Not a day goes by, it seems, the New York Times or some other equally prominent journalistic source publishes a scathing invective regarding the irresponsible cost of healthcare in the U.S.  In this context, it is equal parts highly entertaining and appalling to measure how ignorant Emergency Physicians are regarding the cost of the care they provide.

This single-center study performed in Philadelphia gives results similar to prior work in the same vein.  23 attending physicians and 21 residents were surveyed regarding estimates of cost of care for 102 of their patients discharged from the Emergency Physician.  Each estimate for the total cost of care was compared with the actual final charges billed to the patient or their insurance carrier.

Median estimated charge:  $1,268
Median actual charge:  $2,175

There was no difference between attending and resident performance.

Not an encouraging result – particularly as patients are likely going to be burdened with ever-increasing portions of their healthcare costs, and we ought to be able to communicate with them the cost of care as part of shared decision-making in the Emergency Department.

"Emergency physicians’ knowledge of the total charges of medical care"
www.ncbi.nlm.nih.gov/pubmed/23685055

This is a, yet another, study in Stroke of folks claiming it is "safe" to use thrombolysis on patients who are found to have suffered a stroke while sleeping – the so-called "wake-up stroke" population.

The specific claim made is "This retrospective analysis of data in thrombolysed consecutive acute ischemic stroke patients shows no significant differences in mortality, functional outcomes, or bleeding rates between WUIS patients with no early ischemic change on CT and those treated within 4.5 hours of stroke onset."

...because their sample size is so small the absolute differences are still within the statistical variation expected by chance.  This is, unfortunately, a recurring theme I see in these stroke publications, many of which are retrospective registry reviews.  Their groups are statistically not different, but this is owing to failed statistical power in study design, as opposed to clinically meaningful equivalence.  This is a major difference between retrospective and prospective studies – in which prospective studies choose specific absolute differences necessary to define clinically meaningful equivalence, and then perform power and sample size calculations based on these constraints.

Their outcomes are, incidentally, also simply terrible.  They publish a figure comparing outcomes with their wake-up stroke population to their 0-4.5 hour thrombolysis reference group – a 326 patient reference group with 18% mRS 0-1 and a 26% mortality.  But then, they further break out the 197 patients from that group that received tPA within the ECASS III license criteria, showing that compliance with guidelines leads to 32% mRS 0-1 and 18% mortality.  This therefore implies the other 129 patients – the ones who received tPA outside the license criteria – had utterly dismal functional outcomes and frighteningly high mortality.

Someone needs to go down to King's College and check up on them and make sure all this off-label use isn't just costly killing fields.

"A Case-Controlled Comparison of Thrombolysis Outcomes Between Wake-Up and Known Time of Onset Ischemic Stroke Patients"
http://www.ncbi.nlm.nih.gov/pubmed/23723307

"High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes."

Jerry Hoffman has mentioned the exercise to, while reading, expand any instance of the word "may" to "may or may not" – to help erase the positive bias of speculative conclusions.  And, this is one of those perfect circumstances where the lukewarm endorsement from this abstract conclusion ought to be predicated with a pound of cautionary conditionality.

These authors call their study SAMURAI-ICH, and it's a prospective, observational study regarding the safety of early blood pressure reduction in intracerebral hemorrhage.  What this really means is they thought aggressive BP lowering was going to be awesome – despite only having various bits of inconclusive evidence – so they made wholesale practice changes, and then started a registry to monitor outcomes.  So, you can see the bias already.

And, verily, there is an association between their ability to lower blood pressure in ICH and favorable outcomes.  Now, their "favorable outcomes" cohort was also young, less disabled at baseline, and had smaller ICH hematoma volume.  Through the magic of statistical models, they attempt to control for all the various prognostic catastrophes, and thusly they arrive at their significant association.

But, finally, this observation doesn't in the slightest explain whether the blood pressure control improved outcomes – or whether it was simply easier to lower blood pressure in patients whose cerebrovascular physiology was less deranged by smaller insults, and who went on to have good outcomes.  Aggressive antihypertensive treatment "may or may not" ameliorate clinical outcomes, indeed.

Beware observational conclusions!

"Systolic Blood Pressure After Intravenous Antihypertensive Treatment and Clinical Outcomes in Hyperacute Intracerebral Hemorrhage : The Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study"
www.ncbi.nlm.nih.gov/pubmed/23704107

Although ranting is fun, I much prefer pointing readers in the direction of useful, educational articles – and dispensing with the lighthearted vitriol.

Today, I don't have to gripe about JAMA – because they've published a succinct and fair assessment of the new highly-sensitive troponins by Dr. Lemos from UT Southwestern.  Written for a general audience, he begins with, essentially, a case example of mismanaged Type II MI resulting from non-specific troponin rise, and then progresses through the various confounding causes of elevated troponins and the definition of myocardial infarction.  He then proceeds to frame these problems in the context of ruling out ACS and balancing sensitivity and specificity, as I've previously covered here, here, and here.  He makes a fine point that expanding use of these assays will mean approaching the troponin measurement as a continuous value, rather than dichotomous, and a more nuanced diagnostic process.  He also cautions against over-testing and over-diagnosis in the low-risk population.

He also half-proposes the use of troponin testing in the outpatient setting, as elevated baseline troponin levels are associated with poor prognosis.  However, he notes it remains uncertain the effect routine measurement might actually have on cost-effective care and outcomes.

The author discloses conflict-of-interest with several firms, including manufacturers of the highly-sensitive assays – but his conclusion is quite restrained, and acknowledges the very real practice limitations.

