Monday, October 20, 2014

The Trauma Pan-Scan Saves Lives

… and redeems them for valuable prizes.

Such is the message of this systematic review and meta-analysis, evaluating the published literature comparing “whole body CT”, arbitrary complete scanning, with “selective imaging”, scanning as indicated by physical examination.

Identifying seven studies, comprising 23,172 patients, these authors found a 20% reduction in mortality – 20.3% versus 16.9% – associated with the use of WBCT, despite a higher mean Injury Severity Score in the WBCT cohort.  The implication: choosing a selective scanning strategy was harmful, even in the face of a less-injured cohort.  Thus, the authors conclude the mortality advantage far exceeds any risks from radiation, and WBCT should be considered the standard method of evaluation.

Except, all but 2,610 of the patients in these pooled studies are from retrospective cohorts fraught with selection bias.  There are many reasons why trauma patients with lower ISS might yet have higher mortality, and otherwise aggressive diagnostic evaluation not indicated.  And, when those retrospective patients are tossed out, the comparison is a wash in the prospectively studied cohort.

If you’re a fan of selective imaging, this study probably changes little in your mind.  If you’re a fan of WBCT, it’s another citation to add to your quiver.  The authors of this study are hoping REACT-2 gives us the definitive answer – but with only 1,000 patients, I doubt that will be the case, either.

“Whole-body computed tomographic scanning leads to better survival as opposed to selective scanning in trauma patients: A systematic review and meta-analysis”
http://www.ncbi.nlm.nih.gov/pubmed/25250591

Friday, October 17, 2014

Clinical Informatics Exam Post-Mortem

I rarely break from literature review in my blog posts (although, I used to make the occasional post about Scotch).  However, there are probably enough folks out there in academia planning on taking this examination, or considering an Emergency Medicine Clinical Informatics fellowship – like the ones at Mt. Sinai, BIDMC, and Arizona – to make this diversion of passing interest to a few.

Today is the final day of the 2015 testing window, so everyone taking the test this year has already sat for it or is suffering through it at this moment.  Of course, I’m not going to reveal any specific questions, or talk about a special topic to review (hint, hint), but more my general impressions of the test – as someone who has taken a lot of tests.

The day started out well, as the Pearson Vue registration clerk made a nice comment that I’d gone bald since my picture at my last encounter with them, presumably for USMLE Step 3.  After divesting myself of Twitter-enabled devices, the standard computer-based multiple-choice testing commenced.

First of all, for those who aren’t aware, this is only the second time the American Board of Preventive Medicine has administered the Clinical Informatics board examination.  Furthermore, there are few – probably zero – clinicians currently taking this examination who have completed an ACGME Clinical Informatics fellowship.  They simply don’t exist.  Thus, there is a bit of a perfect storm in which none of us have undergone a specific training curriculum preparing us for this test, plus minimal hearsay/experience from folks who have taken the test, plus a test which is essentially still experimental.

Also, the majority (>90%) of folks taking the test use one of AMIA’s review courses – either the in-person session or the online course and assessment.  These courses step through the core content areas describe for the subspecialty of Clinical Informatics, and, in theory, review the necessary material to obtain a passing score.  After all, presumably, the folks at AMIA designed the subspecialty and wrote most of the questions – they ought to know how to prep for it, right?

Except, as you progress through the computer-based examination, you find the board review course has given you an apparently uselessly superficial overview of many topics.  Most of us taking the examination today, I assume, are current or former clinicians, with some sort of computer science background, and are part-time researchers in a subset of clinical informatics.  This sort of experience gets you about half the questions on the exam in the bag.  Then, about a quarter of the course – if you know every detail of what’s presented in the review course regarding certification organizations, standards terminologies, process change, and leadership – that’s another 50 out of 200 questions you can safely answer.  But, you will need to really have pointlessly memorized a pile of acronyms and their various relationships to get there.  Indeed, the use of acronyms is pervasive enough it’s almost as though their intention is more to weed out those who don’t know some secret handshake of Clinical Informatics, rather than truly assess your domain expertise.

The last quarter of the exam?  The ABPM study guide for the examination states 40% of the exam covers “Health Information Systems” and 20% covers “Leading and Managing Change”.  And, nearly every question I was trying to make useful guesses towards came from those two areas – and covered details either absent from or addressed in some passing vagueness in the AMIA study course.  And, probably as some consequence of this being one of the first administrations of this test, I wasn't particularly impressed the questions – which were heavy on specific recall, and not hardly on application of knowledge or problem solving.  I'm not sure exactly what resources I'd use to study prior to retaking if I failed, but most of the difference would come down to just rote memorization.

However, because the pass rate was 92% last year, and nearly everyone taking the test used the AMIA course, an average examinee with the average preparation ought yet to be in good shape.  So, presumably, despite my distasteful experience overall – one likely shared by many – we’ll all receive passing scores.

