FFR(CT) – So Close, Yet So Far

As David Newman will tell you, the additive prognostic and predictive value for stress tests is fairly weak.  CT coronary angiograms are still a test looking for the correct population.  Conventional coronary angiography is expensive, invasive, and clearly not appropriate for the massive population of low risk patients we evaluate.

So, how about a non-invasive test that combines three-dimensional anatomic coronary reconstruction with predictive flow dynamics to identify lesions resulting in ischemia?  This test is CT coronary angiography combined with computed fractional flow reserve.  And, it would be a beautiful thing if it were ready for primetime – but it’s not.

I’ve reviewed a previous trial of FFR(CT).  This is a larger study, published in JAMA, of 285 patients with suspected CAD who underwent CCTA with FFR(CT), followed by conventional coronary angiography with invasive FFR measurement.  Figure 1 summarizes the results relatively succinctly – but essentially, 56 of the 172 FFR(CT) patients with lesions calculated as ischemic were false positives.  On the flip side, 67 of the 80 FFR(CT) patients with lesions calculated as non-ischemic were false negatives.  The per-vessel performance of FFR(CT) basically added no additional diagnostic AUC to CT alone.

The study is sponsed by HeartFlow, and authored by several physicians disclosing conflicts of interest with diagnostic imaging manufacturers.  Unsurprisingly, the authors try to spin the positive out of it in their conclusions and abstract.

Diagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography
http://jama.jamanetwork.com/article.aspx?articleid=1352969

Pop & Suture Abscesses Closed

Upending another slice of traditional dogma, brought to my attention by Andy Neill, this is a systematic review and meta-analysis of the 7 randomized clinical trials comparing primary closure of cutaneous abscesses with secondary.  I love articles that challenge routine practice – some of which was actually transcribed from stone tablets into Tintanelli by Moses.

Unfortunately, as weak as the evidence may be for packing abscesses, antibiotics with abscess, etc., the evidence from this meta-analysis really is only serviceable as underpinnings to justify further trials revisiting standard practice.  The 915 patients included in this meta-analysis were primarily anogenital abscesses drained in an operating room environment by surgeons and many received antibiotics.  Some of the outcomes measured in this study make sense and are probably generalizable – healing time and time off work – which obviously will favor the patients with primary closure.  The less generalizable is the 600 patient subset which tracked abscess recurrence, which also has a ton of heterogeneity between studies.

Is it reasonable to perform some sort of abscess closure?  I think it probably is – depending on the amount of potential disfigurement, there’s probably a discussion of risk/benefit that can be had.  There are also probably varying techniques of suturing that could be entertained, loosely approximating some part of the abscess, perhaps with a wick, rather than tightly re-approximating skin edges.


The authors state they are undertaking their own randomized trial.


“Primary closure of cutaneous abscesses: a systematic review”
www.ncbi.nlm.nih.gov/pubmed/20825801

Who’s Burned Out? We Are!

In a survey of U.S. physicians, published in Archives of Internal Medicine, Emergency Physicians hold the dubious honor of being the most “burned out” specialty.  This estimation of burnout is based on survey questions regarding emotional exhaustion, depersonalization, and personal accomplishment.  Unsurprisingly, dermatology was not a terribly burned out specialty – likely because they also ranked quite highly in time for personal and family life.  Surgical specialties, despite ranking at the bottom for family life, were only in the middle of the road for burnout – probably indicating the nature of the work plays a role in the strain.  Self-selection bias always plays a role in these surveys, of course, considering the response rate was only 26%.

Compared with the employed general population, physicians were more burned out and had less time for family – which may or may not be related to the 25% more hours per week worked, although, there were many differences between the physician cohort surveyed and the comparison.  

The New York Times discusses this article and uses a vignette of a “missed diagnosis” as symptomatic of the disruption of quality of care due to burnout.  While it may be true that burnout relates to healthcare quality, the specific case presented seems to fall more into a category of reasonable conservative management of the most likely condition, with appropriate further enquiry made at a re-visit due to persistent symptoms.