"Increasingly Sensitive Assays for Cardiac Troponins" 
jama.jamanetwork.com/article.aspx?articleid=1693870‎

Some of the most common practices in Emergency Medicine are only weakly tested or defined – including steroids for acute respiratory illness.  What is the true minimum effective dose?  How many days – 3, 5, 7, or 14?  Burst or taper?  Much of our practice is based on habit and mimicry, along with the general evidence that, despite ourselves, we don't seem to be doing much harm.

This is the REDUCE trial, a multi-center, randomized, double-blind, non-inferiority comparison between a 5-day and a 14-day course of 40mg oral prednisone for acute COPD exacerbation.  And...it found no difference in the primary outcome measure.  So, then, all's well.

Except, their outcome measure is utterly bizarre – re-exacerbation within six months?  I cannot fathom how a 1-2 week period of steroids could have any causative association with outcomes more than a handful of half-lives after cessation of treatment.  Perhaps they theorize the short-term steroid exposure is insufficient to avoid long-term damage secondary to the acute inflammation? 

There are also some potentially confounding differences in baseline characteristics.  There were 9% more smokers and 5% more home oxygen in the short-term treatment group – which could favor conventional treatment – but 4% fewer conventional patients were on daily steroids during the treatment period and 8% fewer conventional patients received concurrent antibiotics – which could favor the short-term treatment group.  Some of these differences would have more effect on short-term outcomes, while others would affect long-term outcomes.  I don't know if there are true clues in the Kaplan-Meier curves they present – because the sample size is small enough these variations might just be occurring due to chance – but it appears there's a possible hazard towards early re-exacerbation in the 5-day group, followed by regression towards equivalence by six months.

However, these issues aside, their conclusion is probably valid.  Their predefined threshold for non-inferiority was 15% – and they easily cleared that bar.  All the confounders are probably not of significant magnitude to affect the overall result at that threshold – even for shorter, more relevant follow-up time periods.  Additionally, this is otherwise consistent with the other evidence that short-courses of steroids are absolutely acceptable in this context.

"Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease"
www.ncbi.nlm.nih.gov/pubmed/23695200

The self-described "EM Nerd" Rory Spiegel from Newark Beth Israel writes in to point out a fascinating discovery – previously undiscovered clinical trial results for Kcentra, the newly available 4-Factor Prothrombin Complex Concentrate, embedded in the product labeling.

4-factor PCCs are well-known from their use in Europe – capable of rapid reversal of factor-dependent coagulopathy at the expense of increased thrombotic complications.  Within the package labeling, however, two new Phase III trials are described – open-label, randomized, non-inferiority comparisons.  The trials, for what they're worth, show no significant outcome difference compared with FFP – but, yet again, no clinically relevant threshold for non-inferiority is established to drive sample size calculations.  I'd like to comment more, but they only provide detailed adverse event information on one of the two trials.  Perhaps we'll see these published and peer-reviewed imminently.

It should also be noted the extensive exclusion criteria used to enroll patients in these studies – a far longer list than the few contraindications listed on the package label.  These criteria may be noted on the ClinicalTrials.gov site.

Lovely to see we've now another costly reinvention of the wheel that will almost certainly be overutilized at the behest of Bering's marketing army.

"Efficacy and Safety Study of BERIPLEX® P/N Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy"
http://clinicaltrials.gov/ct2/show/NCT00708435

"The Sign of Four…"
http://emnerd.tumblr.com/post/50947148065/the-sign-of-four

"CSL Behring 1.14.1.3 Draft Labeling Text"
http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM350239.pdf

The AAP has guidelines for simple febrile seizure – "There, there, the frightening demonic possession your child just experienced is nothing to worry about."  Complex febrile seizures, however, are offered far less conclusive guidance.

This little retrospective review from UC San Diego evaluates 193 patients presenting with complex febrile seizure.  Lumbar puncture was performed in 136, and 1 patient ultimately received a diagnosis of bacterial meningitis.  The authors suggest, cognizant of the limitations, that complex febrile seizures need not routinely undergo LP.

This is entirely reasonable and consistent with the prior literature.  The largest retrospective review, from Boston Children's, identified 3 cases with bacterial meningitis out of 526 children.  A systematic review and meta-analysis identified 41 cases of bacterial meningitis out of 1996 children.  There are additional cases of viral meningitis and encephalitis in these cohorts as well – of uncertain clinical significance – but the general implication is that otherwise well-appearing children ought not need LP absent other signs of CNS infection.

It would, of course, be fabulous if a consensus guidelines would further reinforce this evidence.

"Necessity of Lumbar Puncture in Patients Presenting with New Onset Complex Febrile Seizures"
www.ncbi.nlm.nih.gov/pubmed/23687537

"Yield of lumbar puncture among children who present with their first complex febrile seizure."
www.ncbi.nlm.nih.gov/pubmed/20566610‎

"Risk of bacterial meningitis in young children with a first seizure in the context of fever: a systematic review and meta-analysis."
www.ncbi.nlm.nih.gov/pubmed/23383133‎

There have been dueling schools of thought regarding atraumatic intracerebral hemorrhage: let the brain autoregulate its own blood supply and don't artificially lower the blood pressure, or use intravenous agents to lower blood pressure because there's evidence it decreases hematoma expansion.  However, until now, there'd been no evidence that decreased hematoma size correlated with meaningful patient-oriented outcomes.

So, what are they saying about INTERACT2, the open-label, randomized trial of intensive BP control (SBP <140 mmHg) versus guideline-concordant BP control (<180 mmHg)?

