Author: Ryan Radecki

Ultrasound First For Pulmonary Embolism?

Akin to the ultrasound first for appendicitis protocol currently in use, the authors of a recently published study in CHEST propose using ultrasound before CTPA in patients where the diagnosis of pulmonary embolism is being considered.

Their protocol consisted of bedside thoracic and lower extremity ultrasounds to identify either a confirmatory DVT or an alternative diagnosis that would account for the patient’s current presentation. In both the ED and inpatient settings,  ICU physicians evaluated this protocol’s performance in 100 patients. The 54 patients who were determined, due to an alternative diagnosis found on ultrasound, not to require further testing, none of them were found to have a pulmonary embolism on confirmatory CT. Of the remaining 40 patients (42%) whose ultrasound revealed no convincing alternative diagnosis or lower extremity DVTs, 12 were found to have pulmonary embolisms on their confirmatory CTPA. The authors conclude that though further studies are needed, an ultrasound first strategy will reduce the number of CTs obtained to rule out pulmonary embolism.

Though I am not opposed to the utilization of ultrasound as a bedside tool, using it to rule out pulmonary embolisms is a flawed paradigm. The proposed protocol is not one which rules out PE, it in fact does just the opposite. This protocol takes advantage of the high specificity of ultrasound for the diagnosis of pneumonia, pulmonary edema, and DVT. It employs the strategy of ruling in an alternative diagnosis or a lower extremity DVT. If no convincing diagnosis is discovered the patient will then move on to the more traditional rule out strategy of CTPA. This study essentially uses bedside ultrasound to address the  two most heavily weighted criteria on the Well’s Score, “an alternative diagnosis that is less likely than pulmonary embolism” and  “signs and symptoms of deep venous thrombosis”. In no way is this protocol fatally flawed. It has the potential to add a great deal to clinical decision making. Unfortunately it does not address the more serious epidemic in the current management of pulmonary embolisms. That is the egregious over-testing and subsequent over-diagnosis of pulmonary embolism in the ultra low risk patient.

“Ultrasound Assessment of Pulmonary Embolism in Patients Receiving Computerized Tomography Pulmonary Angiography”
journal.publications.chestnet.org/article.aspx?articleid=1763837

For more nihilism, emergency medicine and the art of doing nothing see emnerd.com and @CaptainBasilEM

Ultrasound First For Pulmonary Embolism?

Akin to the ultrasound first for appendicitis protocol currently in use, the authors of a recently published study in CHEST propose using ultrasound before CTPA in patients where the diagnosis of pulmonary embolism is being considered.

Their protocol consisted of bedside thoracic and lower extremity ultrasounds to identify either a confirmatory DVT or an alternative diagnosis that would account for the patient’s current presentation. In both the ED and inpatient settings,  ICU physicians evaluated this protocol’s performance in 100 patients. The 54 patients who were determined, due to an alternative diagnosis found on ultrasound, not to require further testing, none of them were found to have a pulmonary embolism on confirmatory CT. Of the remaining 40 patients (42%) whose ultrasound revealed no convincing alternative diagnosis or lower extremity DVTs, 12 were found to have pulmonary embolisms on their confirmatory CTPA. The authors conclude that though further studies are needed, an ultrasound first strategy will reduce the number of CTs obtained to rule out pulmonary embolism.

Though I am not opposed to the utilization of ultrasound as a bedside tool, using it to rule out pulmonary embolisms is a flawed paradigm. The proposed protocol is not one which rules out PE, it in fact does just the opposite. This protocol takes advantage of the high specificity of ultrasound for the diagnosis of pneumonia, pulmonary edema, and DVT. It employs the strategy of ruling in an alternative diagnosis or a lower extremity DVT. If no convincing diagnosis is discovered the patient will then move on to the more traditional rule out strategy of CTPA. This study essentially uses bedside ultrasound to address the  two most heavily weighted criteria on the Well’s Score, “an alternative diagnosis that is less likely than pulmonary embolism” and  “signs and symptoms of deep venous thrombosis”. In no way is this protocol fatally flawed. It has the potential to add a great deal to clinical decision making. Unfortunately it does not address the more serious epidemic in the current management of pulmonary embolisms. That is the egregious over-testing and subsequent over-diagnosis of pulmonary embolism in the ultra low risk patient.