Check back mid-December for the exciting conclusion to this tale.

Wednesday, October 15, 2014

TMJ Dislocations: A Better Mousetrap?

Anterior temporomandibular dislocations are generally quite satisfying closed reductions.  Patients, understandably, are exceedingly grateful to have their function restored.  However, it typically requires parenteral analgesia, sometimes procedural sedation, and puts the practioner at risk of injury from inadvertent biting.

This interesting pilot describes a technique in which the patient, essentially, self-reduces the TMJ dislocation by using a syringe held between the posterior molars as a rolling fulcrum.  I’d describe it in more detail, but I think, from the image reproduced here, you’ll get it:


These authors used this technique for 31 cases, and only one was ultimately unsuccessful.

While this is not the intended use for a syringe, I can’t hardly imagine any terrible harmful adverse effects from materials failure – and they don’t exceed the risks of procedural sedation.  I certainly find it reasonable to experiment with this technique.

“The ‘Syringe’ technique: a hands-free approach for the reduction of acute nontraumatic temporomandibular dislocation in the Emergency Department.”
http://www.ncbi.nlm.nih.gov/pubmed/25278137

Monday, October 13, 2014

Who Loves Tamiflu?

Those who are paid to love it, by a wide margin.

This brief evaluation, published in Annals of Internal Medicine, asks the question: is there a relationship between financial conflicts-of-interest, and the outcomes of systematic reviews regarding the use of neuraminidase inhibitors for influenza?  To answer such a question, these authors reviewed 37 assessments in 26 systematic reviews, published between 2005 and 2014, and evaluated the concluding language of each as “favorable” or “unfavorable”.  They then checked each author of each systematic review for relevant conflicts of interest with GlaxoSmithKline and Roche Pharmaceuticals.

Among those systematic reviews associated with author COI, 7 of 8 assessments were rated as “favorable”.  Among the remaining 29 assessments made without author COI, only 5 were favorable.  Of the reviews published with COI, only 1 made mention of limitations due to publication bias or incomplete outcomes reporting, versus most of those published without COI.

Shocking findings to all frequent readers, I’m sure.

“Financial Conflicts of Interest and Conclusions About Neuraminidase Inhibitors for Influenza”
http://www.ncbi.nlm.nih.gov/pubmed/25285542

Original link in error ... although, it's a good article, too!
http://www.ncbi.nlm.nih.gov/pubmed/24218071

Friday, October 10, 2014

More CT Coronary Angiography Dreaming

CT coronary angiography has been touted as a lovely test for the acute setting – a relatively fast, non-invasive method of obtaining information on the coronary vasculature with reasonable-sounding diagnostic characteristics.  However – despite what these authors seem to be trying to convey – it’s simply a test, not a protective intervention.

This is a prospective longitudinal cohort study of 585 individuals at a single institution undergoing CT coronary angiography for suspected ischemic chest pain.  Patients with negative troponins were enrolled during weekday, daytime hours, had TIMI 0-4 (mostly 0-2), and absent the usual contraindications to CTCA.  Patients were followed for nearly two years – and, of 506 patients with zero or insubstantial plaque seen on CTCA, all were still alive, and none had suffered an acute coronary syndrome.  Thus, the fantastic protective effect of a negative CTCA.

The only issue – all those patients would have achieved such event-free survival whether they underwent CTCA or not.

Of the 79 admitted for invasive angiography with severe stenosis, only 34 received PCI or CABG, and 10 were found to have less than 40% stenosis.  So – ultimately – 585 CTCAs to identify the 6% of patients who may potentially have benefited, harming just as many with invasive procedures and the remainder with radiation.  There is a reasonable, ultimate question regarding whether those with negative evaluations are obviated from additional chest pain work-up over the long run – but that has yet to be demonstrated in practice, and the costs associated with the initial false positives subtract from those future potential savings.

Rather than demonstrate the utility of CTCA in the Emergency Department, these authors better demonstrate the unfortunate characteristics of its overuse.

“Long-term Outcome after CT angiography in Patients with Possible acute coronary syndrome”
http://www.ncbi.nlm.nih.gov/pubmed/24738614

Wednesday, October 8, 2014

Using Patient-Similarity to Predict Pulmonary Embolism

Topological data analysis is one of the many “big data” buzzphrases being thrown about, with roots in non-parametric statistical analysis, and promoted by the Palo Alto startup, Ayasdi.  I’ve done a little experimentation with it, and used it mostly to show the underlying clustering and heterogeneity of the PECARN TBI data set.  My ultimate hypothesis, based on these findings, would be that patient-similarity is a more useful predictor of individual patient risk than the partition analysis used in the original PECARN model.  This technique is similar to the “attribute matching” demonstrated by Jeff Kline in Annals, but of much greater granularity and sophistication.

