Someday, I’ll publish another article summary that doesn’t involve a conflict-of-interest skewering. I’m really not as angry as Rob Orman says I am. This article, at least, is directly relevant to the Emergency Department.
There’s been significant research into biomarkers for infectious/inflammatory processes, with the goal of identifying a sufficiently sensitive assay to use as a “rule-out” for serious infection. The goal is to use such an assay to prevent the overuse of antibiotics without increasing morbidity/mortality. This is a good thing.
Procalcitonin is the latest darling of pediatrics and intensive care units. However, to call the literature “inconclusive” is a bit of an understatement – which is why I was surprised to see an article in JAMA squarely endorsing procalcitonin-guided antibiotic-initiation strategies. After all, I’ve previously covered negative trials in this blog (pubmed, pubmed). However, these authors seem to have intentionally narrowed their trial selection to exclude these trials – and publish no methods regarding their systematic selection of articles.
The disclosures for all three authors includes “BRAHMS/Thermofisher”. Who is this, you might ask? Google points me to: http://www.procalcitonin.com – where BRAHMS/Thermofisher will sell you one of seven procalcitonin assays. JAMA, third-ranked medicine journal in Impact Factor, reduced to advertising masquerading as peer-reviewed science.
“Clinical Outcomes Associated With Procalcitonin Algorithms to Guide Antibiotic Therapy in Respiratory Tract Infections”http://www.ncbi.nlm.nih.gov/pubmed/23423417
Category: Screening
UTI: Yet Another Windmill?
Medicine is full of windmills re-imagined as dragons – and two of the most prominent voices of reason in Emergency Medicine are David Newman and Jerome Hoffman. This skeptical take on pediatric urinary tract infections is David Newman’s latest, which covers content reflective of his SMART EM podcast on the same topic.
The premise of his argument is rather straightforward:
- There’s substantial overlap between UTI and asymptomatic bacteruria, leading to overdiagnosis.
- Even when the diagnosis is correctly made, prompt treatment does not prevent complications.
The complications in question are urosepsis and renal scarring. Urosepsis, in David’s literature review only results from urinary tract infections from the otherwise immunosuppressed, or in infants with congenital anomalies. Renal scarring, purportedly from pyelonephritis, has little or controversial evidence in supporting antibiotic use from preventing it.
This will be published in an upcoming issue of Annals of Emergency Medicine.
“Pediatric Urinary Tract Infection: Does the Evidence Support Aggressively Pursuing the Diagnosis?”
www.ncbi.nlm.nih.gov/pubmed/23312370
Lactate – Is There Any Death It Doesn’t Predict?
Turns out – apparently, no!
Continuing the run on pulmonary embolism articles, we find that – in addition to all the things we know prognosticates increased mortality in PE patients – elevated plasma lactate levels also predict poor outcomes. This is generally unsurprising, because elevated lactate levels are associated with increased mortality, even in unselected ED patients. What is interesting, however, is that lactate levels >2 mmol/L were more associated with 30-day mortality than shock/hypotension, hypoxia, or right-ventricular dysfunction. It’s a small cohort, but it’s a reasonable finding, regardless.
However, what’s sort of odd regarding the Editor’s Summary for this article is that it specifically mentions the lactate level does not outperform a simplified pulmonary embolism severity index clinical tool. The “truth” is that an AUC of 0.84 is better than an AUC of 0.71 – but that (0.72 to 0.95) and (0.60 to 0.83) overlap. Rather than trash the lactic acid level compared with the PESI, it might have been more accurate to simply state the current study was underpowered to confirm the advantage of lactic acid over PESI, and further research is necessary.
Can you buy stock in lactate level assays? It’s clearly the new favorite all-purposes prognostication tool.
“Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism: The Thrombo-Embolism Lactate Outcome Study”
http://www.ncbi.nlm.nih.gov/pubmed/23306454
http://www.ncbi.nlm.nih.gov/pubmed/23306454
Inadequate “Overuse” Reduction Strategies
This study was featured in Academic Emergency Medicine as one of their CME articles – theoretically, an article with additional value presented with incentives to motivate a closer reading of the content. I don’t mean to imply this is somehow a bad article – but it’s just interesting to step back out of the tunnel vision of statistics and boggle at the inadequacy of the current state of medicine.
This is a prospective study of patients evaluated for pulmonary embolism attempting to evaluate how many patients were “inappropriately” scanned. This definition of “inappropriate” scanning was determined by patients who were either PERC negative or had low-risk Wells’ score followed by a negative d-Dimer. Overall, of 152 patients, 11.8% were ultimately diagnosed with PE. However, the authors state that application of the PERC rule might have eliminated 9.2% of these scans while Wells’/d-Dimer would have obviated 13.8%.
While I certainly don’t discount the beneficial effect of even small reductions in the number of individuals evaluated for pulmonary embolism, these are still terrible numbers. 90% of CT scans for PE are negative? And using these decision instruments gets us to ~75% negative scans? This would be comically wasteful performance and innovative performance improvement in any other industry.
We pretty clearly need to do better.
“Overuse of Computed Tomography Pulmonary Angiography in the Evaluation of Patients with Suspected Pulmonary Embolism in the Emergency Department”
www.ncbi.nlm.nih.gov/m/pubmed/23167851/
End-Tidal to Predict Operative Intervention in Trauma
In penetrating trauma, sometimes it’s very simple to predict operative intervention. However, sometimes, the perfusion states of our patients are less easy predict – vital signs frequently obfuscate the underlying clinical picture as the body compensates.
