Author: Ryan Radecki

Everything is a Poison…

…when taken in inappropriate amounts.

The NYT reports on a recent AHRQ release that doesn’t tell us a lot that’s new – more hospital and ED visits are coded with medication side effects – a “50% increase since 2004”.  The problem with the lay article is that it focuses on these issues as “medication errors” as some alarming decline in quality in U.S. healthcare.  Part of the problem with this release is that it’s simply data – it’s not a study or a statistical analysis that attempts to control for other confounding influences – have the number of prescriptions for each of these classes gone up?  What’s the average age of these patients presenting with errors (i.e., aging boomers)?  There are a lot of other factors contributing to whether a medication results in an adverse effect, and they aren’t just “errors”.  The ED data isn’t all that insightful, although it is interesting to see how it differs from the inpatient errors.  The #1 culprit for the ED is “Other”, which is 261k compared to 118k opiate adverse events – which basically invalidates their data when most of your data points fall into an unknown category.

Heparin-Binding Protein for Bacterial Meningitis

This study came out highlighted by the last Emergency Medicine Journal Watch.

Now, I don’t want to steal Emergency Medical Abstracts thunder, since I’m sure they’re going to tear this article to shreds in a few months, but let me just comment on the conclusion of the Journal Watch reviewer that this is a “promising new biomarker that…might play the same role in bacterial meningitis that D-dimer does in venous thromboembolic disease” and that “an HBP level >20 ng/mL should prompt empirical therapy for bacterial meningitis” like this assay is something we should incorporate into our practice.

Part of the problem with this study is their methodology.  They used HBP to diagnose bacterial meningitis…in patients where they could diagnose bacterial meningitis.  Which means, these are all patients in which they already were able to make the diagnosis of bacterial meningitis without this magical new test.  So, immediately from that standpoint, it doesn’t add any value.

They also used two different samples, including, apparently, some they had on file from a decade ago – but their justification seems reasonable.

They compare the sensitivity and specificity of their test to the sensitivity and specificity of CSF polynuclear cells and CSF WBC count – and they’re statistically identical.  And, specifically, they are marginally better in absolute terms and likely in AUC vs. any of those tests individually, but when taken against the combined information given by all the CSF tests we already send off, there is likely no clinical difference.

Lastly, the most important words are on the first page: “Hansa Medical AB has filed a patent application on the use of HBP as a diagnostic tool in meningitis.  Dr. Linder, Dr. Christensson, Dr. Björck, and Dr. Åkesson are listed as inventors.”

My conclusion: this is an unnecessary test to add to your arsenal.  Read the article, make your own conclusion.

http://www.ncbi.nlm.nih.gov/pubmed/21200320

Dexamethasone in Asthma

Steroids are part of the mainstay of therapy for acute exacerbations of reactive airway disease – but does it matter which steroid we use?

I think it’s clear that answer is: “no”.  Multiple studies support using dexamethasone rather than prednisone – best described in pediatrics, but this study reaffirms its utility in adults.  The advantage is its half-life of 72 hours, meaning it requires fewer doses and, in theory, greater compliance.  Although, really, this study is limited directly as a pharmacologic comparison study specifically because of the compliance issue – there’s no guarantee every patient finished their course of prednisone, while it’s pretty likely patients managed to take at least the 2nd non-placebo dose of their dexamethasone.  However, in terms of clinical relevance – it reflects the compliance issues encountered in reality.

There’s an underpowered single-dose dexamethasone pediatric study out there, as well, which appears promising.  I like the idea of 100% compliance guaranteed by a single-dose in the ED, but it’s something that needs more data.

www.ncbi.nlm.nih.gov/pubmed/21334098

Emergency Response Teams

This is an idea that sounds great in theory – if you have a roving team of skilled resuscitation professionals in your hospital assisting nurses who are concerned about their patients, you can intervene on these patients before they deteriorate, keep people from escalating into the ICU, and improve outcomes.  It’s such a great idea that the entire country of Australia has been spurred into implementing these.  My hospital has them, and, no doubt, many other hospitals do as well.

