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Annals for Educators - 17 March 2020.
Annals of Internal Medicine ( IF 19.6 ) Pub Date : 2020-03-17 , DOI: 10.7326/awed202003170 Darren B. Taichman
中文翻译：
教育工作者年鉴-2020年3月17日。
更新日期：2020-03-19
Annals of Internal Medicine ( IF 19.6 ) Pub Date : 2020-03-17 , DOI: 10.7326/awed202003170 Darren B. Taichman
Clinical Practice Points
Adverse Effects of Low-Dose Methotrexate. A Randomized Trial
Although low-dose methotrexate is commonly used for the treatment of rheumatic diseases, data regarding potential adverse events are limited. This article reports the results of a rigorous, prospective evaluation of adverse events occurring with the use of low-dose methotrexate in a randomized, placebo-controlled trial.
Use this study to:
Start a teaching session with a multiple-choice question. We've provided one below!
Ask your learners whether any of their patients are taking methotrexate. Who prescribed it? For what indication?
How does methotrexate work? Why is folic acid prescribed with it?
Ask your learners to list potential side effects of methotrexate. How often do they occur? Are they dose-dependent? How is methotrexate therapy monitored?
Review the results of this study. Are they surprising? Reassuring?
What are the implications of the study participants having to complete an active “run-in” period? How does this affect our interpretation of the results?
Pharmacotherapy for the Treatment of Cannabis Use Disorder. A Systematic Review
Among regular users, cannabis may lead to physiologic dependence with withdrawal symptoms, but currently no pharmacotherapies have been approved by the U.S. Food and Drug Administration for treating cannabis use disorder (CUD). This systematic review evaluates available randomized trials of pharmacologic therapies to treat CUD in adults and adolescents.
Use this study to:
Ask your learners how acute cannabis intoxication may present. Use the information in DynaMed: Cannabis Use, a benefit of your ACP membership.
How is CUD defined? What are the potential symptoms? The authors address this in the paper's introduction and discussion.
What therapeutic approaches are used for CUD? What did this study find regarding their benefits and risks?
What were the limitations of the studies the authors evaluated? How might high rates of attrition bias the results of a clinical trial?
Physical Examination Pearls
The Hamman Sign: A Case Report With Audio Recording
This case report describes the presentation and evaluation of a patient with abnormal sounds in his chest—and includes an audio recording for teaching!
Use this report to:
Ask your learners if they know what the Hamman sign is.
With what entities is it associated?
Play the recording of the chest sounds to your learners.
Humanism and Professionalism
On Being a Doctor: On Agitation
Describing her experiences facing an agitated patient, Dr. McCann reflects, “So many of the emotions that arise when a patient is agitated or upset can feel utterly impermissible, antithetical to what it means to be a good health care provider. Yet, there they are, deep seams coursing through the everyday whether we name and meet them or not.”
Use this essay to:
Listen to an audio recording, read by Dr. Michael LaCombe.
Ask your learners to describe their encounters with acutely agitated patients. Have they felt personally threatened? Have they been scared?
What should be done when a patient is a threat to themselves or others? Do your learners know what to do?
Are we expected to put ourselves in harm's way?
Dr. McCann believes it is better to “meet” our “impermissible” emotions in such situations. What are they? Why is it better to “meet” them?
A History Lesson
Annals for Hospitalists Inpatient Notes - Hospital Wards
Dr. Howell's short and engaging essay discusses why hospitals used to have wards, why they disappeared, and how our profession has changed with this evolution.
Use this essay to:
Ask your learners what is meant by “the wards.” Have any of them seen a large, open hospital ward with multiple patient beds?
Do your learners agree with the author that the demise of wards has limited our interaction with nursing colleagues? Can your learners propose changes to current practice to regain some of the prior benefits of practicing on wards?
MKSAP 18 Question 1
A 67-year-old woman is evaluated for a 3-year history of severe rheumatoid arthritis. She had an inadequate response to methotrexate and low-dose prednisone. She responded well to the addition of infliximab, but eventually the drug lost effect and she required a change in biologic therapy. She has done well with tocilizumab and methotrexate over the past year. She notes several months of prominent fatigue. History is also significant for type 2 diabetes mellitus, hypertension, and hyperlipidemia. Current medications are methotrexate, folic acid, tocilizumab, basal insulin, lisinopril, metoprolol, atorvastatin, ibuprofen, and omeprazole.
On physical examination, vital signs are normal. Joint examination reveals no swollen or tender joints. The remainder of the physical examination is normal.