This is a prospective study that indirectly aims to validate end-tidal CO2 as a predictor of operative intervention in penetrating trauma by correlating it to serum lactate levels. And, as their primary outcome, these investigators observed a strong correlation between ETCO2 and lactate levels (R^2 = 0.74). For secondary endpoints – unsurprisingly, considering it was correlated with lactate – ETCO2 was also predictive of operative intervention. In fact, the authors report ETCO2 was more predictive of intervention than lactate, although it seems a little odd to significantly outperform lactate, given the strength of their linear correlation.
Compared with systolic blood pressure, the test performance characteristics essentially tell us what we already know: normal blood pressure isn’t helpful, low blood pressure is obviously helpful (98% specificity). Lactate and ETCO2 are more sensitive to hypoperfusion states not reflected in vital signs, although, in this small study, even elevated ETCO2 would miss 1 in 5 operative interventions (sensitivity 82%) and would incorrectly predict 1 operative intervention for every 4 correct predictions (specificity 82%).
If prospective study confirms that ETCO2 outperforms lactate levels as an indicator of hypoperfusion, perhaps it adds something to the trauma bay evaluation. Otherwise, it seems the most useful function might be to add to prehospital triage protocols – an environment where lactate wouldn’t be available.
“Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: A prospective cohort study”
http://www.ncbi.nlm.nih.gov/pubmed/23117381
More About ABIs Than You Ever Needed
These American Heart Association scientific statements are really quite lovely. Although much of the scientific discussion in this article pertains to the diagnosis of chronic vascular disease in the outpatient setting, measuring the ankle-brachial index has a place the the Emergency Department as well.
While most of the studies included in their mini-systematic review report AUCs for chronic peripheral vascular disease, the same principles apply for determination of acute peripheral vascular disease – relevant after lower-extremity penetrating trauma or fracture. And, if you’re going to use a test, sometimes it’s fun to know all the gritty details underpinning the evidence, how the cut-offs were determined, the difference between doppler and oscillometric devices, how discrepancies between legs should be handled, etc.
In any event, an interesting piece of literature to skim and save as a reference.
“Measurement and Interpretation of the Ankle-Brachial Index : A Scientific Statement From the American Heart Association”
Sometimes, The Pregnancy Test Lies
A couple years ago, my hospital pulled the POC urine pregnancy tests from the ED because of false negatives – leading to incredulous discussions of how it was possible for a nursing assistant to screw up something so simple as a dichotomous colormetric test.
Well, at Washington University, when they had multiple issues with their POC pregnancy test, they investigated the issue in more depth, and this nice little article is an overview of the limitations of the the test. There are two ways the POC test fails:
– Not pregnant enough.
– Too pregnant.
We all know about sensitivity in early pregnancy really only being 97% or so at one week, and no one will fault the test for that. However, their case series of five patients, all of whose serum hCG was >130,000, are hypothesized to have saturated the reagent to the point of a false-negative test.
In any event, interesting article about something I hadn’t put much thought into.
“‘Hook-Like Effect’ Causes False-Negative Point-Of-Care Urine Pregnancy Testing in Emergency Patients”
http://www.ncbi.nlm.nih.gov/pubmed/21835572
CT Coronary Angiography Screening Is Not Beneficial
Disclaimer: I despise CCTA for low-risk chest pain in the ED. It leads to additional unnecessary testing, interventions, and harms that outweigh the risk of coronary events in its target population. Our liability-sensitive practice has us evaluating an ever-increasing cohort of low- and (mostly) zero-risk young chest pain patients, and this is purported to be a test of choice for identifying a zero-zero risk population.
But there are just far too many false positives that have coronary artery disease of uncertain clinical significance.
This is a Korean study that compared 1000 matched controls that did not undergo CCTA with 1000 who did. 215 asymptomatic patients had positive CCTA – defined as any atherosclerotic plaque. 52 had >50% stenosis and 21 had >75% stenosis.
Their control cohort and their CCTA cohort were very similar – and 55-59% low risk, 34-29% intermediate, and 10% high risk based on NCEP risk stratification.
And their control group had a grand total of 1 cardiac event within their 18 month follow-up period, as did a single person in their positive CCTA group. However, the CCTA group ended up with more additional testing and cardiac revascularization procedures during their follow-up time frames – with no change in outcomes.
Now, these are asymptomatic patients chosen for screening – not the same as our chest pain patients in the ED – but it’s another call for caution regarding overtesting and overtreating.
Mandatory EKG Screening for Athletes
Discussion today in the public forum about this article:
Has been going around the internet. I only have access to the abstract, however, so I can only base my discussion on what data I see there. This is one of those articles that reviewed the rate of death in NCAA athletes for the last few years, and, essentially, they found that the incidence of sudden cardiac death was 2.28 event per 100,000 participant years. The commentary in the media: if only we had better screening!
Well, they tried that in Israel. Mandatory EKG screening was instituted in 1997 in an attempt to curtain SCD in athletes. The death rate before screening was 2.54 events per 100,000 participant years. Afterwards, 2.66 events per 100,000.
So, yes, if only we had better screening – because EKG alone doesn’t cut it. EKG + echocardiography? EP study? At some point, you have to take a rational look at the costs of something and realize it’s not taken out of an infinite pool of money – money that almost certainly could be put towards a much higher yield public health effort. Reactionary calls for more screening at this time are simply increased costs without proven benefit.