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Jun 21, 2019

In sequence

The story

Next-generation-sequencing (NGS) is a heavy hitter in the research world, but it hasn't yet made its way to your typical hospital shift. Genomics is reshaping how we find microbes in the CSF. 

The background

Even if your patients are lucky to be tapped now instead of with new interns on July 1st, there's no guarantee cerebrospinal fluid (CSF) will provide answers. The work up for acute meningoencephalitis fails to identify a causative organism in about half of patients. Extremely sensitive DNA analysis could help, and metagenomic NGS (mNGS) evaluates all microbial DNA – bacteria, viruses, fungi – in a single assay. The platform is expensive, and results need expert analysis in the form of clinical sequencing boards to help guide clinicians through the data. Is it ready for prime time? 

The study

PDAID looked at mNGS as a diagnosis and management tool on the wards. In a prospective study of 204 hospitalized patients with meningitis, mNGS of the CSF identified a causative organism in 13 patients where traditional clinical testing failed to reveal a source. Since only 57 study patients (28%) ultimately received a pathogen diagnosis, sequencing accounted for about 20% of microorganism finds. mNGS helped guide treatment in 7 of these 13 patients.
NEJM

The takeaway

Use of sequencing in routine clinical care seems like an inevitability, and mNGS data can be used for more than just diagnosis. Expect similar studies in other tissues soon.

Say it on rounds

When the ICU means black coffee on an empty stomach

The acid feels inevitable, but proton pump inhibitors don't have to be. A VA-based longitudinal cohort that tracked new PPI use in 200,000 veterans found a major risk of excess mortality compared to veterans given H2 blockers. PPIs prompted 45 excess deaths for every 1,000 treated patients, with associated excess mortality tied to cardiovascular disease and chronic kidney disease. Cumulative risk of harm increased with duration on treatment, and patients without a documented indication for acid suppression had worse outcomes.
BMJ

When you thought you had a special connection with the page operator

Sometimes you need a clean break, and so do sickled red blood cells in sickle cell disease (SCD). A phase 3 RCT of voxelotor – an oral med that inhibits hemoglobin S polymerization (see mechanism video) – in 274 SCD patients found that more patients in the treatment group (51% for the highest dose vs. 7% for placebo) saw their baseline hemoglobin increase by > 1 g/dL at 6 months. Voxelotor patients also saw a reduction in hemolysis, though there was no difference in vaso-occlusive crises between groups.
NEJM

When George Clooney never shows up in your ED

Your life is definitely not like TV. But new analysis suggests that adolescent suicides increased immediately after the release of the show 13 Reasons Why in March 2017. The 3 months following the show's release saw a 13% increase in suicides in the 10 - 19 age group in the context of a moving average suicide rate. The Netflix show, which sparked high ratings and intense commentary on social media, drew heavy criticism from suicide prevention groups for its portrayal of suicide.
JAMA Psych

Brush up

Primary hyperparathyroidism

Look to labs to find primary hyperparathyroidism (PHPT): start by working up what is often subclinical hypercalcemia, then watch for inappropriately normal or elevated parathyroid hormone levels. The symptomatic state of the disease characterized by the "Stones, Bones and Groans" of hypercalcemia is rare thanks to widespread testing. Parathyroid imaging studies have no role in diagnosis, and parathyroidectomy remains the only curative treatment. About 80% of cases are due to a solitary parathyroid adenoma.

What's the evidence

For fracture in PHPT? PHPT patients show evidence of bone loss on DEXA, and a 2009 case-control study of 150 postmenopausal women with sporadic PHPT and 300 healthy controls found an increase in the vertebral fracture event rate (25% vs. 4%) in PHPT patients. Fracture rate was higher for symptomatic patients than asymptomatic patients, and higher (28% vs. 11%) among those who met NIH criteria for parathyroidectomy than those who did not.   

What your MD/MBA friends are talking about

We’re a little late to the party, but we have to give a shout to Danielle Ofri for her excellent op-ed on the exploitation of professionalism and good will in medicine.

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