Laboratory studies:
| Hemoglobin | 9.3 g/dL (93 g/L) |
| Leukocyte count | 5600/µL (5.6 × 109/L) |
| Mean corpuscular volume | 111 fL |
| Platelet count | 330,000/µL (330 × 109/L) |
| Hemoglobin | 9.3 g/dL (93 g/L) |
| Leukocyte count | 5600/µL (5.6 × 109/L) |
| Mean corpuscular volume | 111 fL |
| Platelet count | 330,000/µL (330 × 109/L) |
Which of the following is the most likely cause of the anemia?
A. Inflammation
B. Iron deficiency
C. Methotrexate
D. Tocilizumab
Correct Answer
C. Methotrexate
Educational Objective
Diagnose methotrexate-induced anemia.
Critique
The most likely diagnosis is methotrexate-induced anemia. Methotrexate can cause stomatitis, hepatic inflammation and fibrosis, and myelotoxicity, including megaloblastic anemia and pancytopenia. Folic acid supplementation is mandatory in all patients receiving methotrexate and can prevent the development of stomatitis and hepatotoxicity (as measured by elevated aminotransferase levels). Hematologic toxicity, however, can occur even with folic acid supplementation. In this patient, a rise in mean corpuscular volume (MCV) indicates a likely megaloblastic anemia, and methotrexate is the likely cause. Guidelines from the American College of Rheumatology recommend periodic monitoring of the complete blood count every 4 weeks during the first 3 months of therapy, every 8 to 12 weeks from 3 to 6 months, and every 8 to 12 weeks thereafter.
Inflammatory anemia (anemia of chronic disease) is a common manifestation of rheumatoid arthritis and is usually a mild, normocytic anemia. Most patients experience symptoms related to their underlying disease rather than the anemia. Inflammatory anemia would not present with this degree of anemia or macrocytosis.
Typical features of iron deficiency are identical to those of any symptomatic anemia but may be subtle owing to an insidious onset of the condition. Headache and pica (craving for typically undesirable items such as ice, dirt, clay, paper, and laundry starch) are frequently associated symptoms; other less common symptoms include restless legs syndrome and hair loss. The hallmark of iron deficiency is a microcytic hypochromic anemia. However, this is usually only seen in advanced iron deficiency, and anemia tends to precede morphologic changes in the cells. The presence of macrocytosis makes iron deficiency unlikely.
Tocilizumab is not associated with a macrocytic anemia. Through its anti-inflammatory properties, it may decrease the likelihood of inflammatory-induced anemia in patients with rheumatoid arthritis.
Key Point
Methotrexate use can result in a megaloblastic anemia or pancytopenia; periodic monitoring of the complete blood count is recommended.
Bibliography
Shea B, Swinden MV, Ghogomu ET, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol. 2014;41:1049-60. doi:10.3899/jrheum.130738
MKSAP 18 Question 2
A 25-year-old woman is hospitalized for a 4-week history of swelling of the legs, weight gain, and shortness of breath on exertion. She was diagnosed with systemic lupus erythematosus 1 year ago when she presented with polyarthritis, rash, and alopecia. She was initially treated with hydroxychloroquine and prednisone with a good response.
On physical examination, blood pressure is 142/96 mm Hg; other vital signs are normal. There is pitting edema of the lower extremities extending to the knees. The remainder of the physical examination is normal.
Laboratory studies:
| Erythrocyte sedimentation rate | 68 mm/h |
| Hematocrit | 38% |
| Complements (C3 and C4) | Low |
| Creatinine | 1.0 mg/dL (88.4 µmol/L) |
| Anti-Smith antibodies | Positive |
| Anti–double-stranded DNA antibodies | Positive |
| Urinalysis | 3+ protein; no erythrocytes; no leukocytes; no casts |
| Urine protein | 6000 mg/24 h |
| Erythrocyte sedimentation rate | 68 mm/h |
| Hematocrit | 38% |
| Complements (C3 and C4) | Low |
| Creatinine | 1.0 mg/dL (88.4 µmol/L) |
| Anti-Smith antibodies | Positive |
| Anti–double-stranded DNA antibodies | Positive |
| Urinalysis | 3+ protein; no erythrocytes; no leukocytes; no casts |
| Urine protein | 6000 mg/24 h |
The patient is started on prednisone, along with diuretics and an ACE inhibitor.
Kidney biopsy results show class V (membranous) lupus nephritis with absent chronicity and mild activity.
Which of the following is the most appropriate treatment of the kidney disease?
