Month: July 2014

Build a New EDIS, Advertise it in Annals for Free

As everyone who has switched from paper to electronic charting and ordering has witnessed, despite some improvements, many processes became greatly more inefficient.  And – it doesn’t matter which Emergency Department information system you use.  Each vendor has its own special liabilities.  Standalone vendors have interoperability issues.  Integrated systems appear to have been designed as an afterthought to the inpatient system.  We have, begrudgingly, learned to tolerate our new electronic masters.

This study, in Annals of Emergency Medicine, describes the efforts of three authors to design an alternative to one of the vendor systems:  Cerner’s FirstNet product.  I have used this product.  I feel their pain.  And, I am in no way surprised these authors are able to design alternative, custom workflows that are faster (as measured in seconds) and more efficient (as measured in clicks) for their prototype system.  It is, essentially, a straw man comparator – as any thoughtful, user-centric, iterative design process could improve upon the current state of most EDIS.

With the outcome never in doubt, the results demonstrated are fundamentally unremarkable and of little scientific value.  And, it finally all makes sense as the recurrent same sad refrain rears its ugly head in the conflict-of-interest declaration:

Dr. Patrick and Mr. Besiso are employees of iCIMS, which is marketing the methodology described in this article.

Cheers to Annals for enabling these authors to use the pages of this journal as a vehicle to sell their consulting service.

“Efficiency Achievements From a User-Developed Real-Time Modifiable Clinical Information System”
http://www.ncbi.nlm.nih.gov/pubmed/24997563

Dueling PE Meta-Analyses

A guest post by Rory Spiegel (@EMNerd_) who blogs on nihilism and the art of doing nothing at emnerd.com.

Nothing sparks controversy quite like a discussion on the utility of thrombolytics. No sooner had the wave of debate brought on by the publication of the PEITHO trial and its finding of no overall mortality benefit died down, did JAMA stoke these flames with the publication of a meta-analysis including the entirety of the literature on thrombolytic use for pulmonary embolism. Examining 16 trials, the authors found a statistically significant absolute mortality benefit of 1.12% or an NNT of 59 patients. This benefit was offset by the increase in major bleeding events observed in those given thrombolytics (9.24% vs 3.42%) with a 1.27% absolute increase in ICH.



The cascade of incendiary events continued when one week later a second meta-analysis examining the very same question was published in Journal of Thrombosis and Haemostasis. Only these authors claimed to find the exact opposite of their JAMA counterparts. In this case the authors found no statistical improvement in mortality in the patients given thrombolytics when compared to those given a placebo. Despite these contradictory claims, a more comprehensive inspection reveals these meta-analyses are extensively saying the same thing. A comparison of the two serves as a timely reminder that conclusions reached from any meta-analysis is primarily dependent on the trials selected for inclusion.  The JAMA meta-analysis included 2115 patients in 16 trials, while the Journal of Thrombosis and Haemostasis examined only 1510 patients in 6 trials. Interestingly, the absolute risk reduction in mortality was 1.12% in the JAMA publication vs 1.4% in the Journal of Thrombosis and Haemostasis publication. Though the JAMA analysis had an overall smaller absolute risk reduction, the result reached statistical significance due to the larger sample size.



More importantly the results of these publications should not come as a surprise. Before the publication of PEITHO the data on thrombolytics for PE was sparse. Most of the trials suffered from small sample sizes and questionable methodology. It is the amalgamation of these small trials that accounts for the mortality benefit in both meta-analyses. In the JAMA publication the mortality difference consisted of 17 fewer deaths in the thrombolytic arm compared to the placebo. All of which originated from these small underpowered studies. Conversely, the two large high quality trials (PEITHO and MSPPE) consisting of 1005 and 256 patients respectively made up the majority of patients meta-analyzed, neither of which found a mortality benefit with the use of thrombolytics. Moreover the 2% absolute increase in ICH seen in the PEITHO cohort is only diluted by the inclusion of these small trials, whose sample sizes were not powered to detect such rare events. A more elegant design would be to utilize a weighted average or one of the various statistical methods that takes into account each study’s sample size and event rate, allocating a greater weight to the hardier cohorts. Though one might argue an equally elegant solution would be to not include such flawed trials in the first place.


The publication of these dueling meta-analyses highlights the flaws of such statistical endeavors. Small trials with flawed methodological designs are prone to fall victim to publication bias and the fluctuating whims of chance. Collecting this data and attaching a statistical judgment to it does not correct these imperfections, it augments them. The overall benefit of thrombolytics in PE is yet undetermined, but the answer will not be elucidated in such analysis. We require further large randomized controlled trials like the PEITHO trial. Adding small flawed cohorts to this robust dataset does nothing but muddy the already murky waters.

“Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.”
http://www.ncbi.nlm.nih.gov/pubmed/24938564

“Impact of the efficacy of thrombolytic therapy on the mortality of patients with acute submassive pulmonary embolism: a meta-analysis.”
http://www.ncbi.nlm.nih.gov/pubmed/24829097

Lives Saved … or Profiteering by Overdiagnosis?

Following an initial acute ischemic stroke, a search for the cause must be undertaken – for small vessel vasculitis, atherosclerotic emboli, thrombi from the systemic circulation, and so forth, beyond the domain of the Emergency Physician.  However, what the Emergency Physician does encounter is the sequelae of this search, in the form of oral anticoagulants.

These two articles from the New England Journal of Medicine, on their own, seem to reflect advances in diagnostic yield following acute ischemic stroke or transient ischemic attack.  The authors point out approximately 25% of patients suffering AIS and half of those suffering TIA never receive an ultimate identified etiology for stroke – and are classified as “cryptogenic”.  The authors in each of these studies suppose this may be due to the paroxysmal nature of atrial fibrillation, and that short-term electrocardiographic monitoring is missing this diagnosis.  In each study, some type of long-term monitoring technology is utilized, and, ultimately, the rate of diagnosis for paroxysmal atrial fibrillation jumps from 1-3% in each cohort to 8-12% in each cohort.

The catch – scads of authors for each report conflict-of-interest with both manufacturers of novel oral anticoagulants, or device manufacturers likely related to continuous ambulatory monitoring.  There is clear benefit to each of these parties, considering potential expanded indication for both monitoring and for anticoagulation.  These articles will likely be used to support both activities, despite not measuring any patient-oriented benefit.  How much of a primary or recurrent stroke risk is attributable to these very-infrequent paroxysms of atrial fibrillation?  Do they benefit equally from anticoagulation?

Given the conflict-of-interest enshrined in these articles, I am certain the advertised presumption will be they do.  They may, of course, be right – or, this may turn into yet another example of overdiagnosis and high-cost, low-yield medicine.

“Atrial Fibrillation in Patients with Cryptogenic Stroke”
http://www.nejm.org/doi/full/10.1056/NEJMoa1311376

“Cryptogenic Stroke and Underlying Atrial Fibrillation”
http://www.nejm.org/doi/full/10.1056/NEJMoa1313600

Independence Day History Lesson

July 4th, for our worldwide readers, is Independence Day in the United States.  This means the trauma centers fill up with all manner of traumatic and alcohol-related injuries.  Just as the Founding Fathers intended.

However, for your reading enjoyment today, I give you the medical biography of John Jones, the first Professor and Chair of Surgery in the American Colonies – as part of the group establishing the Columbia University College of Physician and Surgeons in 1767.

“John Jones, M.D.: pioneer, patriot, and founder of American surgery.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860285/ (free full text in PubMed Central)

How Much Money Is Wasted By Endovascular Treatment for Stroke?

If you recall, last year was a bumper crop of prospective, randomized, controlled trials testing the efficacy of endovascular devices versus tPA alone for acute ischemic stroke.  These trials – SYNTHESIS, MR-RESCUE, and IMS-III – were unified by demonstrating no additive benefit.  Of course, these trials proved nothing to proponents of endovascular therapy, owing to the “outdated” devices used.

Interestingly, IMS-III also prospectively gathered costs associated with both treatment modalities.  Presumably, the authors expected to show a treatment advantage despite increased costs, and would follow-up with a cost-effectiveness analysis.  Now, since there was no advantage with endovascular treatment, this is simply a fascinating observational report.

So, how much did everything cost?  The answer, like everything in medicine:  depends on who’s paying.  Hospital charges for patients receiving tPA were a mean of $86,880, with a median of $58,247, and ranged from $13,701 to $830,652.  Hospital charges for endovascular treatment would have been a mean of $113,185, with a median cost of $86,481, and ranged from $23,350 to $552,279.  Thankfully, this is the funny money that few patients are realistically expected to pay.  Costs, on the other hand, are based off the negotiated Medicare reimbursements, and were estimated at a mean cost of $25,630 for IV tPA and $35,130 for endovascular therapy.  So, a fair bit of extra cost to the system for a therapy that isn’t providing any proven benefit.

Given the lack of efficacy and increased costs, you’d think it should be obvious we ought not be deploying endovascular therapy widely – but, clearly, this is unfortunately not the case.  Medicare and Medicaid still reimburse for endovascular interventions – and its use is bolstered by its sponsors and other such propaganda in the NEJM.  Until proven otherwise, this is all simply money down the drain.

“Drivers of Costs Associated With Reperfusion Therapy in Acute Stroke: The Interventional Management of Stroke III Trial”
http://stroke.ahajournals.org/content/early/2014/05/13/STROKEAHA.113.003874.abstract