@medwireNews INTERACT2 contradicts "longstanding dogma", supports intensive BP reduction in ICH #eurostroke2013 

@MedscapeNeuro INTERACT2: Intensive Blood Pressure Lowering Benefits ICH 

@IctusClnic #ESCLondon2013 Surely INTERACT2 will have a great impact in blood pressure management after intracranial hemorrhage.

Pfffft.

The primary outcome was reduction in death or major disability (modified Rankin scale 3 to 6) at 90 days.  Unadjusted outcome was statistically negative, 52.0% to 55.6% (OR 0.87, 95% CI 0.75 to 1.01), but favoring intensive BP control.  Their secondary outcomes, which uses the conceptually messy tool of ordinal analysis, essentially magnified the effect of that 3.6% absolute difference in mRS outcomes and goes on to show that folks with less disability end up happier and more functional.

However, the baseline functional characteristics favored the intensive BP group, with median NIHSS score of 10 vs. 11.  68% of the cohort was from China – which has uncertain effects on external validity.  Over seven different intravenous antihypertensives – including the most popular agent, urapidil – were used for BP lowering, further muddling precise treatment guidance.  Most ICH was small volume hemorrhage, and BP treatment didn't seem to have much different on hematoma expansion – so it's hard to say why the intensive control group seemed to have a trend towards superiority.

And, finally, even though approximately half of the 1436 assigned to guideline-recommended treatment group had baseline systolic BP >180 mmHg, only 303 of them received an anti-hypertensive agent within 1 hour of study assignment.  It might be more appropriate to describe this study as "intensive" vs. "poorly guideline-concordant" BP control – would outcomes have been more favorable if more of the guideline-concordant group actually had their systolic BP lowered below 180 mmHg?

In any event, to call this a practice-changing paradigm is a only a half-truth.  It does appear safe, at least, to make a brisk and reasonable effort to lower BP in atraumatic, intracerebral hemorrhage.  Whether "intensive" control is needed with a nicardipine infusion, such as in the upcoming Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II trial, is still uncertain.

"Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage"
http://www.nejm.org/doi/full/10.1056/NEJMoa1214609

The authors of this article make several discrete claims regarding the utility of coronary CT angiography – simply stated right in the title of the article:  "Routine coronary computed tomographic angiography reduces unnecessary hospital admissions, length of stay, recidivism rates, and invasive coronary angiography in the Emergency Department triage of chest pain".  And, essentially all the assertions made in this observational, retrospective review are suspect.

Reduces unnecessary hospital admissions:
The article in no fashion addresses "unnecessary" hospital admissions.  After all, of their selected cohort of patients, a tiny fraction – 9 of 1,788 – ruled-in for acute MI.  A total of 42 underwent revascularization, but this is a measure reflecting only the aggressiveness of their local cardiology groups.  It would seem the real problem regarding "unnecessary" admissions is an inability to select patients with appropriate clinical probability for further evaluation.

Reduces length of stay:
There is a less than 1 hour reduction in length of stay only for discharged ED patients.  A true accounting of the LOS and congestion of chest pain patients ought to include admitted patients who depart the ED for their hospital observation bed soon after their initial biomarker result – but that would probably make their overall result contrary to their chosen narrative.  The reduction in length of stay is also influenced by the authors exclusion of patients who had ED LOS less than 3 hours – as the authors simply decide no adequate evaluation of low-risk chest pain patients could be performed in that timeframe.

Reduces recidivism rates:
The reduction in recidivism rates may have reached statistical significance, but the absolute difference was only 20 patients, most of whom were discharged from the Emergency Department.

Reduces invasive coronary angiography:
There is a reduction in coronary angiography – mostly, from what I can tell, in that the handful of patients with multi-vessel disease detected on CCTA were referred to CABG, and the use of invasive coronary angiography was obviated.  The absolute difference was only 19 angiography episodes – an avoidance of a handful of $2000-$3000 procedures at the cost of nearly a thousand $700-$1200 CCTAs.

Finally, their abstract conclusion claims it reduces healthcare resource utilization:
The authors never explicitly define this endpoint – which is probably for the best, as I count 960 non-invasive and 8 invasive tests in their CCTA cohort versus 368 non-invasive and 27 invasive tests in their "standard evaluation" cohort.  The admission rate, however, is more than halved from 40% to 14%.  A reduction in resource utilization would be contrary to general consensus from trials of CCTA versus standard care.

Most disturbingly, this article reports "Disclosures: none".  However, a simple internet search reveals multiple authors having prior relationships with Siemens and GE Healthcare.  Perhaps by some narrowest definition this isn't untruthful, but it is certainly misleading.

"Routine coronary computed tomographic angiography reduces unnecessary hospital admissions, length of stay, recidivism rates, and invasive coronary angiography in the Emergency Department triage of chest pain"
http://www.ncbi.nlm.nih.gov/pubmed/23684682

There are two problems with blood cultures.  The first question is with regard to the likelihood you'll get a true positive result.  That question is covered by this JAMA Rational Clinical Examination.

The second question regards whether the true positive result is clinically meaningful.  This retrospective review of 639 cellulitis patients – 325 without medical comorbidities and 314 with – evaluated for changes in therapy as a result of positive cultures.  46 cultures returned positive – with half being judged due to contaminants.    Of the 23 true positives, 5 resulted in a change of antibiotic therapy - only 2 of which expanded the initial antibiotic choice to include coverage for a new pathogen.  Both changes in therapy occurred in the immunosuppressed group.