A. Adalimumab
B. Belimumab
C. Cyclophosphamide
D. Methotrexate
E. Mycophenolate mofetil
Correct Answer
E. Mycophenolate mofetil
Educational Objective
Treat class V (membranous) lupus nephritis.
Critique
Mycophenolate mofetil is the most appropriate treatment of this patient's kidney disease. Classification of lupus nephritis is based on findings by light microscopy, electron microscopy, and immunofluorescence. This patient with recently diagnosed systemic lupus erythematosus (SLE) now presents with proteinuria likely due to lupus nephritis (likely class V, membranous). Guidelines recommend aggressive therapy with immunosuppressives for significant kidney involvement. A number of immunosuppressive therapies are beneficial in the treatment of SLE nephritis, including mycophenolate mofetil, cyclophosphamide, azathioprine, and rituximab. In the treatment of isolated class V lupus nephritis, especially without kidney dysfunction, mycophenolate mofetil is the most appropriate initial immunosuppressive therapy based on the guideline recommendations. Importantly, mycophenolate mofetil is teratogenic and has been associated with fetal harm and death; it must be stopped 3 months before a planned pregnancy.
Adalimumab has not been shown to be effective in lupus nephritis and may potentially worsen the disease based on animal data.
Belimumab may be considered in patients with continued SLE activity after standard therapy has been tried and found to be ineffective. Its role in the treatment of lupus nephritis continues to evolve but is currently not well defined. Its use in this patient should not be considered before having tried standard therapy.
Cyclophosphamide may be considered in this patient and used appropriately in patients with lupus nephritis but is not an appropriate first choice due to a higher rate of side effects compared with mycophenolate mofetil, as well as its effect on reducing fertility and premature menopause. Cyclophosphamide is typically reserved for severe active nephritis to induce remission, followed by mycophenolate mofetil or possibly azathioprine as maintenance therapy.
Methotrexate is not effective in lupus nephritis and may be associated with toxicity in a patient with kidney disease.
