Jul 20, 2018

Redox revisited

The story

Emmaus Medical slapped a $40,000 yearly price tag on the amino acid it supplies to patients with sickle cell anemia. Here's a long-awaited breakdown of the evidence.

The basics

You've tried your best to forget, but we'll remind you that the NAD+/NADH ratio is key to maintaining redox balance in red blood cells (RBCs). Sickle RBCs live under a constant oxidative stress that researchers think serves as a trigger point for vasoocclusive crises (VOC). That's where glutamine can help: the amino acid replenishes NAD+ to fight excess oxidation. The FDA approved L-glutamine (brand name Endari) in July 2017 for sickle cell patients ages 5 and up – the first approval for sickle cell disease in over 20 years – but the final phase 3 trial results have only now become available.

The study

Weight-based L-glutamine powder reduced VOC by 25% compared to placebo in a yearlong RCT of 280 patients with sickle cell anemia and a history of 2 or more pain crises. The numbers favored L-glutamine across the board, as the treatment group had fewer pain crises (median 3 vs. 4), fewer hospitalizations (median 2 vs. 3), fewer episodes of acute chest syndrome, and a trend towards fewer ED visits. The study included patients both on and off old-standby hydroxyurea, inviting the use of combination therapy.

The takeaway

It's hard to put the sticker price aside when a quick Google search shows jars of L-glutamine available for <$20. But the amino acid is a low-risk med with a striking clinical impact, and basically everyone with sickle cell anemia is a candidate for treatment.  

Say it on rounds

When your PPD stays negative against all odds

You're less reactive than you think, and so are the almost 95% of patients who report a penicillin allergy but are actually tolerant upon formal allergy evaluation. A population-based matched cohort study of a large British health database found that outpatients with a reported penicillin allergy were 70% more likely to develop MRSA infection and 25% more likely to get C. diff than matched controls. Allergy patients were much more likely to receive broad spectrum β-lactam alternatives, which accounted for a significant percentage of the excess MRSA risk.

When you reach for Go-Lytely at the first sign of constipation

The big guns can be tempting. In a proof-of-concept trial in Norway, 21 patients with primary C. diff infection were more likely to achieve primary or secondary clinical cure with fecal micobiota transplant (78%) than oral metronidazole (45%), though the difference was not statistically significant in this preliminary correspondence. Expect to see more studies looking for optimal upfront treatment strategies for the notoriously recurrent bug. Oh, and keep in mind that the most recent IDSA guidelines call for PO vancomycin instead of metronidazole for upfront C. diff treatment.
NEJM Corres

When even you don't understand your patient's coumadin dosing schedule

Initial trials of novel oral anticoagulants (NOACs) excluded patients with end stage renal disease (ESRD), so the meds aren't used often in this population. A retrospective cohort of 25,000 Medicare beneficiaries with atrial fibrillation and ESRD on dialysis found that those on apixaban were less likely to have a stroke or experience major bleeding complications than patients on warfarin. The study is among the best evidence to date that NOACs are an appropriate choice in ESRD patients.

Brush up


Not everyone can blame their mental breaks on their black weekend. Psychosis is the inability to distinguish internal experiences from external reality. Look for hallucinations, disorganized thought, and delusions. Disorders are classified as either idiopathic (e.g. schizophrenia), secondary to a medical condition (CNS lupus), or toxic (substance abuse). When able, treat or reverse an underlying cause. Antipsychotics are standard treatment for idiopathic disorders, though there is a growing role for psychosocial treatment.

What's the evidence

For ED management of acute psychosis? Several agents are effective, and your ED probably has it's own favorite. A 2010 study of acute psychosis in Taiwan found no difference in 24-hour outcomes for 42 agitated patients with acute psychosis treated with intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution. The olanzapine formulations appeared to have quicker onset than IM haloperidol. 

What your radiology friends are talking about

Life's hard in black and white. A new X-Ray technique makes 3D images available in color.
"I use the app to scroll recent cards trials and catch up on things I've missed"
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