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November 4, 2014 Issue

Clinical Practice Points

Medical Knowledge

Cost-Effectiveness of Allopurinol and Febuxostat for the Management of Gout

Gout is the most common inflammatory arthritis in the United States, but previous cost-effectiveness analyses of febuxostat therapy did not include comparisons with escalating doses of allopurinol. This study found that allopurinol single therapy is cost-saving compared with no treatment, and dose-escalation allopurinol–febuxostat sequential therapy is cost-effective.

Use this study to:

  • Start a teaching session with a multiple-choice question. We’ve provided one below.
  • Use In The Clinic: Gout and ACP Smart Medicine: Gout to help prepare a teaching session. Use the pictures of tophaceous gout, urate crystals, and more. Look in the “Figures” section of ACP Smart Medicine.
  • Ask how a diagnosis of gout is made. What tests should be ordered? Should uric acid levels be followed?
  • Ask how to treat an acute flare of gout. When should chronic therapy be considered, and what medications should be used?

Medical Knowledge

Pharmacologic Interventions for Painful Diabetic Neuropathy. An Umbrella Systematic Review and Comparative Effectiveness Network Meta-analysis

Multiple treatments for painful diabetic peripheral neuropathy are available, but evidence-based guidance about the comparative effectiveness of these treatment options is lacking. Although this study found that several medications are effective for short-term management of painful diabetic neuropathy, their comparative effectiveness remains unclear.

Use this study to:

  • Ask your learners whether they examine their diabetic patients’ feet and perform a monofilament examination? Do they know how? Consider demonstrating such an examination at the bedside.
  • Ask how your learners manage their patients’ painful peripheral neuropathy.
  • Ask what education they provide their diabetic patients regarding foot care? When do they refer patients to podiatry?
  • Log on to answer the multiple-choice question provided with this paper to earn CME for yourself.

Clinical Guideline

Medical Knowledge

Dietary and Pharmacologic Management to Prevent Recurrent Nephrolithiasis in Adults: A Clinical Practice Guideline From the American College of Physicians

This guideline recommends managing patients with recurrent nephrolithiasis with increased fluid intake spread throughout the day to achieve at least 2 L of urine per day to prevent recurrent nephrolithiasis. If increased fluid intake fails to reduce stone formation, pharmacologic monotherapy with a thiazide diuretic, citrate, or allopurinol is recommended.

Use this guideline to:

  • Ask what diagnostic evaluation is appropriate in a patient presenting with acute nephrolithiasis. How is an acute episode managed? Ask what are the possible complications?
  • Review what this guideline recommends be done to prevent recurrences.
  • The guideline committee found there was insufficient evidence that evaluation of stone composition results in improved care. What are the different types of stones? Does knowing the type alter care? What other tests (e.g., blood or urine) are often sent to evaluate such patients? What do the results mean? How, if at all, do they alter what you do?

Medical Knowledge
Patient Care
In the Clinic

Obstructive Sleep Apnea

This eminently practical review discusses whom to screen, what to look for in a sleep study report, and how to troubleshoot patients’ problems with adherence to CPAP therapy.

Use this review to:

  • Ask your learners what symptoms should prompt consideration of sleep apnea. The presence of which other diseases might prompt asking about symptoms of sleep apnea? Which professions are at high risk for harm if sleep apnea is untreated?
  • Ask how to assess sleepiness? Aren’t we all sleepy? What’s different about a patient with sleep apnea?
  • Ask what retrognathia is. Review the Mallampati oropharynx classification—a figure is provided in the review.
  • Invite a sleep specialist to review the results of a sleep study—look at the waveforms and see how they are interpreted. Ask the expert to explain how she uses the apnea–hypopnea index, sleep latency, and other reported variables in practice.
  • Download the already-prepared teaching slides to help with your session.
  • Start and then split up a teaching session with the multiple-choice questions provided. Sign in and enter your answers to claim CME!

Humanism and Professionalism

Medical Knowledge
Interpersonal and Communication Skills

On Being a Doctor: The Forever War

In this haunting account of his journey through tours of duty in Iraq, medical school, and residency training, Dr. Boyce shares the terror of his isolation and emotional pain and how medical providers never asked about them.

Use this essay to:

  • Listen to an audio recording, read by Annals Associate Editor for On Being a Doctor, Dr. Michael LaCombe.
  • Ask your learners if they ask patients who are veterans specifically about emotional symptoms? Should they?
  • Use this essay to start a teaching session on the Care of Returning Military Personnel. Use the recent In The Clinic review on this topic to help prepare. Review what programs are in place to prevent disease and disability in returning military personnel. How common is PTSD? How is it managed? These and other key questions are answered succinctly in the review.

Other Resources From ACP


High Value Care Coordination Toolkit

These freely available materials feature resources to improve referrals and care coordination between primary care physicians and specialists, eliminate waste and duplicative care, and create more efficiency in care delivery. Take a look. Use the forms to help teach your learners how to best refer a patient for consultation. What information should be provided? How do you best coordinate the care provided by a primary care physician and consultants? Find answers here to help improve patient care.


A 62-year-old man is evaluated for a 5-year history of gout. He currently experiences approximately four attacks per year. His most recent attack was 3 weeks ago; at that time, he was started on daily colchicine. Six months ago, the patient was diagnosed with granulomatosis with polyangiitis; he was initially treated with prednisone and cyclophosphamide and was subsequently switched to azathioprine as a maintenance therapy. He has no other pertinent personal medical history.

On physical examination, temperature is 36.9 °C (98.5 °F), blood pressure is 117/72 mm Hg, pulse rate is 72/min, and respiration rate is 15/min. BMI is 27. The remainder of the examination is normal.

Laboratory studies reveal normal complete blood count and serum electrolyte levels; erythrocyte sedimentation rate is 23 mm/h, and serum uric acid level is 8.7 mg/dL (0.51 mmol/L). Estimated glomerular filtration rate is within normal range. 24-Hour urine collection findings are consistent with uric acid underexcretion.

Which of the following is the most appropriate treatment?

A. Allopurinol
B. Febuxostat
C. Pegloticase
D. Probenecid

Key Point
Allopurinol and febuxostat are contraindicated in the setting of azathioprine.

Educational Objective
Manage azathioprine drug-drug interactions.

Treatment with probenecid is indicated for this patient. Probenecid promotes renal urate excretion and is efficacious in patients who underexcrete uric acid (documented by a 24-hour urine collection) in the setting of a normal estimated glomerular filtration rate (GFR). (Its efficacy is limited in patients with significant decreases of estimated GFR.) Probenecid may increase the risk of kidney stones; therefore, patients taking probenecid must hydrate aggressively and may need to alkalinize their urine, and the drug should be used with caution in patients at high risk for stones (for example, a history of stones or tophaceous gout). This patient has frequent gout attacks in the setting of hyperuricemia and requires urate-lowering therapy. In this setting, probenecid would be both effective and compatible with this patient's azathioprine treatment for granulomatosis with polyangiitis.

Allopurinol and febuxostat each lower serum urate by inhibiting xanthine oxidase, an enzyme that converts xanthine to urate. Because azathioprine's active metabolite (6-mercaptopurine) is also metabolized by xanthine oxidase, both allopurinol and febuxostat increase the risk of azathioprine toxicity and are contraindicated in the setting of azathioprine use.

This question is derived from MKSAP® 16, the Medical Knowledge Self-Assessment Program.

From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Program Director in Internal Medicine, Thomas Jefferson University.


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