“Ultrasound Assessment of Pulmonary Embolism in Patients Receiving Computerized Tomography Pulmonary Angiography”
journal.publications.chestnet.org/article.aspx?articleid=1763837

For more nihilism, emergency medicine and the art of doing nothing see emnerd.com and @CaptainBasilEM

hsTnI – All Promise, No Proof

At some point, it is true – there are no “bad” tests, only “bad” applications and interpretations of those tests.  One of those tests, as supported by Abbott Laboratories, is the high-sensitivity troponin.  You may also know this test as the “low-specificity” troponin – as, barring small improvements in the assay, a more sensitive test for the same biomarker is bound to result in decreased specificity.

This article describes the populations of ADAPT and APACE for whom high-sensitivity troponins are available.  These trials were part of a prospective derivation of an “accelerated diagnostic protocol,” in which low-risk patients (TIMI 0 or 1) with normal ECGs and two negative hsTnI two hours apart were found to be eligible for discharge from the Emergency Department.  With an approximately 14% of 30-day MACE (mostly nSTEMI) in each cohort, the authors strategy is reasonable:  only ~0.7% of patients meeting these three criteria eventually met a primary endpoint.

Conversation about this article led to this tweet by the primary author:

@EMManchester @240minDoc Precision of hs #troponin assays now shown to have great advantage. ED patients with possible ACS and this assay 1
— Louise Cullen (@louiseacullen) November 7, 2013

… except it isn’t entirely true.  The missing key to this statement is precisely what the “great advantage” entails.  These authors, sponsored by Abbott Laboratories, do not show this diagnostic strategy utilizing hsTnI is in fact superior to the same strategy using conventional troponins.  Quick back-of-napkin math shows the ADAPT conventional troponin cohort using this same strategy gives statistically similar results.  This critique led to the final tweet from the primary author:

@emlitofnote @EMManchester @240minDoc OK have to wait til part II where I can show you larger pop and more narrow CIs.
— Louise Cullen (@louiseacullen) November 8, 2013

Yes, with sufficient statistical power, there will likely be a reproducible difference between the different troponin assays.  When millions of patients are evaluated for chest pain every year, there may be a few for whom this improved sensitivity is clinically significant.  However, it is far more likely this increased sensitivity will end up referring additional patients for testing – resulting in increased costs and harms from overdiagnosis.  This is not the fault of the test – but, rather, simply that we don’t yet know the clinical significance of all small troponin elevations, and there is no appropriate algorithm for managing them in current practice.

I actually like what these authors are doing – using a rapid rule-out plus risk-stratification to safely discharge patients from the Emergency Department.  However, they’re selling hsTnI without proving it’s superior, in this strategy, to conventional troponin testing.  Then, as tests become more sophisticated, our interpretation of them needs to as well – and studies such as these need to do more than simply describe a “minimal-risk” cohort, but also provide useful guidance on the rest of the grey area troponin elevations.

Finally, I’d also like to finally see the TIMI score retired for use in the Emergency Department.  Please. Make it die.

“Validation of High-Sensitivity Troponin I in a 2-Hour Diagnostic Strategy to Assess 30-Day Outcomes in Emergency Department Patients With Possible Acute Coronary Syndrome”

Letter in JAMA

A couple months back, JAMA published Jeff Saver’s time-to-tPA association, derived from the Get With the Guidelines-Stroke Registry.  My critique of this article remains essentially the same, but this past issue JAMA published an edited version as a response to Dr. Saver.

While many of you will find the content behind the JAMA paywall, the basic gist of Saver’s response to my letter is:

  • tPA-treated stroke mimics are not included in the GWTG-Stroke registry during the study period.  It is an optional reporting field.
  • The tiny bit of data from original NINDS showed rapidly-improving patients from the placebo group were equally distributed between 59 to 90 minutes and 91 to 180 minutes (3/145 vs. 4/167).
  • The onset-to-treatment-time and outcome association was consistent between NIHSS 0-14 and NIHSS 15-42, and therefore any effects from TIAs must be insignificant.

In summary: they don’t really know how many TIAs/stroke mimics/aborted strokes there were, but they can draw lines around some numbers to support their conclusion.

