 90/min without orthostatic changes, and respiration rate is 14/min. The abdomen is soft and nontender with increased bowel sounds. The remainder of the physical examination is normal.Laboratory studies:Hemoglobin12.2 g/dL (122 g/L)Leukocyte count9300/μL (9.3 × 109/L) with normal differentialAlanine aminotransferase120 U/LAspartate aminotransferase160 U/LCreatinine1.2 mg/dL (106.1 μmol/L)Fecal occult blood testNegativeA chest radiograph is normal and abdominal films show nondilated bowel loops with no free air.In addition to discontinuing the ipilimumab and providing supportive care, which of the following is the most appropriate next step in treatment?A. Broad-spectrum intravenous antibioticsB. Granulocyte-macrophage colony-stimulating factorC. High-dose intravenous glucocorticoidsD. ObservationCorrect AnswerC. High-dose intravenous glucocorticoidsEducational ObjectiveManage ipilimumab-induced toxicity.CritiqueInitiation of high-dose intravenous glucocorticoids and aggressive supportive care in addition to discontinuing the offending medication is the most appropriate treatment for this patient with ipilimumab toxicity with severe diarrhea and evidence of autoimmune hepatitis. Ipilimumab is a new class of antineoplastic therapy that inhibits the function of T-cell checkpoint receptors (ipilimumab or PD-1 and PD-L1 inhibitors), thereby enhancing the function of the immune system and inducing remissions in patients with various solid tumors, particularly metastatic melanoma. However, T-cell checkpoint inhibitors also can cause many potentially permanent and life-threatening organ toxicities that are autoimmune-mediated based on their enhancement of immune function. These include dermatologic (rash, mucositis), gastrointestinal (diarrhea, colitis), liver (autoimmune hepatitis), and endocrine (hypothalamic/pituitary, thyroid, and adrenal insufficiency). Other organ involvement (eye, kidney, hematologic, pulmonary, and neurologic) has also been reported. Because the toxicity results from triggering an exaggerated immune response, treatment of these toxicities involves removing the causative agent and providing immunosuppression, preferably with high-dose glucocorticoids due to their nonspecific immune-suppressing effects and rapid onset of action. Recognition of the autoimmune effect of the treatment is critical since the autoimmune-triggered toxicity from this class of medications can be fatal if immunosuppressive therapy is delayed.Because the mechanism of toxicity is not directly related to leukopenia and this patient has a normal leukocyte count with no objective evidence of infection, broad-spectrum antibiotics are not indicated, and delayed recognition of the drug-related syndrome from treatment of possible bacterial infection could be detrimental.Similarly, because the toxicity of T-cell checkpoint inhibitors is not due to leukopenia, treatment with growth factors, such as granulocyte-macrophage colony-stimulating factor, does not have a role in either the prevention or treatment of complications associated with this class of drugs.Because rapid immunosuppression may reverse the severe autoimmune reactions triggered by ipilimumab, discontinuation of the medication and supportive care alone is inadequate therapy for this patient.Key PointPatients with acute ipilimumab toxicity should receive fluid replacement and immediate glucocorticoid therapy to reverse the damage this agent can cause; delay in treatment can be fatal.BibliographyWeber JS, O’Day S, Urba W, et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 2008 Dec 20;26(36):5950-6.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 16 January 2018Volume 168, Issue 2Page: ED2KeywordsAntibioticsBlood pressureDiarrheaGraduate medical educationGranulocyte macrophage colony stimulating factorMelanomaPregnancyStatinsToxicityVomiting ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...