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Dec 7, 2018

Back on track

The story

Your brain can do fancier things than dose diuretics during run-of-the-mill heart failure hospitalizations, but it's nice to stay in your comfort zone. Can an outpatient med shake up the routine?

The background

It's as tiring as it is tried and true: admit, diurese, repeat. Basic inpatient heart failure management hasn't changed in decades despite a slew of failed trials. The ideal med would unload the heart by dropping afterload, increasing salt excretion, and dampening sympathetic tone. Sacubitril-valsartan (Entresto) – an outpatient winner following 2014's PARADIGM-HF – mechanistically fits the bill, but inpatients were excluded from the landmark 2014 study. It was only a matter of time until the medication was put to the test on the wards.   

The study

PIONEER-HF compared sacubitril-valsartan to placebo in 880 patients admitted with acute decompensated heart failure (ADHF). The trial met its biomarker-driven primary outcome by reducing NT-proBNP levels compared to placebo after 8 weeks. More impressive were results from a prespecified clinical composite outcome: the rate of rehospitalization, death, or listing for transplant was 9% in the treatment group and 16% for placebo, a 45% relative risk reduction in the trial's brief intervention period. 
NEJM

The takeaway

Though longer-term follow-up will be watched closely, these results could very well be practice changing. Entresto supporters think that starting the med in the hospital will also prompt greater use in the outpatient setting.

Say it on rounds

When they run out of free drinks at applicant happy hour

We don't always believe that less is more, but there are exceptions. The HIGH trial compared standard oxygen delivery with high flow nasal cannula (HFNC) in 800 immunocompromised ICU patients with acute hypoxemic respiratory failure (AHRF). While the HFNC arm achieved higher oxygen saturation, there was no difference in 28-day mortality, need for intubation, or ICU length of stay between groups. The authors suggest that in immunocompromised patients – a group at increased risk for severe AHRF – treating the underlying cause is more pressing than optimizing O2 sat status.
JAMA

When the interpreter phone has you on indefinite hold

Global medicine has its share of challenges. And while CAR T-cell therapy works well when the lab is next door, incorporating the personalized treatment into the global supply chain presents all kinds of logistical hurdles. JULIET evaluated CAR-T therapy with tisagenlecleucel (Kymriah) in a phase 2 study of 90 patients with refractory DLBCL in 10 countries. After median follow-up of 14 months, best overall response rate was 52% and the rate of complete response was 40%. The therapy was successfully delivered to 4 continents with use of centralized manufacturing in what the authors call a real-world treatment scenario.
NEJM

When you sign up to moonlight after 27 hour call

You need to have your head checked, but do kids? The PECARN algorithm was designed to minimize unnecessary head CT use in academic pediatric EDs. Researchers evaluated the strategy in 250 children with closed-head injuries in a single-center community ED and found that after education and implementation of the algorithm, CT use in low-risk patients decreased from 22% to less than 1%. No significant traumatic brain injuries were missed. The authors plan to develop an electronic decision support tool and integrate it into the EMR. 
Acad Emerg Med

Brush up

Iron chelation

It’s a step or two removed from your day to day workflow, but iron chelation therapy is critical for transfusion-dependent patients. Chronic iron overload leads to cardiotoxicity like heart failure and arrhythmias, and before the advent of chelation therapy mean survival for these patients averaged about 15 years. Chelators bind to tissue iron and prompt excretion in the feces or urine. Available chelation agents include oral deserasirox and deferiprone or subcutaneous deferoxamine.

What's the evidence

Behind choice of iron chelator? A meta-analysis of 1,000 patients found that oral deferiprone led to greater improvement in left ventricular ejection fraction (EF) and endocrine dysfunction than subcutaneous deferoxamine. Combination therapy with both agents was superior to monotherapy in improving EF. Patients receiving chelation need to be monitored for neutropenia, agranulocytosis, and GI side effects. 

What your OB friends are talking about

The world’s first live birth from a deceased donor uterus transplant could provide a whole new avenue for treating uterine infertility. Read the case report here

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