These are reasonable responses from their standpoint.  I would point out, however, the NINDS group made specific efforts to exclude “rapidly improving” symptoms from inclusion, probably resulting in extreme extra care in preventing enrollment of TIAs.  This population is unlikely to be generalizable to current tPA-happy practice across medicine.  They do not, unfortunately, address the problem of “aborted stroke” coding, which further received a shout-out on Twitter from Dr. Hsia:

@emlitofnote hit the mark in @JAMA_current with citing our averted #stroke paper: #tPA-treated does not equal #stroke http://t.co/6aE7bFlm7k
— Amie Hsia (@DCStrokeDoc) November 8, 2013

I’ll try and get a peek at the GWTG-Stroke data myself, but with the literature documenting anywhere from 2% to 31% stroke mimic treatment rate – with the actual true rate probably exactly in the middle of that range – it’s critically important to uncover risks and costs of inappropriate tPA administration.  If the GWTG-Stroke registry is a true quality device, it needs to do a better job of measuring adverse events.

Or, you could end up like Houston Texans’ coach Gary Kubiak, who received tPA last week for a stroke mimic (currently reported as having had a TIA – which I find dubious, but I have no personal knowledge of the case).

“Acute Ischemic Stroke and Timing of Treatment”
http://www.ncbi.nlm.nih.gov/pubmed/24193085

Strep Throat? Stay Home!

NBC News covered this useful-seeming innovation last week – a predictive score to help patients decide whether their sore throat might be caused by Group A Strep.  It seems a quite reasonable proposition on the surface – if patients can receive guidance on their pretest likelihood of disease, they might rather not seek unnecessary medical care.  For the 12 million physician visits every year for sore throat, putting a dent in this would account for sizable cost savings.

This study describes retrospective development of a “Home Score” for use by patients, based on a MinuteClinic database of 71,000 sore throat presentations for which a strep swab was performed.  The authors split the data into a derivation and a validation set, and produced a complex mathematic scoring system, from 1 to 100, based off age, fever, cough, and biosurveillance data.  Using a score of 10 as a cut-off, the validation set sensitivity was 99%, specificity was 1%, and the prevalence data used resulted in a validation negative predictive value of 87%.  This NPV, the authors say, is the important number regarding advising patients whether they ought to seek care for GAS.

There are a few issues with this derivation, of course.  First of all, the derivation population is subject to selection bias – as only patients with strep swabs are included.  Then, the MinuteClinic data has to be generalizable to the remaining adult population.  The use of the Home Score also depends on the availability of biosurveillance data for their specialized algorithm.  Finally, their NPV cut-off of 90% would theoretically obviate clinic visits for only 230,000 of the 12 million patients seeking care for sore throat – a large drop, but only a drop in the bucket, nonetheless.

And, the elephant in the room: Group A Strep doesn’t need antibiotics in the United States.  The likelihood of adverse reactions to treatment of GAS exceeds the chance of benefit – whether progression to peritonsilar abscess or rheumatic fever is considered.  A few folks on Twitter chimed in to echo this sentiment when this story was discussed:

@embasic @DrLeanaWen @MDaware @NBCNewsHealth just need to redesign app to say “no you don’t” regardless of sx
— Anand Swaminathan (@EMSwami) November 10, 2013

There are legitimate reasons to visit a physician for sore throat – but, in the U.S., nearly all uncomplicated pharyngitis can safely stay home, GAS or not.

“Participatory Medicine: A Home Score for Streptococcal Pharyngitis Enabled by Real-Time Biosurveillance”
http://www.ncbi.nlm.nih.gov/pubmed/24189592

Another Appeal for Prudent Antibiotics

Bronchitis, deadly scourge of man – at least, considering the quantity of antibiotics prescribed, it must be, right?

Or, the cure is worse than the disease, as these authors seem to demonstrate.  This is a parallel, single-blinded, placebo-controlled trial in 9 primary care centers in Catalonia, Spain, enrolling patients with acute bronchitis.  Non-immunosuppressed patients with a productive cough of less than a week’s duration were randomized to amoxicillin-clavulanic acid, ibuprofen, or placebo for a 10 day course.  The primary outcome was time to cure, with treatment failure and safety outcomes as secondary outcomes.

With approximately 140 patients in each group, the only clinically meaningful significant difference between groups was the incidence of adverse events in the amoxicillin-clavulanic acid group.  These were mostly gastrointestinal events, occurring in 12% of the antibiotic group, compared with 5% of the ibuprofen group and 3% of the placebo group.  Days with cough, treatment failure, and time to overall symptom resolution showed no significant differences between groups.  There was some suggestion of a trend towards benefit from the ibuprofen arm, but this would have to be confirmed in a larger trial.