Key Point
Mycophenolate mofetil is the most appropriate initial immunosuppressive therapy in the treatment of isolated class V lupus nephritis, especially without kidney dysfunction.
Bibliography
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al; American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64:797-808. doi:10.1002/acr.21664
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中文翻译：
教育工作者年鉴-2020年3月17日。
临床实践要点
低剂量甲氨蝶呤的不良反应。随机试验
尽管小剂量甲氨蝶呤通常用于治疗风湿病，但有关潜在不良事件的数据仍然有限。本文报告了一项随机，安慰剂对照试验中对使用低剂量甲氨蝶呤发生的不良事件进行严格，前瞻性评估的结果。
使用此研究可以：
用选择题开始教学课程。我们在下面提供了一个！
询问您的学习者，他们的患者是否正在服用甲氨蝶呤。谁开的？有什么指示？
甲氨蝶呤如何工作？为什么要处方叶酸？
让您的学习者列出甲氨蝶呤的潜在副作用。它们多久发生一次？他们是剂量依赖性的吗？如何监测甲氨蝶呤治疗？
查看本研究的结果。他们感到惊讶吗？放心吗
研究参与者必须完成一个活跃的“磨合”期有什么含义？这如何影响我们对结果的解释？
药物治疗大麻使用障碍。系统评价
在普通用户中，大麻可能会导致生理依赖性，并伴有戒断症状，但目前美国食品药品监督管理局尚未批准任何药物疗法可用于治疗大麻使用障碍（CUD）。该系统评价评估了可用于治疗成人和青少年CUD的药物治疗的随机试验。
使用此研究可以：
问你的学习者可能会出现急性大麻中毒的情况。使用DynaMed：大麻使用中的信息，这是ACP成员资格的一项好处。
如何定义CUD？有哪些潜在的症状？作者在论文的介绍和讨论中解决了这一问题。
CUD使用什么治疗方法？这项研究发现了哪些好处和风险？
作者评估的研究有哪些局限性？高流失率会如何影响临床试验的结果？
体检珍珠
哈曼标志：带有录音的病例报告
该病例报告描述了患者的胸部声音异常的表现和评估，并包括用于教学的录音！
使用此报告可以：
询问您的学习者是否知道哈曼标志是什么。
它与哪些实体相关联？
向您的学习者播放胸部声音的录音。
人文主义和专业精神
成为医生：激动
麦肯医生在描述自己面对躁动不安的病人时的经历时说：“当患者烦躁不安或心烦意乱时，所产生的许多情绪可能完全让人无法接受，这与成为一名好的医疗保健提供者是相反的。然而，不管我们是否命名和遇见它们，它们之间每天都有深处的缝隙。”
使用本文来：
收听录音，由Michael LaCombe博士朗读。
要求您的学习者描述他们与急躁患者的相遇。他们是否感到了个人威胁？他们害怕了吗？
当患者对自己或他人构成威胁时，该怎么办？您的学习者知道该怎么做吗？
我们是否应该以伤害自己的方式对待自己？
麦肯博士认为，在这种情况下最好是“满足”我们“不允许的”情绪。这些是什么？为什么“见面”会更好？
历史课
医院住院病人年鉴-病房
豪威尔博士的简短而引人入胜的文章讨论了为什么医院曾经设有病房，为何失踪以及我们的职业随着这种发展而发生了怎样的变化。
使用本文来：
问您的学习者“病房”的含义。他们中有没有人看到一个宽敞的，开放的，有多个病床的医院病房？
您的学习者是否同意作者的观点，即病房的消亡限制了我们与护理同事之间的互动？您的学习者是否可以提出对当前实践的建议，以重新获得在病房进行实践的某些先前的好处？
MKSAP 18问题1
对一名67岁妇女的严重类风湿关节炎病史进行了3年评估。她对甲氨蝶呤和小剂量泼尼松反应不佳。她对英夫利昔单抗的添加反应良好，但最终药物失去了作用，她需要改变生物疗法。过去一年中，她在使用tocilizumab和甲氨蝶呤方面做得很好。她注意到几个月的明显疲劳。对于2型糖尿病，高血压和高脂血症，病史也很重要。当前的药物是甲氨蝶呤，叶酸，托珠单抗，基础胰岛素，赖诺普利，美托洛尔，阿托伐他汀，布洛芬和奥美拉唑。
经身体检查，生命体征正常。关节检查未发现关节肿胀或触痛。其余体检正常。
实验室研究：
| 血红蛋白 | 9.3克/分升（93克/升） |
| 白细胞计数 | 5600 / µL（5.6×10 9 /升） |
| 平均红细胞体积 | 111升 |
| 血小板计数 | 330,000 / µL（330×10 9 / L） |
| 血红蛋白 | 9.3克/分升（93克/升） |
| 白细胞计数 | 5600 / µL（5.6×10 9 /升） |
| 平均红细胞体积 | 111升 |
| 血小板计数 | 330,000 / µL（330×10 9 / L） |
以下哪一项是最可能导致贫血的原因？
A.发炎
B.铁缺乏症
甲氨蝶呤
D.托珠单抗
正确答案
甲氨蝶呤