So, I should be excited to see this paper – using the TDA output to train a neural network classifier for suspected pulmonary embolism.  Using 152 patients, 101 of which were diagnosed with PE, the authors develop a topological network with clustered distributions of diseased and non-diseased individuals, and compare the output from this network to the Wells and Revised Geneva Scores.

The AUC for the neural network was 0.8911, for Wells was 0.74, and Revised Geneva was 0.55. And this sounds fabulous – until it’s noted the neural network is being derived and tested on the same, tiny sample.  There’s no validation set, and, given such a small sample, the likelihood of overfitting is substantial.  I expect performance will degrade substantially when applied to other data sets.

However, even simply as scientific curiosity – I hope to see further testing and refinement of potentially greater value.

“Using Topological Data Analysis for diagnosis pulmonary embolism”
http://arxiv.org/abs/1409.5020
http://www.ayasdi.com/_downloads/A_Data_Driven_Clinical_Predictive_Rule_CPR_for_Pulmonary_Embolism.pdf

Monday, October 6, 2014

Does Cardiac Catheterization Help After OHCA?

Yes!

Probably.

It sure seems like it.

But, we still don’t really know for whom.

We’ve reviewed several of the prospective and retrospective studies regarding post-arrest cardiac catheterization on this blog over the years.  The general conclusion – the authors are very enthusiastic about their outcomes, but their comparison groups are invalidated by selection bias.  So, unsurprisingly, when a systematic review and meta-analysis of these studies is performed – the same critiques hold.

This review identifies 50 studies with sufficient reporting and design for analysis.  27 of these studies describe use in STEMI complicated by OHCA – and outcomes are largely excellent, compared to typical OHCA survival.  Good neurologic survival, in the 18 studies reporting such, averaged 68.4%.  There’s not much debate regarding STEMI complicated by OHCA – cardiac catheterization, when available.

The problem, however, arises when evaluating patients with OHCA and no clear cause for arrest.  There were 15 studies comparing outcomes with and without cardiac catheterization – and, overall, good neurologic outcome was present in 58% versus 35.8%, with and without cardiac catheterization, respectively.  However, 11 of these 15 studies were retrospective, and patients undergoing conservative management tended to have poorer prognosis at baseline and those who underwent cardiac catheterization tended to have more prominent ischemic changes on post-arrest ECG.

So, it’s another garbage-in, garbage-out sort of meta-analysis and review.  It cannot be used to support universal expansion of the target population for cardiac catheterization after OHCA, and tells us, essentially, what we already knew.  Clearly, some patients – particularly those for whom a culprit lesion is identified – benefit.  For the remainder, the treatment population remains unclear, particularly in the face of the extraordinary resource utilization.

“Cardiac catheterization is associated with superior outcomes for survivors of out of hospital cardiac arrest: Review and meta-analysis”

Friday, October 3, 2014

ARISE, and Cast Off the Shackles of EGDT

The sound you hear is a sigh of relief from Emergency Physicians and intensivists regarding the outcomes of the Australasian Resuscitation in Sepsis Evaluation (ARISE).

As ProCESS suggested, and as many have suspected all along, it seemed the critical intervention from Early Goal-Directed Therapy was the early part – and less the SCO2 monitoring and active management of physiologic parameters using dobutamine and blood transfusion.  Now, we have a second study, in addition to ProCESS, supporting the same general conclusions.

ARISE enrolled patients with confirmed or suspected sepsis, and either hypotension refractory to 1L crystalloid fluid challenge or a lactate level of 4.0 mmol/L or more.  31 centers randomized 1,600 patients to undergo either EGDT or “usual care”, which entailed routine local clinical practice, excepting measurement of SCVO2 was forbidden.  EGDT, however, was provided by specially coordinated teams to ensure all patients received the intervention.  The primary outcome was death from any cause within 90 days, powered to detect an absolute risk-reduction of 7.6%.

Baseline characteristics between the two groups were quite similar, few patients dropped out of each arm, and, finally, there was no difference in the primary outcome – 18.6% vs. 18.8% (does it matter which is which?)  Indeed, of all the outcomes measured, only two differed in statistically significant fashion: the EGDT cohort departed the Emergency Department 30 minutes more quickly, and the EGDT cohort received greater vasopressor support – attributable entirely to the use of dobutamine in 15.4% of patients vs. 2.6% in the usual care arm.

As expected, resource utilization unique to EGDT, of course, was different – more and different types of central venous catheters, more arterial catheters, and more frequent use of blood products.  And, as we’re seeing – all of this is unnecessary.  As with ProCESS, “usual care” has become EGDT, excepting these elements.  Both groups received substantial, early crystalloid resuscitation, early appropriate antibiotic coverage, and departed the Emergency Department to a critical care setting quite quickly.