The main limitation of this article is failure to include a macrolide antibiotic as a comparator, considering the expected bacterial epidemiology of ambulatory respiratory infections.  Regardless, this adds to the body of evidence demonstrating the futility of antibiotics in healthy patients with bronchitis – and I’d expect similar findings even if azithromycin were included.

“Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial”
www.ncbi.nlm.nih.gov/pubmed/24097128

Bivalrudin Trumps Heparin (Or Not)(Who Knows?)

10 out of 10 physicians employed by the Medicines Company approved this message.

Straight out of Jeff Drazen’s unbiased news pipeline, a treatment you might now start seeing more of in the Emergency Department: bivalrudin (Angiomax) for anticoagulation prior to PCI in the setting of STEMI.  In this trial, 2,231 patients across Europe were randomized pre-hospital (or at non-PCI hospitals) to either bivalrudin or heparin plus optional glycoprotein IIb/IIIa inhibitor.  The primary outcome, as typical of these sorts of trials, is another muddled composite: death from any cause, re-infarction (MI), or major bleeding not related to CABG.

Oh, wait, that was the original primary outcome.  In December of 2012, over three-quarters of the way through the enrollment period, the Medicines Company dropped re-infarction (MI) from the primary outcome.  It may or may not be a coincidence re-infarction due to stent thrombosis favored the control intervention, but I will leave that speculation up to the astute reader.  Regardless, the new final composite endpoint favored bivalrudin: 5.1% to 8.5%.  However, this outcome also depends on their own unique definition of “major bleeding”, which is different from TIMI and GUSTO.  If the TIMI and GUSTO definitions are used, the trend towards reduced bleeding with bivalrudin is still there, but the absolute differences become trivial and the overall primary outcome (original or eventual) is a wash.  Finally, this may all simply be a straw-man comparison for the safety outcome, as it’s reasonable to ask whether 69% of cases ought to be receiving prehospital glycoprotein IIb/IIIa inhibitor (an AHA Class IIb recommendation).

However, better questions may be – as are a recurring theme for the NEJM – do you trust the results of an open-label trial sponsored by the manufacturer, designed by the manufacturer, with data stored and dispensed to the academic oversight group by the manufacturer?  Are you less or more convinced when four authors are employed by the manufacturer, and the manufacturer employed a scientific communications firm for “editorial support”?  Why is NEJM publishing a trial that changed its primary outcome in clinicaltrials.gov – even, as the authors claim, to “reduce the necessary sample size”?

Physicians ought to be outraged at this transparent and unbalanced pharma shill – but, such occurrences have become so commonplace, it’s hard to not just surrender to lassitude.  Bivalrudin doubtless has an advantage in some specific subgroup, but with this sort of offal clogging the evidence, we’ll never really know.

“Bivalirudin Started during Emergency Transport for Primary PCI”
www.ncbi.nlm.nih.gov/pubmed/24171490

Unicycles, Not All Fun And Games?

Finally a study on Unicycles! According to Dr. Marvin Wang, the author of the recently published article “Unicycle Injuries In the United States”, his chart review of the National Electronic Injury Surveillance System (NEISS) is the entirety of the world’s literature on unicycle injuries. To my utter disappointment there were zero cases of falls from a tight rope or burns from a mishandled flaming juggling pin. Even the author himself observes that unicycles, once exclusively ridden by professional “circus folk” and acrobats, have now become primarily an amateur endeavor.
Ironically the same inherent mechanics and “sense of danger” that made the unicycle a popular circus act, makes it far safer than its two-wheeled cousin when used by the general public. Because of its single wheel, riders are far less capable of attaining high speeds and it is therefore infrequently used as a functional means of transportation. Given this lack of functional utility, riders of unicycles seem to have escaped the more serious types of cycle accidents such as high-speed crashes and collisions with motor vehicles. Upon review of the 85 cases of documented unicycle injuries found in the NEISS database from 1991 to 2010, the author extrapolates that 168 people a year visit the emergency department for unicycle related injuries in the United States. The most common injuries acquired were extremity fractures, sprains and strains. Very few head and neck injuries occurred, and the majority of these were scraps and abrasions.
The biggest weakness of this study is that we are unable to determine a denominator. Since we do not know what percentage of the US population at any time are riding unicycles, we are unable to quantify the risk of riding such a contraption. It may be that only a small percentage of riders will sustain an injury that requires an ED visit. Conversely it is possible that the risk is much higher. If you do decide to mount one of these single wheeled cycles you may be taking your life, or at least your limb into your own hands…
“Unicycle Injuries In the United States”
www.ncbi.nlm.nih.gov/pubmed/23871477
For more nihilism, emergency medicine and the art of doing nothing see emnerd.com and @CaptainBasilEM

Unicycles, Not All Fun And Games?