Burnout and Satisfaction With Work-Life Balance Among US Physicians Relative to the General US Population” 
http://archinte.jamanetwork.com/article.aspx?articleid=1351351

Head to Head With Head CT Rules

The “headline” you’ll see from this article is that the Canadian Head CT Rule outperforms the New Orleans Criteria for radiographic imaging in minor head trauma.  Specifically, it outperforms it in this prospective, observational cohort from several hospitals in Tunisia, consecutive patients with blunt trauma to the head and at least one symptom secondary to the head trauma.

The most striking thing about this article, however, remains the gruesome number of false positives generated by each of these head CT decision rules.  While, obviously, the intent is to capture all the cases requiring neurosurgical intervention, the New Orleans Criteria could not rule out potential need for neurosurgical intervention in 1,180 out of 1,582.  When the theoretical purpose of these rules is to prevent “scanning everyone”, we’re not getting much bang for our buck.  The Canadian Head CT Rule was better – but still indicated a need for scan in 656 out of 1,582.

While the article focuses mostly on the need for neurosurgical intervention in GCS 15 patients, it’s interesting to see their “secondary outcomes” which did not need “intervention”.  Only 34 total patients in their cohort required intervention – while they found 133 skull fractures, 41 subdurals, 45 epidurals, 69 subarachnoids/hemorrhagic contusions, and 1 case of pneumocephalus.  The Canadian rule would have missed 11 of the 218 “clinically significant” findings, for a sensitivity of 95%.  The article does not specific precisely which types of findings were missed, but, clearly, many of those may be argued to be not significant.  Unfortunately, deriving a better rule based on a more liberal definition of “clinical significance” is likely to result in more missed interventions – but it’s still probably worth trying.

“Prediction Value of the Canadian CT Head Rule and the New Orleans Criteria for Positive Head CT Scan and Acute Neurosurgical Procedures in Minor Head Trauma: A Multicenter External Validation Study”
http://www.ncbi.nlm.nih.gov/pubmed/22251188

How Fast Can We Rule-Out AMI?

Six hours?  Two hours?  One hour?  McDonalds’ drive-thru?

This is the paper from Archives of Internal Medicine that’s been making the rounds in the lay press regarding how quickly the ER should be able to detect your AMI with the new highly-sensitive troponins.  This is the APACE, prospective, international, multi-center study evaluating patients with “symptoms suggestive of acute myocardial infarction” and onset within the last 12 hours.

In this cohort, 1247 patients were recruited – and >300 were excluded for either going straight to the cath lab or having “another procedure performed” at the 1-hour time mark – and received hs-cTnT at index, 1, 2, 3, and 6 hours after presentation.  Myocardial necrosis was defined as a hs-cTnT >99th percentile, which for this assay is 14 ng/L, and a diagnosis of acute MI was made by two independent cardiologists upon review of records and lab results.

The authors split their cohort into two groups, a derivation cohort and a validation cohort, and did some statistical wrangling to come up with two cut-off strategies – one for rule-in and one for rule-out.  They were able to make diagnostic decisions on ~76% of their cohort at the one-hour time point, and 52 ng/L at presentation or an increase within an hour of 5 ng/L or more was ~94% specific for AMI.  Likewise, 12 ng/L and an increase less than 3 ng/L at 1 hour was ~100% sensitive for AMI.  The remaining 25% of their cohort was in a non-diagnostic zone.  At 30 days, there was one death in their rule-out cohort, for a 99.8% survival rate.

So, can you use this strategy?  If you feel as though this study is externally valid to your populations and you’re using the same Roche Diagnostics test, you certainly may.  Every piece of data is something you can incorporate to your discussions with a patient regarding diagnostic certainty and risk.  Even an extra hour occupying an ED bed rather than moving out to a chest pain observation facility can significantly impede ED flow, while observation admissions are costly and inconvenient to patients.  The ideal strategy will depend on the capabilities of individual departments.

This study, along with the primary author, are sponsored in part by Abbott, Roche, and Siemens.
www.ncbi.nlm.nih.gov/pubmed/22892889

Intensive Blood Pressure Control in ICH

Not much works to treat ICH – and this retrospective analysis of INTERACT1 tries to coordinate a couple leaps to pull a different spin out of old data.  Unfortunately, it’s still a re-analysis of essentially a negative trial, and that limits its utility for the purists.