Yet another example of the incredibly low yield of an expensive test.  We're clearly simply asking a question for which we already have the answer.

"Blood culture results do not affect treatment in complicated cellulitis"
www.ncbi.nlm.nih.gov/pubmed/23588078

So far, we've seen nothing but poor outcomes in endovascular cerebral reperfusion trials.  The MERCI devices were simply dysfunctional and lethal and, despite advances with newer devices, we're still waiting for a decisive trial demonstrating clear benefit.  But, the money is out there for the taking if the science will support it – and thus, more "science".

This is a study involving authors sponsored by Stryker who do a retrospective review of cases at two hospitals, comparing infarct volume and short-term outcomes of patients who underwent either endovascular intervention, conventional thrombolysis, or no treatment for their large-vessel acute ischemic stroke.  The accompanying editorial probably sums up their limitations best:
"Retrospective, nonrandomized nature of the study; the comparison between 2 hospitals in the same health care system in which endovascular interventions were performed in one and not the other, which may have resulted in some unintentional differences in overall care; the combining of data among patients who received intravenous thrombolysis with those who received no reperfusion therapy, which may have diluted treatment responses; ... and the lack of long-term clinical outcomes that could be correlated with the imaging findings."

So, they have a collection of patients for whom it is in no way appropriate to compare outcomes and generalize any sort of conclusions – and that's precisely what they do.  And, specifically, after reporting full-cohort baseline characteristics, their conclusions are based on subgroups of that cohort – and using an imaging surrogate outcome measure!

I'd tell you these authors conclude patients with an NIHSS of 14 or higher may be the best candidates for endovascular reperfusion therapy – but then I'd be further perpetuating this "science".  Again, what they claim may be true – but they're overestimating the ability of their data to claim it.

"Comparison of Final Infarct Volumes in Patients Who Received Endovascular Therapy or Intravenous Thrombolysis for Acute Intracranial Large-Vessel Occlusions"
http://archneur.jamanetwork.com/article.aspx?articleid=1686897

We've all seen folks come in via EMS with mechanical devices performing automated chest compressions.  These probably do a lovely job of freeing up paramedics from performing uninterrupted CPR, but their relationship to outcomes has been typically uncertain.

This meta-analysis and systematic review, however, reports these devices are superior to manual chest compression – with an OR of 1.6 towards increased return of spontaneous circulation.  Considering the copious evidence towards improved outcomes by minimizing interruptions during CPR, this would be an important finding, and tailors nicely with the expected advantage of mechanical compression devices.

However, this COI statement covering each of the four authors might also be in some fashion related to the positive results reported here:
"Dr. Westfall has received modest research grant support from ZOLL Medical Corporation. Mr. Krantz has received significant research grant support from ZOLL Medical Corporation. Mr. Mullin has served as a consultant for ZOLL Medical Corporation. Dr. Kaufman is an employee of ZOLL Medical Corporation."

Unsurprisingly, these authors also demonstrate one of the overlooked evils of meta-analyses – the obfuscation of source COIs.  This JAMA article from 2011 does a lovely job describing this critical problem, and, as expected, these conflicted authors ignore the pervasive sponsorship bias present in their selected review.  Additionally, half the articles are only conference abstracts, suffering from results and methods not subject to the same level of rigorous peer review.

It really ought to be rather embarrassing for the editors of this journal to be approving such a clearly flawed vehicle – essentially blatant advertising for their $15,000 medical device – for publication.  No better, Journal Watch Emergency Medicine gives this article a bland and un-insightful thumbs-up.

"Mechanical Versus Manual Chest Compressions in Out-of-Hospital Cardiac Arrest: A Meta-Analysis"
www.ncbi.nlm.nih.gov/pubmed/23660728‎

I am biased – I helped set the Pediatric Emergency Care Applied Research Network up back as a research assistant peon before medical school – so it always pleases me to report on PECARN's newest outputs.

This is a preplanned sub-analysis of their massive observational pediatric blunt trauma study.  Their pediatric blunt trauma decision instrument, unfortunately, turned out to not be terribly useful.  This data on the outcomes of patients with negative abdominal CT scans, at least, ought to help us.

Of the 3,819 patients enrolled with normal abdominal CTs following blunt trauma, 6 went on to have clinically significant abdominal injuries requiring intervention.  They provide a lot of detail about the patient population, but their conclusion is pretty simple: don't routinely admit these trauma patients for observation to try and catch that 0.02%.  If there's no other indication for admission, they may be discharged with appropriate symptom return precautions.

"A Multicenter Study of the Risk of Intra-Abdominal Injury in Children After Normal Abdominal Computed Tomography Scan Results in the Emergency Department"
www.ncbi.nlm.nih.gov/pubmed/23622949

It remains a noble endeavour to attempt to identify the risk of serious bacteria infections in children.  That said, many have tried, and many have failed.

These authors from the Netherlands and the United Kingdom try, yet again.  They note the best performing decision instrument incorporates 26 variables – which they feel is unworkably unwieldy in a clinical setting – and attempt to derive their own, tighter instrument.  Unfortunately, the clinical variables that shake out of their prediction methodology all have odds ratios less than 6 – leading to a prediction model that can be calibrated only either for horrible sensitivity or horrible specificity.  The sensitive model will lead to over-testing of an otherwise well population, and the specific model will essentially pick up only the cases that were clinically obvious.

It's becoming pretty clear over the years that attempting to reduce the number of discrete clinical variables in the febrile SBI decision-instrument is a dead-end strategy.  Complex clinical problems simply defy dimension reduction.  Furthermore, the true test of a decision instrument also ought not just be statistical evaluation in a vacuum, but comparison with clinical judgement.


"Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study"
www.bmj.com/content/346/bmj.f1706

It's pretty clear that children shouldn't be receiving CT scans, whenever possible.  Despite this, the rate of CT for the diagnosis of pediatric appendicitis continues to rise.
This is a retrospective review from the Medical University of South Carolina that describes their implementation of an imaging protocol designed to encourage ultrasound use.  They report before-and-after statistics for their protocol – and, unsurprisingly, they're pro-ultrasound.
Their protocol is generally simple – if it's clinical appendicitis, consult surgery.  If it's uncertain, do ultrasound first – if ultrasound equivocal, do CT.  If the patient appears unwell, skip ultrasound and do CT to evaluate for perforation.  Their institution started out with 82% of patients undergoing appendectomy having received CT, with this percentage dropping to 20% following implementation of the protocol.  Their negative appendectomy rate was stable at 5% after implementation, as well.  They also note the cost of a pediatric CT is $6500 compared with ultrasound at $1100.
The main disadvantage of their protocol was the low sensitivity exhibited by ultrasound – 61% – and the length of stay resulting from patients who required both ultrasound and CT – nearly 8 hours.  Considering ultrasound sensitivity depends on the experience of the operator, efforts to implement this strategy might benefit from upgrading local ultrasound capabilities.
"Clinical Practice Guidelines for Pediatric Appendicitis Evaluation Can Decrease Computed Tomography Utilization While Maintaining Diagnostic Accuracy"
www.ncbi.nlm.nih.gov/pubmed/23611916‎

Every so often, we're referred a patient from the hematology clinic for prophylactic platelet transfusion when their infusion center is full.  As these authors state, it is common practice to routinely prophylactically transfuse platelets in the presence of severe thrombocytopenia.

And, the abstract conclusion here is:  "The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis."

This conclusion is the dubious interpretation of a combined endpoint of uncertain clinical significance.  Their primary endpoint was the summation of WHO 2, 3 and 4 bleeding.  Nearly all their bleeding was WHO 2 – essentially, troublesome, but self-limited bleeding not requiring transfusion.  With regards to major bleeding, the per-protocol rates were 5/258 in the no-prophylaxis group and 1/230 in the prophylaxis group – falling short of statistical significance, but reasonably clinically significant.

There was a 0.2 unit PRBCs per patient difference in transfusion between the prophylaxis group and the no prophylaxis group.  There was, obviously, a 1.3 unit platelets per patient difference between groups.  Hospitalization days were similar.  No patient died from bleeding.  One patient in the prophylaxis group suffered a transfusion-related anaphylactic event.

So, yes – platelet transfusions reduce bleeding.  I'm just not certain these authors have demonstrated the net benefit – given 66 patients receiving prophylactic transfusions, 1 fewer non-fatal important bleeding event.  Clinically insignificant net PRBC difference, significantly higher usage of platelet transfusions.  I think there is plenty of room to debate cost and benefit – particularly considering interesting hypothesis-generating subgroup variation.

The authors declared multiple conflicts-of-interest, although it's not clear to me if any of them would be relevant to the current study.

"A No-Prophylaxis Platelet-Transfusion Strategy for Hematologic Cancers"
http://www.nejm.org/doi/full/10.1056/NEJMoa1212772

Are you interested in making your AMI diagnostic evaluation even less specific?  Good!  Because Brahms Thermo Fisher et al want to sell you a rapid copeptin assay to help with that.

Copeptin is a stable, terminal portion of the arginine vasopressin peptide.  This peptide is released from the pituitary in response to cardiovascular hemodynamic stress and has a theoretical role in the diagnosis of acute myocardial infarction.  The advantage copeptin may have over conventional troponin assays is detectable release in circulation preceding troponin.

In 1971 patients collected through their multi-center trial, 156 were diagnosed with AMI (7.9%).  Upon presentation to the Emergency Department, 40 were STEMI.  281 patients had cTnI greater than 40ng/L, 97 of whom were subsequently diagnosed with nSTEMI.  1646 had cTnI less than 40ng/L, 19 of whom eventually were diagnosed with nSTEMI – a miss rate of 1.1%.  Pretty good – but, obviously, we practice in a zero-miss world.  Adding copeptin to this troponin-negative population with a cut-off of 14pmol/L decreased the miss rate to 0.5%.  The specificity, of course, was useless – only 10 of 493 patients with positive initial copeptin and negative inital troponin went on to receive a diagnosis of nSTEMI.

So, the question is – would a negative copeptin change your practice?  Is there a clinically important difference between a 1 in 100 miss rate vs. a 1 in 200 miss rate?  These authors think adding copeptin to troponin will allow you to discharge a patient after the inital biomarker result – but I think this minimal incremental improvement in diagnostic performance doesn't change whatever pathway the patient was already on, nor add much to a discussion of shared decision-making with the patient.  They also don't address a performance advantage compared to high-sensitivity troponin assays (which have, of course, their own issues).

These authors are pretty high on copeptin – but, then again, many of them are employed by or sponsored by the manufacturers of the copeptin assay.