Finally a study on Unicycles! According to Dr. Marvin Wang, the author of the recently published article “Unicycle Injuries In the United States”, his chart review of the National Electronic Injury Surveillance System (NEISS) is the entirety of the world’s literature on unicycle injuries. To my utter disappointment there were zero cases of falls from a tight rope or burns from a mishandled flaming juggling pin. Even the author himself observes that unicycles, once exclusively ridden by professional “circus folk” and acrobats, have now become primarily an amateur endeavor.
Ironically the same inherent mechanics and “sense of danger” that made the unicycle a popular circus act, makes it far safer than its two-wheeled cousin when used by the general public. Because of its single wheel, riders are far less capable of attaining high speeds and it is therefore infrequently used as a functional means of transportation. Given this lack of functional utility, riders of unicycles seem to have escaped the more serious types of cycle accidents such as high-speed crashes and collisions with motor vehicles. Upon review of the 85 cases of documented unicycle injuries found in the NEISS database from 1991 to 2010, the author extrapolates that 168 people a year visit the emergency department for unicycle related injuries in the United States. The most common injuries acquired were extremity fractures, sprains and strains. Very few head and neck injuries occurred, and the majority of these were scraps and abrasions.
The biggest weakness of this study is that we are unable to determine a denominator. Since we do not know what percentage of the US population at any time are riding unicycles, we are unable to quantify the risk of riding such a contraption. It may be that only a small percentage of riders will sustain an injury that requires an ED visit. Conversely it is possible that the risk is much higher. If you do decide to mount one of these single wheeled cycles you may be taking your life, or at least your limb into your own hands…
“Unicycle Injuries In the United States”
www.ncbi.nlm.nih.gov/pubmed/23871477
For more nihilism, emergency medicine and the art of doing nothing see emnerd.com and @CaptainBasilEM

The Trauma Log Roll is Dead

Among unproven interventions, back-boarding, cervical collars, and log-rolling have been part of the dogma of trauma since Alfred Nobel invented the electric slide.  We’ve finally started to put an end to uncomfortable and unwarranted back-boarding, we’ve re-designed cervical collars, and this article takes on log-rolling.  The assertion of these authors is clinical examination of an otherwise alert major trauma patient is unreliable, does not obviate imaging, and may thereby be omitted from the initial secondary survey.

Unfortunately, this is a very specific, limited, retrospective registry review.  Only patients from the trauma registry at the Alfred Hospital were included: major trauma (ISS >15) and admitted for 24 hours, or isolated thoracolumbar injuries requiring 72 hours of hospitalization.  This identified 1,161 patients with thoracolumbar fractures, and these authors further pared it down to 538 who were GCS >15 as their proxy for potentially reliable examination.  How many of these alert, appropriate trauma patients with thoracolumbar fractures complained of pain on log-roll and spinal palpation?

60.3%.

So, yes, if the clinical examination is only 60.3% sensitive for significant thoracolumbar fractures, then we ought to stop bothering to log-roll our patients.  But, generalizing the evidence from this retrospective review in a highly selected population is grossly irresponsible.  It is reasonable, as the accompanying letter states, if the decision has already been made in a major trauma to progress to full-body computed tomography – a test more sensitive and specific for spinal fractures than clinical examination – log-roll and complete physical examination may be deferred.  The theoretical risks to log-roll – lack of true thoracolumbar stability, possibility of disturbing internal hemostasis – if there is no benefit, are appropriate considerations if physical examination does not change clinical evaluation.  It is, however, excessive to universally posit, as the letter authors do, “Log-rolling a blunt major trauma patient is inappropriate in the primary survey.”

“Can initial clinical assessment exclude thoracolumbar vertebral injury?”
www.ncbi.nlm.nih.gov/pubmed/22915226‎

“Log-rolling a blunt major trauma patient is inappropriate in the primary survey”
www.ncbi.nlm.nih.gov/pubmed/24136122‎