教育目标
诊断甲氨蝶呤引起的贫血。
批判
最可能的诊断是甲氨蝶呤引起的贫血。甲氨蝶呤可引起口腔炎，肝炎和纤维化以及骨髓毒性，包括巨幼细胞性贫血和全血细胞减少。所有接受甲氨蝶呤的患者都必须补充叶酸，并且可以预防口腔炎的发展和肝毒性（以转氨酶水平升高为衡量标准）。但是，即使补充叶酸也会发生血液学毒性。在该患者中，平均红细胞体积（MCV）升高表明可能是巨幼细胞性贫血，而甲氨蝶呤可能是原因。美国风湿病学会的指南建议在治疗的前3个月中每4周，3到6个月中每8到12周以及此后每8到12周定期监测全血细胞计数。
炎性贫血（慢性疾病性贫血）是类风湿关节炎的常见表现，通常是轻度的正常血红细胞性贫血。大多数患者经历的症状与其潜在疾病有关，而不是与贫血有关。这种程度的贫血或巨噬细胞不会出现炎症性贫血。
铁缺乏症的典型特征与任何症状性贫血的特征相同，但由于隐匿性疾病发作而可能微妙。头痛和异食癖（渴望冰，污垢，黏土，纸张和洗衣粉等通常不受欢迎的食物）经常伴有症状；其他较不常见的症状包括腿不安综合症和脱发。铁缺乏症的标志是小细胞性低铬性贫血。但是，这通常仅在晚期铁缺乏症中才能见到，贫血往往先于细胞形态变化。巨噬细胞的存在使铁缺乏成为不可能。
托珠单抗与大细胞性贫血无关。通过其抗炎特性，它可以降低类风湿关节炎患者因炎性贫血的可能性。
关键
使用甲氨蝶呤可能导致巨幼细胞性贫血或全血细胞减少。建议定期监测全血细胞计数。
参考书目
Shea B，Swinden MV，Ghogomu ET，Ortiz Z，Katchamart W，Rader T等。叶酸和亚叶酸可降低氨甲蝶呤类风湿关节炎患者的副作用。J风湿病。2014; 41：1049-60。doi：10.3899 / jrheum.130738
MKSAP 18问题2
一名25岁的女性因腿部肿胀，体重增加和劳累时呼吸急促而住院了4周。1年前，她被诊断出患有系统性红斑狼疮，当时她患有多关节炎，皮疹和脱发。她最初接受羟氯喹和泼尼松治疗，反应良好。
经身体检查，血压为142/96毫米汞柱；其他生命体征正常。下肢出现点状水肿，延伸至膝盖。其余体检正常。
实验室研究：
| 红细胞沉降率 | 68毫米/小时 |
| 分血器 | 38％ |
| 补语（C3和C4） | 低 |
| 肌酐 | 1.0 mg / dL（88.4 µmol / L） |
| 抗史密斯抗体 | 正 |
| 抗双链DNA抗体 | 正 |
| 尿液分析 | 3+蛋白；没有红细胞；没有白细胞；没有演员 |
| 尿蛋白 | 6000毫克/ 24小时 |
| 红细胞沉降率 | 68毫米/小时 |
| 分血器 | 38％ |
| 补语（C3和C4） | 低 |
| 肌酐 | 1.0 mg / dL（88.4 µmol / L） |
| 抗史密斯抗体 | 正 |
| 抗双链DNA抗体 | 正 |
| 尿液分析 | 3+蛋白；没有红细胞；没有白细胞；没有演员 |
| 尿蛋白 | 6000毫克/ 24小时 |
患者开始使用泼尼松，利尿剂和ACE抑制剂。
肾脏活检结果显示，V类（膜性）狼疮性肾炎缺乏慢性病且活动轻微。
以下哪项是最合适的肾脏疾病治疗方法？
A.阿达木单抗
贝利木单抗
C.环磷酰胺
D.甲氨蝶呤
霉酚酸酯
正确答案
霉酚酸酯
教育目标
治疗V级（膜性）狼疮肾炎。
批判
霉酚酸酯是该患者肾脏疾病的最合适治疗方法。狼疮性肾炎的分类是基于光学显微镜，电子显微镜和免疫荧光的发现。这位最近被诊断为系统性红斑狼疮（SLE）的患者现在表现为蛋白尿，可能是由于狼疮性肾炎（可能是V级，膜性）引起的。指南建议采用免疫抑制剂进行积极治疗，以防止肾脏严重受累。许多免疫抑制疗法在治疗SLE肾炎中是有益的，包括霉酚酸酯，环磷酰胺，硫唑嘌呤和利妥昔单抗。在孤立的V类狼疮肾炎的治疗中，尤其是没有肾脏功能障碍的患者，根据指南的建议，霉酚酸酯是最合适的初始免疫抑制治疗。重要的是，霉酚酸酯具有致畸性，并与胎儿的伤害和死亡有关。必须在计划怀孕前三个月停止。
根据动物数据，尚未证明阿达木单抗对狼疮性肾炎有效，并可能使疾病恶化。
在尝试了标准治疗后发现贝立单抗仍具有持续的SLE活动的患者，可以认为贝立木单抗无效。它在治疗狼疮性肾炎中的作用继续发展，但目前尚不明确。在尝试标准疗法之前，不应考虑在该患者中使用它。
该患者可考虑使用环磷酰胺，并在狼疮性肾炎患者中适当使用环磷酰胺，但由于与霉酚酸酯相比，其副作用发生率更高，并且具有降低生育能力和更年期提前的作用，因此不是合适的首选。环磷酰胺通常保留用于严重的活动性肾炎以诱导缓解，然后再使用麦考酚酸酯或可能的硫唑嘌呤作为维持疗法。
甲氨蝶呤对狼疮性肾炎无效，可能与肾病患者的毒性有关。
关键
霉酚酸酯是治疗孤立的V类狼疮肾炎，尤其是无肾功能不全的最合适的初始免疫抑制疗法。
参考书目
Hahn BH，McMahon MA，Wilkinson A，Wallace WD，Daikh DI，Fitzgerald JD等；美国风湿病学院。美国风湿病学会筛查，治疗和管理狼疮性肾炎的指南。关节炎护理资源（Hoboken）。2012; 64：797-808。doi：10.1002 / acr.21664
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