The problem is, they’re having a hard time demonstrating their efficacy.

A study out of Stanford last year reported that, at their VA hospital, implementation of emergency response teams (ERTs) reduced mortality.  Unfortunately, on closer reading, ERTs reduced mortality on the floor, and their primary intervention was to move people to the ICU – where their mortality was no longer counted in the study.  While it is rather graceless to have people coding and dying on the floor, unfortunately they did not show the outcomes they claimed.

http://www.ncbi.nlm.nih.gov/pubmed/20624835

This more recent report, from Australia, as mentioned above, is a before and after analysis of hospital-wide mortality, CPR rates, etc. with their ERTs.  They likewise show benefits, with ICU admissions, CPR rates, and mortality all declining after implementation.  However – and they very astutely point this out themselves – one of the most significant functions of the ERTs was to clarify code status and affirm a greater number of people as DNR or futile resuscitation.  While this function, if it reduces ICU admissions, is absolutely a cost and resource savings, I don’t think it’s precisely how they wanted to justify implementation of ERTs.

There are many reasons to have ERTs, but a mortality and cost-benefit justification has not yet been well-demonstrated.

http://www.ncbi.nlm.nih.gov/pubmed/21411218

News Flash – Better Electronic Medical Records Are Better

In this article, providers are asked to complete a simulated task in their standard EMR – which is Mayo’s LastWord supplemented by Chart+ – vs a “novel” EMR redesigned specifically for a critical care environment with reduced cognitive load and increased visibility for frequently utilized elements and data.  In their bleeding patient scenario, their novel EMR was faster and resulted in fewer errors.  So, thusly, a better EMR design is better.

While it seems intuitively obvious – you still need studies to back up your justification for interface design in electronic medical records.  Their approach in testing is one I’d like to see expanded – and perhaps even implemented as a regulatory standard – evaluation on cognitive load and a certain level of task-based completion testing with error rates at a certain level.  Electronic medical records should be treated like medical devices/medications/equipment that should be rigorously failure tested.  While EMRs are far more complicated instruments, studies such as this one, illustrate that an EMR with interfaces designed for specific work environments to aid in effective and efficient task-completion save time and reduce errors.

The main issue I see with EMR these days is that the stakeholders and motivators behind this initial wave of implementation in financial – systems in place to capture every last level of service provided to a patient in order to increase revenues.  Now, the next generation and movement with EMRs is to look at how they can increase patient safety, particularly in light of threats of non-payment for preventable medical errors.  Again, financial motivation, but at least this financial motivation is going to motivate progress and maturation of medical records as tools to protect patients, not simply to milk them for profits.

http://www.ncbi.nlm.nih.gov/pubmed/21478739

Chest Pain and Recent Negative Stress Test

If your hospital is anything like our hospital, you have tons of low- and intermediate-risk chest pain.  Every one is stressful, but hopefully you have a friendly hospitalist, or better yet, an ED-run chest-pain unit that gives you a place for observation admissions.  They go there, get their rule-out, and get some sort of provocative test, as discussed in the most recent AHA guidelines.  The test is negative, they go home.

…and then they come back a week later with the same symptoms.

This is a great paper to have in your pocket when you need to justify why this patient still needs to be ruled out; I heard about it when it was mentioned on the April EM:RAP during the low-risk chest pain discussion.  Patients with negative stress tests may still be diagnosed with CAD on angiography – 20.7% incidence of CAD in their cohort which had negative or non-diagnostic stress within 3 years – and 7.8% were diagnosed with AMI.

