Ceftaroline – The New Wonder Drug

Don’t use it.

If you’re like me, every journal you pick up nowadays has a three page glossy fold-out of some confident-looking fake doctor showing off the new broad-spectrum magic medicine, ceftaroline fosamil (Teflaro).  600mg IV q12, ask your doctor if you should be receiving Teflaro.

So, finally, when I got a booklet mailed to my house, I gave in and looked at the literature.  And, I was almost legitimately defeated by the literature because most of the recent, relevant published literature regarding outcomes in the phase III trials…is written by employees of Forest Laboratories and published in a special “clinical supplement” to an infectious disease journal.  There isn’t much data out there that isn’t just advertising.

However, my survey of the animal studies, and presuming the human studies aren’t blatantly made up, seems to indicate this is a great antibiotic.  It doesn’t work against VRE, pseudomonas, ESBL e. coli, ESBL klebsiella, or acinetobacter, but it’s active against many strains of MRSA, DNS MRSA, and VISA, along with the other strep and staph we worry about.

Which is exactly why we shouldn’t use this antibiotic – it’s so good it should be on every hospital’s formulary, but locked in a vault with the same key system a nuclear launch requires.  Keep it as third- or fourth-line to prevent additional resistances.  But, don’t use it.

Sadly, the article I have for you is just a review of all the manufacturer-supported data – but at least it’s not written by them.

“Ceftaroline: a comprehensive update.”
http://www.ncbi.nlm.nih.gov/pubmed/21420284

Patients Bleed When On Aspirin and Plavix

And they bleed a heck of a lot more on Plavix than Aspirin.  This is probably the first article I’ve ever read out of Academic Dermatology, and it’s mildly relevant to EM in the sense that we perform a lot of minor cutaneous procedures – suturing, I&D, etc.

This is a retrospective review of bleeding associated with minor surgical dermatology, and, the good news, it was rare – at 0.3% of cases on clopidogrel, and even rarer on aspirin alone, and then zero when on neither.  Bleeding doesn’t stress us out as much, probably, so this isn’t practice changing.  They do importantly mention in their discussion that holding/changing these medications prior to the procedure can be associated with thrombotic complications – I wouldn’t be rushing off to give DDAVP to wake any platelets up if I ran into procedural troubles.

“Complications of cutaneous surgery in patients taking clopidogrel-containing anticoagulation.”
http://www.ncbi.nlm.nih.gov/pubmed/21514003

Public Insurance Places Children At Risk

Determining proper payment for healthcare services is a fascinating problem of substantial complexity, and, with the “Affordable Care Act” and various past and future movements towards public insurance, there is a great deal of uncertainty regarding physician payment – both in the amount (public vs. private insurance) or whether (uncompensated care in hospitals, emergency departments).

This is a very interesting study out of NEJM that is applicable to the 70 to 80% of emergency departments we send home with instructions to “follow-up with X”.  They nicely demonstrate that, in Chicago, at least, “follow-up with X” is nearly trivially easy with private insurance, and much more difficult if funded by one of their Medicaid providers for children.  Excepting child psychiatry – which is in shortage – when calling a specialist for follow-up claiming to have private insurance, their research assistants could schedule an appointment well over 90% of the time.  Alternatively, when stating they had public insurance for their child, ability to follow-up ranged from 20 to 57%, depending on the specialty.

Not only that, public insurance patients waited a mean of 42 days for their appointment versus 22 days for private insurance, when they looked at clinics that would even accept that insurance option.

And, the clinical scenarios they presented for follow-up were not just routine new patient appointments – they were pediatric patients with legitimate uncontrolled morbid disease with the potential to significantly worsen and impact their overall health.

I don’t have a solution to a complex social, financial, and political problem with complex social, financial, and political obstacles – but the more good articles like this are published, the more likely smart folks will start working on solutions.

“Auditing access to specialty care for children with public insurance.”
http://www.ncbi.nlm.nih.gov/pubmed/21675891

Do Not Use Etomidate/Fentanyl For Orthopedic Reduction In Children

Sometimes, when I read a study, I think to myself – great study!  If only they had sufficient enrollment to have power and validity!  When I read this study, I thought, Heavens to Betsy – I am so glad they only subjected 12 patients to etomidate/fentanyl for sedation.

This is comparing ketamine/midazolam to etomidate/fentanyl for procedural sedation and the authors hoped that, perhaps, the shorter duration of action of etomidate would make it a viable alternative.  But, it isn’t.  Objective measures of procedural distress favored ketamine, parents favored ketamine, and the practitioners favored ketamine.  Sedation time and recovery time favored etomidate – but at what cost?  18% of the ketamine group had an adverse event (vomiting, emergency reaction), while 50% of the etomidate group did (hypoxemia, etc.)

Propofol/fentanyl may be considered, but not etomidate/fentanyl.

“Ketamine/midazolam versus etomidate/fentanyl procedural sedation for pediatric orthopedic reductions.”
http://www.ncbi.nlm.nih.gov/pubmed/20502386

Sensitivity of CT Angiography for Aneurysms

Not exactly the article I was expecting when I pulled it, but mildly interesting nonetheless.  The real applicability of this article is towards those folks who say the LP for SAH is outdated, and we should just proceed with CTA to identify the culprit aneurysm.

As opponents say, many aneurysms identified by CTA are asymptomatic and unrelated to the acute headache in the Emergency Department, and, without the LP, you don’t know their clinical relevance.  This study lets them also say that CTA doesn’t even necessarily perform well enough at this task to warrant use – it will miss 5% of aneurysms and overcall 3.8%.