"Copeptin Helps in the Early Detection Of Patients with Acute Myocardial Infarction: the primary results of the CHOPIN Trial"
http://www.ncbi.nlm.nih.gov/pubmed/23643595

My recently-published short invited response in Proto Magazine, a Massachusetts General Hospital publication, to an article on the state of current medical journals:  "Probing Deeper"

They did, however, unexpectedly edit out a portion of my response – an entire paragraph originally between the current 2nd and 3rd paragraphs:

In 2005-2006, The Lancet derived 41% of its revenue through sales of over 11 million reprints.[1]  The NEJM, which published more industry-funded studies thanThe Lancet – 78% vs. 58% – undoubtedly derives even more.[2]  Ironically, Jeffery Drazen, editor-in-chief of NEJM, is quoted as saying "Our most important job is vetting information.”  Dr. Drazen infamously failed to do so when privy to information regarding increased mortality in rofecoxib's (Vioxx) VIGOR trial – a publication for which NEJM sold Merck 900,000 reprints.[3][4]

And, here are my references:

The prevailing notion has been that women present with symptoms of angina that are "atypical" from men – headaches, jaw pain, generalized malaise – rather than definitive anginal-type chest pain or pressure.  These authors would like to suggest this global characterization is incorrect.

These authors enrolled a sample of 128 men and 109 women who underwent coronary angiogram following an abnormal stress test.  Patients with obstructive coronary artery disease on their angiogram were surveyed regarding the symptoms that prompted them to seek care.  Of this cohort, 89 men had obstructive disease compared with 50 women.

Overall, there was no significant statistical difference in the rate of most descriptors used by men or women.  Surprisingly, women were statistically more likely to use "typical" terms such as "discomfort", "crushing", "pressing" and "aching" to describe their chest pain.  Therefore, these authors conclude the clinical construct of "atypical angina" in women is incorrect.

I would tend to agree – excepting their study suffers from selection bias.  If patients are only referred for testing due to suspected coronary artery disease, then the population with "atypical" symptoms might not be fully captured.  That being said, it does look as though the female population in their study encompassed a number of patients who potentially were referred for atypical symptoms, considering the yield of their coronary angiography was much lower in women.  It would have been interesting to compare the referral symptoms to the subset with demonstrated obstructive CAD.

"Reconstructing Angina: Cardiac Symptoms Are the Same in Women and Men"
www.ncbi.nlm.nih.gov/pubmed/23567974‎

These authors address a real problem: which coughing adults have pneumonia?  Unfortunately, after evaluating 2,820 of them – they still don't really know.
This is an interesting article because it pulls together a symptom profile along with two of the other non-specific inflammatory markers being touted as important diagnostic tools: CRP and procalcitonin.  Primary care physicians enrolled adults presenting with acute cough, and used plain radiography as their gold standard for diagnosis of pneumonia.
In short:

• "Symptoms and signs" suggestive of pneumonia (fever, tachycardia, abnormal lung exam) all had positive OR between 2.0 and 5.3, and combined offered an AUC of 0.70.
• Adding CRP as a continuous variable to symptoms and signs gave an OR of 1.2 and increased the AUC to 0.78.
• Adding procalcitonin as a continuous variable to symptoms and signs gave an OR of 1.1 and increased the AUC to 0.72.

Using CRP as a dichotomous cut-off at 30 mg/L, in addition to the independent symptom predictors, gave them the discriminating ability to produce a low, intermediate and high risk group: 0.7%, 3.8%, and 18.2% chance of pneumonia.  A high-risk group where fewer than one in five have the disease?  The authors recommend consideration of empiric antibiotic therapy in this group, but I prefer their other recommendation to consider radiography as confirmation in this subset.  The remainder ought to be candidates for observation, as false positives and harms from additional testing are likely to outweigh true positives.
Again, refuting the terrible JAMA distortion, procalcitonin had no useful discriminatory diagnostic value.

Last year, I noted a study concerning a report of excess deaths associated with azithromycin use.  This study, a retrospective, observational cohort from Tennessee Medicaid data suggested a death rate double that of other antibiotics.  This led to the FDA issuing a warning regarding azithromycin use.
I thought all this fuss was absurd – the data quality was one step above junk and the absolute magnitude of the proposed harms was trivial.
Now, we have the counterpoint – a retrospective, observational cohort from Denmark, using their national health system database to compare prescriptions for azithromycin to penicillin V over the last 13 years.  In their cohort, there's an obvious increase in risk of death from cardiovascular causes simply from being prescribed any antibiotics – but no difference between azithromycin and penicillin V.  This seems to indicate either the systemic infectious process contributes to excess cardiovascular risk, or that respiratory symptoms are being misdiagnosed as infectious rather than cardiovascular.  The absolute effect in their propensity matched cohorts is also tiny – a handful of patients or fewer spread across a million prescription events.
The accompanying opinion seems to attempt to justify the FDA review based on the wide confidence intervals in the Danish study – the OR for death from cardiovascular causes vs. penicillin V is 1.06 (0.54 – 2.10) and doesn't statistically contradict the Tennessee study.  However, yet again, I would point to the reason behind the wide confidence intervals – the nearly trivial absolute magnitude of the harms, which amount to fractions of a patient per 1000 patient-years.

Again, plenty of reasons to responsibly reduce azithromycin prescriptions – but this cardiovascular hullabaloo probably isn't one of them.
"Use of Azithromycin and Death from Cardiovascular Causes"
http://www.nejm.org/doi/full/10.1056/NEJMoa1300799

Let the good times roll – unless, of course, those good times are cut with levamisole.

This short case report from my good friends across the street at Baylor showcases a couple lovely pictures of the purpuric and necrotizing skin lesions associated with the anti-helminth levamisole – which, for some reason, is an increasingly popular additive to cocaine.  They are quite distressing and usually present following several courses of failed outpatient antibiotics.

I don't think I specifically ever saw the exact patient these authors report upon, but it's not a unique presentation in our county healthcare system.  This article is open-access for all to view without an institutional subscription.