When you add negative troponins and the negative stress from the previous visit, you’ve met the guidelines and standard of care to say they did not have acute myocardial ischemia and you cannot induce ischemia on provocative testing, and they are risk-stratified into a group of patients very unlikely to have ACS in the next 30 days/60 days/6 months.  However, you get that high NPV because you’re performing these tests on a low-risk population, not because the sensitivity of those tests, particularly stress testing, is good enough.  While this patient likely does not need another provocative test – although, depending on individual factors, they may be candidates for angiography of some sort – if their story is concerning for cardiac etiology, they still need enzymatic rule-out.

http://www.ncbi.nlm.nih.gov/pubmed/21079714

Prehospital STEMI Diversion to PCI

Time is muscle and the earlier you get to PCI the more muscle you can save.  So, we should just drive by all the critical access hospitals and go straight to PCI-capable centers?  The Dutch, in this retrospective study, think we should.  Everything in their protocol hinges on EMS reading a computer interpretation of the EKG, and, if it says STEMI, they go to the PCI center.  At the end of the day, everyone who went to the PCI capable center first rather than the spoke hospital first had a mortality benefit between 2% and 2.6% at one year.  


What they really don’t discuss much are the outcomes of the 5.7% of their intention-to-treat analysis that had false positives.  False positives, at least, are typically not harmful to the patient – the alternative diagnoses for chest pain that would benefit from immediate treatment at one of their non-PCI “spoke” hospitals are probably not that frequent – aortic dissections and submassive PEs tend to be the sorts of things that would benefit.  But, even if they did a true intention-to-treat analysis, they’d probably still have a mortality benefit.  The other problem with false positives is the financial costs associated with unneeded cath lab activation and the costs to the system associated with taking EMS out of service.  It’s obvious that treating patients for their disease in the most timely fashion for certain diseases improves outcomes – but we must always beware of the unintended consequences.


http://www.ncbi.nlm.nih.gov/pubmed/21315209


This is actually a big deal sort of topic in EM right now as it relates to the regionalization of care, which is something that the Academic Emergency Medicine consensus conference is dealing with right now.  Attempting to mirror what’s happened with trauma networks, they’re trying to extend the benefits to other acute conditions that otherwise benefit from transfer to higher levels of care.  Clearly, a myriad of life-threatening conditions benefit from the resources of tertiary referral centers – but the logistics and political issues associated with centralizing care for different conditions remains a significant barrier.


http://www.ncbi.nlm.nih.gov/pubmed/21122020

Sodium Nitroprusside with CPR

Here’s another interesting piece of animal literature to fight with your IRB about for performing studies on human subjects in your ED.  The article itself is a little hard to follow because of the terminology used – eCPR, SNPeCPR, and S-CPR, but, essentially, they have regular CPR, then they have their enhanced CPR which consists of an impedance device and compressive trousers, and then they have enhanced CPR plus sodium nitroprusside.  Additionally confounding, on top of different CPR methods, they only gave standard CPR epinephrine, while the other two methods received no epinephrine.  Sodium nitroprusside pigs did much better than the other two methods and medications.
So, with n = 8, in pigs, there’s only a couple statistical conclusions we can make.  Their pigs that received their no-drugs enhanced-CPR did no differently than standard CPR with epinephrine.  Then, their pigs that received sodium nitroprusside plus enhanced-CPR do way better than their no-drugs enhanced-CPR.  So, sodium nitroprusside is doing something.  As far as external validity, 1) it’s pigs and 2) it’s probably financially and logistically infeasible for our ACLS-equipped paramedics to go through the additional steps of enhanced-CPR.  I’d really like to see what would have happened in a blinded, three-arm, nitroprusside vs. epinephrine vs. placebo where each group had the same CPR.
That being said, if you can get your IRB to approve a prospective study in human subjects – more power to you.  All the literature shows our current ACLS is mostly useless – and the definition of insanity is doing the same thing over and over again and expecting different results – so I’m all for looking at new agents in cardiac arrest.

http://www.ncbi.nlm.nih.gov/pubmed/21358401

Carbapenem Resistant Bacteria in India

More public health doom and gloom from the infectious disease world – multiple bacterial found carrying stable and transmissible plasmids for the NDM-1 gene, a form of beta-lactamase that endows bacteria with carbapenem resistance.  In the sewage.  And in the drinking water.