INTERACT1 randomized patients with ICH to either “intensive” blood pressure lowering or conventional treatment – most of whom received some BP control – and noted significant improvements in hematoma volume.  However, the 90-day safety/clinical outcomes data did not show any difference in mortality or dependency.  This publication reverses the strategy, taking a look at the associations between good clinical outcomes and hematoma volume – and finds that increases in hematoma volume at 24 hours clearly predict poor clinical outcomes.

So, if intensive BP control reduces hematoma expansion and reduced hematoma expansion improves clinical outcomes, then why was INTERACT1 negative?  I suspect we’ll find out more when INTERACT2 is published….

“Hematoma growth and outcomes in intracerebral hemorrhage: The INTERACT1 study”

“Propoven”

Medication shortages are affecting many hospitals – we’re low/out of prochlorperazine, injectable metaclopromide, etomidate, propofol, brevital – and one of the replacements we’ve recently been introduced to is “Propoven”, a European manufacture of propofol.

It has only minor differences from propofol, but it should be noted it requires strict sterile technique when handling and has more medium-chain fatty acids.  An informational letter from Kabi describing a few of the differences is here:

AHRQ Infection Control @ ACEP

Jeremiah Schuur, featured on EM Lit of Note for his timely critique of the inadequacy of the “quality” measure for non-contrast head CT, passes along a notification of a pre-ACEP conference in ED infection control practices.


Sponsored by AHRQ, ACEP, and infection control societies, find more information about the conference here:

http://edip.partners.org/conference/

Honey For Pediatric Cough

Sponsored by the Honey Board of Israel, this small study supposes to demonstrate that honey is superior to control in the treatment of pediatric nighttime cough.  Specifically, honey is superior to silan date extract, which apparently resembles and tastes like honey.


This is a prospective, double-blind study of three different honey arms and one control arm.  Each group had approximately the same pre-intervention symptomatology severity – cough severity, bothersome nature of the cough, and sleeplessness for bother parent and child – and all interventions improved symptoms.  The scores, supposing clinical relevance to a 0.75 difference in score on a 4-point scale, were significantly improved by all interventions.  Then, the various types of honey all either strongly trended towards or reached statistical superiority over the silan date extract.


So, if your child has a cough – honey seems to be a reasonable intervention.  If you don’t have honey, give them silan date extract!  If you have neither – well, just don’t use dextromethorphan.  And, 20% of infant botulism cases are traced to contaminated honey, so the current recommendation is not to give honey to patients aged less than 1 year.


Incidental note is also made by the authors that some children likely disliked the more aromatic eucalyptus and citrus honeys.


“Effect of Honey on Noctural Cough and Sleep Quality:  A Double-blind, Randomized, Placebo-Controlled Study”
http://www.ncbi.nlm.nih.gov/pubmed/22869830

Platelet Transfusion & Intracerebral Hemorrhage


This systematic review is published in Annals of Emergency Medicine under the section heading of “Best Available Evidence”, which somehow to me seems to pleasantly understate the unfortunate lack of data on this topic.


Intracererbral hemorrhage in the setting of antiplatelet use unfortunately is one of those clinical situations where outcomes are so dire that the philosophy seems to be to throw the kitchen sink of potentially beneficial interventions at patients.  Use of clopidogrel, and to a lesser extent aspirin, are associated with increased hematoma size and poorer outcomes.  Platelet transfusions, using measures of platelet aggregation activity, are demonstrated to improve and reverse inhibition in approximately two-thirds of patients.  Therefore, it follows that platelet transfusions would improve outcomes in intracranial hemorrhage.


Unfortunately, the “best” evidence – which is mostly retrospective data of small cohorts – fails to demonstrate any improvement in mortality or morbidity.  It is not possible to say from the data whether the platelets do not show efficacy at treating the extension of the ICH, or whether the poor outcomes result from parallel transfusion-related complications.  The article concludes that withholding platelet transfusion should be considered to be within the standard of care.  I tend to agree that resource-intensive treatments should be required to demonstrate benefit before widespread adoption, and therefore agree with these authors.


The authors additionally note a prospective, multicenter trial is underway.


“Does Platelet Transfusion Improve Outcomes in Patients With Spontaneous or Traumatic Intracerebral Hemorrhage?”

http://www.ncbi.nlm.nih.gov/pubmed/22841709