"Levamisole-adulterated Cocaine Induced Vasculitis with Skin Ulcerations"
http://www.escholarship.org/uc/item/4rd630zt

It's a little bit of a messy study, sadly, because it's probably a lovely idea.

These authors performed a before-and-after interventional trial in which they measured laboratory test ordering rates.  After a six-month baseline phase, the intervention phase consisted of displaying the 2008 Medicare allowable charge for a subset of frequent lab tests.  The theory, of course, is that displaying price information in the context of test ordering will alter physician behavior.

Most of the orders were placed on internal medicine services – and yes, there was a decrease in the number of orders with cost information displayed.  At the same time, however, the tests without cost information increased.  The net result, overall, was a decrease in total testing.  Interestingly, the impact seemed to mostly include a reduction by replacing CMP orders by BMPs.  $3.79 per patient-day costs were reduced during the intervention period.

So, the impact was mixed – slightly expensive tests were replaced by slightly less expensive tests.  More evaluation is necessary to determine whether these reductions have unanticipated impact on patient outcomes.

"Impact of Providing Fee Data on Laboratory Test Ordering"
www.ncbi.nlm.nih.gov/pubmed/23588900

The grass is clearly greener on the other side for these folks at Nepean Hospital in New South Wales, AUS.  This study details the before-and-after Emergency Department core measures as they transitioned from the EDIS system to Cerner's FirstNet.  As they state in their introduction, "Despite limited literature indicating that FirstNet has decreased performance" and "reports of problems with Cerner programs overseas", FirstNet was foisted upon them – so it's clear they have an agenda with this publication.

"Effect of an electronic medical record information system on emergency department performance"
www.ncbi.nlm.nih.gov/pubmed/23451963

...extremely well, in the majority of cases, according to this survey.  55.4% of physician spouses (73.2% female, 27.1% male) responded by saying they were "extremely satisfied" with their relationship, while another 31.4% were "somewhat satisfied".  Only a tiny 2.1% of spouses said they were "extremely dissatisfied" – and these numbers, as best can be reasonably compared, are very similar to the general population.

Of course, this is a survey of a subset of the Physician Masterfile that even provided an e-mail address for their spouse – so it has all sort of potential for response biases.  Regardless, it's an interesting glimpse into a few elements that seem to make for healthy relationships:

• The spouses that saw their partner less than 20 minutes a day were far less likely to be satisfied.
• Increasing hourly workweeks and nights on-call were negative influences.
• Spouses employed less than full-time seemed to be less satisfied than unemployed or full-time employed.
• Fatigue and time commitment were the greatest reported family stressors.

According to these authors, no differences were found between practice type or physician specialty ("data not shown").  Perhaps they were simply lacking statistical power, because previously published data indicated significant variability in likelihood of divorce between specialties – with psychiatry (50%) and surgery (33%) leading the pack over the base rate of general medical specialties (22-24%).

"The Medical Marriage: A National Survey of the Spouses/Partners of US Physicians"
http://www.mayoclinicproceedings.org/article/S0025-6196(12)01187-1/fulltext

While trying to summarize an evidence-based approach to pneumonia for our residency, I discovered an aimless morass that's far less helpful than originally envisioned.

"Healthcare-associated" pneumonia is a clinical entity introduced by the 2005 Infectious Disease Society of America pneumonia guidelines.  The problem with these guidelines is immediately apparent in the title – "Hospital-acquired", "Ventilator-acquired", and "Healthcare-associated" are clearly distinct in their infectious epidemiology – but this guideline lumps them all together into a single empiric treatment strategy.  They recommend triple antibiotic therapy, including double coverage for multi-drug resistant gram-negatives (pseudomonas, among others) and MRSA coverage.  This is a fine recommendation for a critically ill ventilated patient with a new lower respiratory tract infection, but preposterous overkill for an otherwise healthy patient with a short hospital stay a couple months ago.  The harms include increasing antibiotic resistance and incidence of iatrogenic end-organ damage secondary to antibiotic adverse effects.

Several articles have detailed the fallacies in this guideline and its validity in the Emergency Department setting.  Furthermore, meta-analysis of studies evaluating guideline-concordant and guideline non-concordant therapy have shown no survival advantage – as most non-concordant therapy covered the community-acquired organisms that occur with far greater regularity than the multi-drug resistant organisms in the "Healthcare-associated" cohort.

With consultation from Brian Hayes and Haney Mallemat, along with my brief literature review, this is my ad hoc approach:

1) Assess risks for MDR pathogens: recent antibiotics, recent hospitalization, poor functional status, immunosuppression.

2a) Non-severe illness and community-acquired organisms likely (low MDR risk), consider antipseudomonal fluoroquinolone monotherapy (covers some pseudomonas and atypical CAP organisms) and outpatient management.

2b) If high risk for MDR or severe illness, recommend admission with anti-pseudomonal and MRSA coverage:
 • Cephalosporin (e.g. cefepime) OR carbapenem (e.g. imipenem) OR ß-lactam/ß-lactamase inhibitor (e.g., piperacillin-tazobactam)
If severe illness, recent mechanical ventilation, or prior documented pseudomonas infection, add:
 • Antipseudomonal fluoroquinolone (moxifloxacin or levofloxacin) OR aminoglycoside (e.g. amikacin)
MRSA coverage:
 • Linezolid or vancomycin

Note these recommendations should be guided by your local antibiogram as well – at my institution, cefepime is ~90% efficatious against pseudomonas, which makes it a fine option for monotherapy.  However, our respiratory fluoroquinolones are ~70%, which makes them a less desirable choice for the monotherapy option when admitting patients.