…but only South Asia, for the time being.  But, they also note that India is a popular destination for “medical tourism” to save money on surgical procedures, and patients have returned as carriers for bacteria with the NDM-1 gene.
This is not a unique development – there’s MDR tuberculosis, inducible clindamycin resistance for MRSA, and, my favorite, macrolide-resistant streptococcus.  Macrolide resistance in streptococcus can be directly linked to the overuse of azithromycin, a patient-friendly drug with terrible pharmacokinetics.  In contrast to the medication it replaces, erythromycin, it has such a long half-life (68 hours when multiple doses are administered) after you take your fifth dose that it spends a long period in the body below its therapeutic concentration, just sitting there as substrate to induce resistance without bacteriostatic properties.
Grim.

Antibiotics for Acute Otitis Media

These are two articles coming to us from January’s NEJM – one from Pittsburgh and one from Finland.  For a ridiculously prevalent disease managed daily in the ambulatory setting by thousands of providers across the world, we really don’t know what we’re doing.  Firstly, we know there are bacteria in the middle ear – plenty of studies have aspirated out a variety of pathogens.  Secondly, undertreated AOM may lead to suppurative complications – the surgical emergency of mastoiditis.  Finally, however, we also know the natural history of AOM is to resolve without intervention and treatment in most cases.

The commentary accompanying these articles seemed to think these two studies tilted the balance in favor of routine antibiotic use for AOM.  And, you can read the articles in that fashion – the Finnish article makes an argument that by their standard of care, the placebo group had 45% treatment failure and required antibiotic rescue 30% of the time.  However, I read the article and their definitions of treatment failure are, for the most part, not clinically relevant.  A red ear that still looks red on day three does not predict much – and, actually, a lot of their primary outcome measures were not statistically significant until they added in the 30% they used rescue treatment on to boost their definition of treatment failure.  So, this study doesn’t tell much much – except that Augmentin causes diarrhea 40% of the time.

The Pittsburgh study reads much more straightforward and, partially, justifies my criticism of the Finnish study.  By day 7, 80% of their Augmentin group had symptom improvement compared to 74% of their placebo group.  However, the ears still looked terrible in the placebo group – but, obviously, weren’t correlating with symptoms.  So, is it clinically relevant to define treatment failure based on the appearance of the ear?  I would say that improvement in symptoms is the appropriate measure of clinical cure – and in that respect, the 80% vs 74% numbers match up better with previously published literature.

To me, these articles don’t help.  I don’t necessarily mind the AAP recommendations of treating AOM with antibiotics under a year of age – although, really, after their third set of immunizations, it’s not as though this is going to be a nidus for SBI.  Clearly, antibiotics offer some advantage – but not to everyone.  When I have a three year-old I have to hogtie to get a one-second glimpse at a red TM, how do I know whether this is a patient whose AOM will resolve on its own, or whether he falls into the subset of patients who will derive benefit from antibiotics?  And, is that 6% absolute difference in clinical outcome worth giving 40% of children horrible diarrhea (not that anyone uses Augmentin first-line for AOM, anyway).  With the NNT with antibiotics to prevent one case of mastoiditis estimated at 4100 from cohort data from the United Kingdom, that’s a lot of useless (and harmful) antibiotic prescriptions.  If we want to reduce the amount of antibiotic resistance in this country, I think these studies support a conservative non-antibiotic strategy initially in appropriately selected patients.

http://www.ncbi.nlm.nih.gov/pubmed/21226577
http://www.ncbi.nlm.nih.gov/pubmed/21226576

Addendum 5/11: Scott Weingart & David Newman did a bit of a rant on this topic on the most recent EM:RAP where they attacked the Pittsburgh article specifically regarding result reporting integrity.  Dr. Newman delved into far more detail regarding the multiple primary outcomes listed and found the original research protocol listed only time to resolution of symptoms as the primary outcome – which was statistically equivalent between the two groups.  He and Dr. Weingart seem to suggest there was not sufficient editorial oversight regarding the publication of this article due to these flaws, and that the author’s conclusions are suspect to the point of disingenuous.