However, it must be said, this meta-analysis uses data from a number of old studies that have older CT scanners that were very poor at detecting <4mm aneurysms.  Once you get to 16 and 64 row CT, your sensitivity is closer to 98-99% – and then you have to fall back to the asymptomatic/clinical relevance argument.

“Diagnosing cerebral aneurysms by computed tomographic angiography: meta-analysis”
http://www.ncbi.nlm.nih.gov/pubmed/21391230

Neurothrombectomy Devices – Still Not The Answer

Catheter-based endovascular treatment of acute ischemic stroke has been around for several years – this is a nice, concise review of the published literature regarding their use.

The abstract sounds a little more favorably skewed than the actual content of the article – their discussion is appropriately skeptical regarding the efficacy and applicability of this particular treatment modality.  It is certainly true that restoring flow to affected regions in stroke is advantageous, and the theory behind the use of these devices is to mechanically ensure open vessels in situations where systemic thrombolysis may not be efficacious and the disability is likely to be profound.

The problem is, there really isn’t any “evidence” in this article.  The published literature on this topic is primarily retrospective cohort/case-reports by industry-affiliated inventors of these devices and, even despite this bias, that literature tends to report unacceptable levels of procedural complications while trying desperately to show benefit.

Regardless, as the authors mention, there are many studies of MERCI and Penumbra ongoing – slowly chasing that inexorable statistical probability of finally performing enough studies that, by chance, one of them will be favorable enough upon which to base widespread marketing efforts.

“Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence”
http://www.ncbi.nlm.nih.gov/pubmed/21242342

Patients With Brugada May Have Normal EKGs …and Then Drop Dead

The sodium-channelopathy that went many years before being described, now increasingly well-known.  More interestingly, the phenotype is apparently autosomal dominant in inheritance.  These investigators use this inheritance to retroactively diagnose deceased family members with a Brugada cause to their sudden cardiac death.

They found, unfortunately, that not only were most individuals who died of Brugada young, most were asymptomatic – and of the five patients for whom they could find an antemortem EKG, only one of them had a typical Type I Brugada pattern, and one had a single lead with a Type III pattern.

I think my take-home point from this article is that, in the young patients presenting with syncope, it’s important not just to do the EKG, but also to enquire regarding family history of sudden cardiac death – and then hope whatever cardiologist you refer them to is insightful enough to order a amajaline provocation test if needed.

http://www.ncbi.nlm.nih.gov/pubmed/21636035

Significant Populations Have No Timely Access to Stroke, Pediatric Trauma Care

These are a couple studies from a family of publications that use population data, GIS mapping tools, and travel times by air and ground to estimate what percentage of the population has access to a certain healthcare resource.  In these two papers, the resources in question are Primary Stroke Centers and Pediatric Trauma Centers.  They estimate that 71% of the pediatric population is within 60 minutes of a pediatric trauma center by ground or air – which is appropriate, because trauma systems are set up to use aeromedical transport.  However – and, depending on what direction the TPA pendulum swings – only 55.4% of the population has access to a stroke center within 60 minutes – by ground, which is typical.  They say this could be increased to 79% within 60 minutes if aeromedical resources were involved, but I think we should wait to establish a greater treatment effect for acute stroke treatment before we go nuts with air travel.

I like maps; I worked with one of the authors (Dr. Branas) on previous iterations of descriptive articles similar to these.  The problem with these articles is the statistic they describe – timeliness of care – may or may not have significant effects on patient outcomes.  And, in theory, the solutions – moving trauma center designations, establishing new stroke centers, increasing aeromedical use, etc., have significant costs and unintended consequences.

http://www.ncbi.nlm.nih.gov/pubmed/20937948
http://www.ncbi.nlm.nih.gov/pubmed/19487606

Shoulder Reduction – Spanish-Style

Another interesting article regarding shoulder reduction techniques.

Essentially, what I read into shoulder reduction is that – if there many usually successful ways to do something, pretty much anything works.  And, what seems to be the generally accepted way to do it – excepting the scapular manipulation technique – is pulling on it.  What is different between methods seems to be how exactly you apply the traction.

This is a single-operator method with direct axial traction on the distal humerus with one hand and counter-traction on the acromium with the other hand.  The trouble I foresee with this method is that you’re fighting a lot of large muscles on the patient with your own, smaller, rotator cuff and shoulder abductors.  I think you’d end up fatiguing before a lot of your patients.

The variation I might suggest is the snowbird technique, where you use the weight of your leg to provide downward traction via stockinette around the forearm.  You can sometimes get away from having to do full procedural sedation if you can perform a technique like this where the patient fatigues before you do.

http://www.ncbi.nlm.nih.gov/pubmed/21620607

rFactor VII Is Not Safe (Despite Their Conclusions)

When NovoNordisk writes an article analyzing safety data from the CONTROL trial, you get a skewed perspective on the data.  Specifically, if you only read the abstract, you’re going to think that it’s safer in some ways(ARDS was less), and there was no difference in adverse events (except for all that investigator-reported AMI/NSTEMI).  So, that sounds favorable.

But, the real reason there’s no significant differences in outcomes – and the reason why they terminated the trial early – is because the interim data is underpowered to detect a difference.  As you see, the 30-day mortality is 12% vs 11% in favor of placebo – and that wasn’t helping NovoNordisk, so they quit before they could reach sufficient statistical power to prove their product was unhelpful.  However, they can now benefit from that same lack of power to detect differences by applying it to the safety aspect, and trumpeting its equivalency in terms of AEs.

When taken in the context of the original trial, this is just a flawed piece of pharmaceutical propaganda to try and prevent the building crackdown on off-label Factor VII use.

http://www.ncbi.nlm.nih.gov/pubmed/21610529