Patients clearly do better when their causative organism is effectively covered – but we also have to be responsible stewards of our strongest antibiotics.  Given the heterogeneity of the patient cohort described in the 2005 IDSA guidelines, it's reasonable to take a stepwise approach to therapy.

"Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia"
http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/HAP.pdf

"Guideline-Concordant Antimicrobial Therapy for Healthcare- Associated Pneumonia: A Systematic Review and Meta-analysis"
www.ncbi.nlm.nih.gov/pubmed/23572322

"Guidelines for hospital-acquired pneumonia and health-care-associated pneumonia: a vulnerability, a pitfall, and a fatal flaw."
http://www.ncbi.nlm.nih.gov/pubmed/21371658/

"Healthcare-associated pneumonia is a heterogeneous disease, and all patients do not need the same broad-spectrum antibiotic therapy as complex nosocomial pneumonia."
http://www.ncbi.nlm.nih.gov/pubmed/19352176/

"Low incidence of multidrug-resistant organisms in patients with healthcare-associated pneumonia requiring hospitalization."
http://www.ncbi.nlm.nih.gov/pubmed/21463391/

This lovely editorial by Steven Green from Loma Linda succinctly summarizes the limitations of clinical decision instruments.  Decision instruments, referred to in this article as decision "rules", are potentially valuable distillations of data from large research cohorts meant to concisely address vital clinical concerns.  These include such well-known instruments as NEXUS, PERC, Centor, Alvarado, Wells, and Geneva.

He describes a need for rigorous derivation, external validation, and ease of application as important criteria.  However, the most important topics he addresses are the related issues of "1-way" versus "2-way" application and whether the rule improves upon pre-existing clinical practice.  A "1-way" decision instrument informs clinicians only when its criteria are all met – such as the PERC rule.  A patient who fails the PERC rule does not necessarily need any additional testing due to its low specificity.  The NEXUS criteria, on the other hand, is a 2-way decision rule – where its use in appropriately selected patients typically leads to radiography if its criteria are not met.

The danger, however, is the natural propensity to using a "1-way" rule like a "2-way" rule.  His example for this error is the PECARN blunt abdominal trauma article for which I previously expressed concerns.  In the PECARN blunt trauma instrument, the specificity of the derivation was actually lower than the performance of the clinical gestalt of the physicians involved.  This means the authors recommend its use only as a "1-way" rule, based on sensitivity.  However, if the cognitive error is made to apply it as a "2-way" rule, CT scanning will increase by 13%.  Then, unfortunately, if used as a "1-way" rule, the PECARN instrument only has 97% sensitivity compared with the clinician gestalt of 99% sensitivity.  This means that, if implemented as routine practice, the PECARN instrument may have a non-trivial number of misses while potentially increasing scanning.  This illustrates his point as a "poorly-designed" decision rule, despite the statistical power of the cohort evaluated.

Overall, a lovely read regarding how to properly evaluate and apply decision instruments.

"When Do Clinical Decision Rules Improve Patient Care?"
www.ncbi.nlm.nih.gov/pubmed/23548403

A brave new day dawns – clinicians who otherwise lived in fear of medicolegal reprisal from failing to administer steroids in acute spinal cord trauma may now safely withhold them.

The steroids in spinal cord debate, a one-man crusade lead by Michael Bracken, distorted by performing Cochrane Reviews of his own articles, has hopefully been definitively settled.  These authors, as part of a comprehensive update on the diagnosis and management of acute spinal cord injury, definitively summarize the flawed literature supporting methylprednisolone administration.  Their recommendation:


We've come a long way since the NIH faxed a letter to every Emergency Department in the country instructing physicians to give steroids.  Another amazing saga demonstrating the danger of inadequately reviewed medical evidence.

"Pharmacological Therapy for Acute Spinal Cord Injury"
http://www.ncbi.nlm.nih.gov/pubmed/23417182

There's probably no diagnosis in the Emergency Department that confounds residents more than the practice variation between attendings regarding the evaluation for pulmonary embolism.  Some folks send d-Dimers with reckless abandon on patients with near-zero pretest probability, others make emotional decisions to "take PE off the table" when faced with no other explanation, and then there's a group that only very rarely pursues the diagnosis.

I rarely pursue the diagnosis – mostly because the epidemiological evidence suggests we're only harming folks by making additional diagnoses of pulmonary embolism.  Therefore, in a patient who is otherwise physiologically intact, a diagnosis of pulmonary embolism is more likely to result in iatrogenic bleeding risk rather than treatment benefit.  And, then, there's the backwards fashion in which I use d-Dimer: I order it at the same time as the CTA in an otherwise intermediate- or high-risk patient, and then cancel the CTA if the d-Dimer is normal.

I use this strategy based on this prospectively collected data from the Kaiser system, published obscurely in The Permanente Journal several years back.  These authors evaluated 744 patients over 16 months who underwent CTA for rule-out PE, 347 of which had latex agglutination d-Dimer levels less than 1.0 µg/mL.  In this cohort of 347, there were seven positive scans – six of which were ultimately found to be false positives.  A handful of patients were lost, but the remainder had zero events in the three-month follow-up period.

So – d-Dimer negative, cancel the CTA, regardless of the pretest probability.  So far, so good!

"Computed Tomography Angiography in Patients Evaluated for Acute Pulmonary Embolism with Low Serum D-dimer Levels: A Prospective Study"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911823/