Jun 16, 2017

Direct action

The story

Seeing your just-discharged patient in the ED leaves you wondering what you did wrong. Chronic hep C patients who failed treatment feel the same way, but new research offers a second chance.

The background

Like the worst days of your intern year, treatment for chronic hepatitis C (HCV) was marginally effective and poorly tolerated. But 2006 marked a shift in treatment paradigm from difficult ribavirin and PEG-interferon regimens to much better direct-acting antiviral agents (DAAs). And though treatment with DAA combo pills has led to a sustained viralogic response (SVR) in over 90% of patients regardless of HCV genotype, disease stage, or treatment history, those who fail are often left without treatment options.

The study

Two multinational RCTs evaluated a three-drug combo regimen in patients with chronic HCV who did not respond to initial DAA treatment regimens. The trials included the sickest of the sick: almost half of the patients had cirrhosis, and many had induced genetic resistance to DAAs from prior therapy. The 12-week treatment regimen with sofosbuvir, vepatasvir and voxilaprevir achieved SVR rates of 96% and 98% of patients in the two trials. Headache and GI symptoms were notable adverse effects.

The takeaway

The superstar results suggest that the three-drug combo could eliminate much of the burden of refractory HCV, but cost and access will be significant hurdles.

Say it on rounds

When the end-of-the-academic-year celebration calls for one more round 

Probably a good idea. But be aware that a 30-year observational cohort study of adults in the UK found that moderate levels of alcohol consumption (8 - 12 drinks / week) were associated with adverse brain outcomes, including hippocampal atrophy. A dose-dependent relationship was seen between consumption and atrophy, with the highest consumers at highest risk. And while previous studies suggested that small amounts of alcohol had protective cognitive effects over abstinence, this study failed to show a protective effect for light (1 - 7 drinks / week) drinking.

When your clinic patients can't cut out the orange juice

Maybe they're on to something. Vitamin C levels are low or undetectable in severe sepsis, and a retrospective before-after study of 94 septic patients found that treatment with IV vitamin C, hydrocortisone, and thiamine reduced mortality by 75% compared to usual care (40% vs 9%, respectively). The treatment group had lower SOFA scores than the usual care group and was able to be weaned from vasopressors more quickly. The study's whopping effect size means you'll likely see larger, randomized studies soon.

When your list is blown up with C. diff

Isolation gowns are stuffy in the summer. A retrospective cohort study of 1,500 adult inpatients given antibiotics found that 20% of the patients experienced at least 1 antibiotic-associated adverse drug event (ADE). About 5% of patients developed C. diff infection within 90 days, and about 6% of patients developed infection with a multi-drug resistant organism. One fifth of the total ADEs were from situations where antibiotics were not clinically indicated.
JAMA Int Med

Brush up

Strongyloides stercoralis infection

Think of Strongyloidiasis in patients from the tropics with eosinophilia. Infection is often asymptomatic, and the parasitic nematode can remain quiescent indefinitely. The stakes are higher for the immunosuppresed, who are at high risk for the life-threatening hyperinfection syndrome. Symptoms include a pruritic purpuric rash followed by fever, hemoptysis and GI symptoms. Order serum Strongyloides serologies to evaluate, since stool microscopy has low sensitivity.

What's the evidence

For ivermectin treatment in chronic Strongyloides infection? A 2011 prospective RCT of 90 patients found that single and double dose regimens of ivermectin were more effective at eradicating infection than a 7-day course of albendazole. Parasitological cure rates were 97% for double dose ivermectin given two weeks apart, 93% for single dose ivermectin, and 63% for albendazole in the modified intention-to-treat analysis

What your Orange County friends are talking about

Sometimes fake tanning sprays just aren't enough, so thank science for a new melanin-producing drug that's in the early development pipeline. Here's a pic of a skin sample after drug treatment (far right box).

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