EGDT receives credit for making us aware the impact early identification and intervention can have on mortality.  However, it is time to leave EGDT behind and identify new resuscitation targets and sensible strategies for achieving them.

“Goal-Directed Resuscitation for Patients with Early Septic Shock”
http://www.nejm.org/doi/full/10.1056/NEJMoa1404380

Thursday, October 2, 2014

Blood is Good for the Injured Brain - Or is it?

A guest post by Dr. Andrew Kirkpatrick (@AskEMdoc), an Emergency Medicine resident at the University of Texas Medical School at Houston.

Hypoxia, of course, is lethal to vulnerable cells.  Erythropoeitin, in many small trials, has been shown to be neuroprotective after injury.  So, given these apparently obvious beneficial and synergistic treatments, the authors of this study set out to answer the question: What happens when a patient with Traumatic Brain Injury (TBI) is given blood and erythropoietin?

This is a randomized control trial with a factorial (2x2) design that tested Erythropoietin (Epo) versus Placebo and Transfusion Threshold of 7.0g/dL versus 10g/dL to determine if either of the above interventions conferred the benefit of improved neurologic recovery in TBI.  A total of 200 individuals with TBI were randomized into one of four groups using a block randomization strategy, sorting individuals into groups with and without transfusion thresholds or Epo administration.  Both the treatment team and the follow up personnel were blinded to Epo administration, but only follow up personnel could be blinded to transfusion threshold group.  Then, to make this study even further convoluted, the Epo dose and frequency was changed mid-stream due to safety concerns, dividing the Epo arm into the Epo1 and Epo 2 groups.   They also changed the study from a superiority trial to futility, and unusually selected 0.15 as their one-tailed alpha – a choice severely restricting their ability to reject the null hypothesis.

Determination of primary outcome data was completed utilizing the Glasgow Outcome Scale (GOS) using a variety of strategies, including in person and phone follow up.   For all comparisons – both transfusion thresholds and Epo – no statistically significant difference was detected.  Given their small sample, they may simply have been unable to produce a difference – as Epo seemed to potentially have some beneficial effect, though transfusion certainly showed no such signal.  Risk of death, infection, ARDS, and Cardiovascular complications including VTE were evaluated for as well, and both Epo groups and the 10g/dL transfusion group had significant increased risk of adverse events.  And, regarding resource utilization, the transfusion threshold group obviously consumed more blood products.

The study had several limitations including change in Epo protocol with 1/3 of the patients already enrolled, inability to blind clinicians to transfusion threshold, the aforementioned statistical limitations, and generalizability limitations owing to its enrollment at only two trauma centers.  Overall the results were unable to demonstrate benefit to either strategy – but were able to demonstrate definite harms.  Until further evidence is presented, it is prudent to continue conserving blood products and abstaining from giving ineffective, expensive medication.

“Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury A Randomized Clinical Trial”
http://www.ncbi.nlm.nih.gov/pubmed/25058216

Wednesday, October 1, 2014

Preposterous Inpatient Antibiotic Overuse

It is one matter entirely to give antibiotics for self-limited bacterial or viral conditions.  It is another matter to regularly, simultaneously prescribe multiple, redundant antibiotics with overlapping coverage, excepting a few particular situations.

And, we are clearly using overlapping coverage far more than just a few particular exceptions.

This review of proprietary data from inpatient antibiotic use in 505 U.S. hospitals between 2008 and 2011 looked at three types of antibiotic overlap – that for MRSA, for anaerobic bacteria, and for ß-lactam therapy.  These authors noted 32,507 cases in which patients received at least two consecutive days of redundant, simultaneous antibiotics.  The largest offender, by far:  82,018 days in which patients received both intravenous metronidazole and intravenous piperacillin-tazobactam.  The majority of the remainder were also anerobic overlap, and the authors also cited over a thousand cases each of dual-MRSA therapy or dual-ß-lactam therapy.

Now, there are certain tissues in which vancomycin has poor penetration, and vancomycin-intermediate strains are increasing – so it’s unreasonable to say all dual-MRSA therapy is inappropriate.  The same applies to the dual-ß-lactam therapy, as double-coverage for pseudomonas and other MDR pathogens frequently requires at least initial redundant therapy.  However, I think this data still reasonably reflects an abundance of opportunity to curtail inappropriate antibiotics use.

The authors, mostly employed by a health services consulting company, also try to do a cost-analysis to quantify the scope of the redundant use.  Unfortunately, in each case, they assume the more expensive antibiotic is the redundant one – which inflates and exaggerates their estimates.  Presumably, this comes out of the need to subsequently promote their company’s services, and these numbers are best ignored.

But, we can, at least, do much better than our present state of affairs.

“Economic Impact of Redundant Antimicrobial Therapy in US Hospitals”
http://www.ncbi.nlm.nih.gov/pubmed/25203175