Aug 16, 2019

New tricks

The story

If there are lessons to be learned from the hospital cafeteria, it's that there are always better ways to use what you have. Here's how new and improved antibodies are making headway in Ebola.

The background

About one-third of patients survive Ebola virus disease (EVD), so neutralizing antibodies are out there. The search to translate these antibodies into effective therapies has been underway since the 1995 outbreak in the Democratic Republic of the Congo (DRC). Hopes were high for ZMapp, a triple monoclonal antibody cocktail, during the West African epidemic of 2015, though a RCT failed to show a statistically significant survival benefit. The results were good enough, however, to allow ZMapp to be used as a control in new EVD clinical trials.

The breakthrough

PALM compared 3 novel drug candidates to ZMapp in 680 patients in the DRC. The trial was stopped early after 2 of the 3 new drugs were found to reduce mortality. Treatment with mAb114, an antibody that was isolated from survivors, and REGN-EB3, a mixture of 3 monoclonal antibodies engineered from mice, led to survival in about 70% of patients compared to about 50% of patients treated with ZMapp and the antiviral remdesivir. When treatments were given early after infection mortality plummeted to 6% for REGN-EB3 and 11% for mAb114. 

The takeaway

Press claims of a cure are a bit premature, but this is a stunning accomplishment for this highly lethal disease. The two treatments are expected to soon be put to use in the ongoing outbreak in the DRC.

Say it on rounds

When you wish that rounds stuck to schedule

Not happening, but take consolation in precise perioperative start and stop times for direct oral anticoagulants (DOACs). PAUSE evaluated a standardized protocol for DOAC interruption and resumption in 3,000 patients with a-fib undergoing elective surgery. Regimens were held for 1 day before and after surgery for low risk procedures and 2 days before and 2 - 3 days after high-risk procedures. Rates of thromboembolism (<1%) and major bleeding (<2%) were within the prespecified safety range.
JAMA Int Med

When you stopped trying to pronounce drug names years ago

Say it back: galcenezumab. The anti-CGRP antibody reduced the frequency of episodic cluster headaches compared to placebo with minimal adverse effects in a 100-patient RCT. This is the first use of the anti-CGRP drug class – which has seen much recent success in migraine prevention – in cluster headache, and galcenezumab is the first FDA-approved preventative med for the disorder. 

When the head-on-desk nap gives you pins and needles

You're onto something. A RCT of 400 Chinese patients with chronic stable angina found that 4 weeks of scheduled acupuncture treatments performed at points along the cardiac meridian reduced the frequency of self-reported angina attacks compared to non-cardiac acupoints, sham acupoints, and those not receiving acupuncture. On average, patients in the cardiac meridian group reported ~8 fewer attacks per week at the end of the study compared to their baseline attack frequency.
JAMA Int Med

Brush up

Subclinical hypothyroidism

Up to 10% of the population will screen positive for subclinical hypothyroidism (SH), and most patients will return to euthyroidism without clinical intervention. Look for serum thyroid hormone levels within the reference range with thyrotropin levels above the reference range. While generally asymptomatic, about 2 - 4% of patients with mild thyrotropin elevations will progress to overt hypothyroidism per year. Meta-analyses have linked SH to adverse cardiovascular outcomes, though the strength of these associations and whether treatment is warranted remains a subject of debate.

What's the evidence

For treatment of SH with thyroid supplementation? In general treatment has broadly fallen out of favor after 2017's TRUST trial found no evidence of benefit for levothryoxine therapy in 700 elderly patients with subclinical hypothyroidism. Consider treatment for young patients with markedly elevated thyrotropin levels, as this population is at high risk for progression to overt disease.

What your video game friends are talking about

A single-center study of hospitalized patients found that virtual reality immersion experiences reduced pain scores (and boredom?) compared to watching TV. Patients could choose from these VR experiences.

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