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/

Back in 2011, there was an article in Annals of Emergency Medicine discussing what a fantastic job we were doing in diagnosing stroke and avoiding administering tPA to "stroke mimics".  They reported a rate of 1.4% administration to stroke mimics – none of whom had bleeds.  The problem I pointed out, both on my blog and in a response letter to Annals, was that the authors invented a new category called "neuroimaging negative" acute stroke – which was probably actually all stroke mimics.  This would have changed the rate of tPA administration to stroke mimics from 1.4% to 29.3%.  The authors, having financial conflict of interest with the manufacturers of tPA, disagreed.

This study, part of the "Lesion Evolution in Stroke and Ischemia On Neuroimaging" project, evaluated the progression of lesions on MRI following tPA administration.  These authors found 231 patients with acute stroke who were initially screened by MRI prior to tPA administration and had evidence of infarction on diffusion weighted imaging.  They found that, following tPA administration, only 2 patients had resolution of an MRI DWI lesion.  They therefore conclude that "Patients with a stroke are unlikely to have complete DWI lesion reversal within 24 hours after IV tPA treatment," and patients with no DWI lesion following tPA administration should be considered to have a diagnosis other than acute stroke.

Thus, this confirms my conclusion that the 27.9% of patients from the prior study with "neuroimaging negative" acute stroke ought to universally be considered to have had a diagnosis other than acute stroke.  The reality is that we are likely treating an ever-greater number of acute ischemic strokes – and further efforts to push Emergency Physicians to treat additional patients more quickly are certainly going to expose additional patients to avoidable harms.

"Negative Diffusion-Weighted Imaging After Intravenous Tissue-Type Plasminogen Activator Is Rare and Unlikely to Indicate Averted Infarction"
http://www.ncbi.nlm.nih.gov/pubmed/23572476

Computerized Provider Order Entry – the defining transition in medicine over the last couple decades.  Love it or hate it, as UCSF's CEO says, the best way to characterize the industry leader is that it succeeds "not because it's so good, but because others are so bad."  A fantastic sentiment for a trillion-dollar industry that has somehow become an unavoidable reality of medical practice.

But, it's not all doom and gloom.  This systematic review of CPOE in use in the Emergency Department identified 22 articles evaluating different aspects of EDIS – and some were even helpful!  The main area of benefit – which has been demonstrated repeatedly in the informatics literature – was a reduction in medication prescribing errors, overdoses, and potential adverse drug events.  There was no consensus regarding changes in patient flow, length of stay, or time spent in direct patient care.  Then, on the flip side, some CPOE interventions were harmful – the effect of order set use as decision-support was implementation dependent, with some institutions seeing increased testing while others saw decreases.

A muddled look at a muddled landscape with, almost certainly, a muddled immediate future.  There are a lot of decisions being made in boardrooms and committees regarding the use of these systems, and not nearly enough evaluation of the unintended consequences.

"May you live in interesting times," indeed.

"The Effect of Computerized Provider Order Entry Systems on Clinical Care and Work Processes in Emergency Departments: A Systematic Review of the Quantitative Literature"
www.ncbi.nlm.nih.gov/pubmed/23548404

This article touches in a topic that we encounter all the time in Emergency Medicine – testing with the intent of "reassurance".  The assumption is, wouldn't a patient with a symptom concerns be less anxious regarding their illness if they received a favorable negative test result?

That assumption, according to this meta-analysis and systematic review, is wrong.  These authors gathered together 14 trials evaluating the effect of non-diagnostic testing on downstream patient outcomes.  These tests included endoscopy for mild dyspepsia, radiography for low back pain, and cardiac event recording for palpitations.  This is a difficult article to interpret, particularly because there's so much heterogeneity between the included studies, but the general conclusion is that tests performed in the setting of low pretest probability do not decrease subsequent primary care utilization, symptom recurrence, or anxiety regarding illness.

It's rarely easy to tell a patient no testing is indicated – but this is yet another example illustrating the minimal benefits to over-testing.

"Reassurance After Diagnostic Testing With a Low Pretest Probability of Serious Disease"
http://www.ncbi.nlm.nih.gov/pubmed/23440131

The correct initial diagnostic imaging test to evaluate pediatric abdominal pain for appendicitis is an ultrasound.  It carries none of the risks associated with CT imaging – except for the increased risk of a non-diagnostic evaluation.  It is also highly operator dependent, and suffers in centers without sufficient volume of abdominal ultrasonography.

This study further evaluates the subset of ultrasonography reports with the dreaded result "Appendix not visualized."  Overall, 37.7% of 662 consecutive ultrasonographic studies at the authors' institution failed to visualize the appendix.  Of interest to these authors were the "secondary signs" of appendicitis – free fluid, pericecal inflammatory changes, prominent lymph nodes, and phlegmon.

Their results are quite complicated – and, woefully, not terribly helpful.  Free fluid in females – useless.  Free fluid in males – more helpful if there's a lot, but still only 2 cases of appendicitis out of the 5 males with a moderate/large amount of free fluid.  Lymph nodes – useless.  Pericecal fat changes – 1 out of 4.  Phlegmon – 2 out of 2.

So, there's some information here.  Secondary signs with "Appendix not visualized" are typically not diagnostic alone – but, depending on the summation of other clinical findings, may yet be enough to obviate supplemental CT.

"Appendix Not Seen: The Predictive Value of Secondary Inflammatory Sonographic Signs" 
www.ncbi.nlm.nih.gov/pubmed/23528502

"The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT."

Pretty clear, eh?  This article is one of several in a line of folks working to divorce us from normal saline.  The argument is that this hypernatremic, hyperchloremic solution, when given for large-volume resuscitation in the critically ill, leads to metabolic acidosis and decreased urine output.  This study, sponsored by Baxter, the makers of Plasma-Lyte, is an open-label, before-and-after design.  One year, they gave whatever fluid they wanted – mostly saline.  The next year, saline-containing fluids were restricted, and they used 20% albumin, lactated ringers (Hartmann's solution), or Plasma-Lyte.

Firstly, the primary outcome doesn't match their clinicaltrials.gov registration.  They've changed it from mean base excess during hospital stay to two primary outcomes that weren't even both previously defined as secondary outcomes – increase in creatinine from baseline and incidence of acute kidney injury according to the RIFLE classification.

Then, they offer two positive results from their study – a decrease in the incidence of AKI and the use of renal replacement therapy.  The authors use RIFLE as their indicator of AKI – but they don't pre-define which categories of RIFLE they use, and lump "Injury" and "Failure" together to a composite endpoint to gain statistical significance.  Otherwise, it's a 7.4% control and 5.4% intervention difference in "Failure" that doesn't reach statistical significance – and considering the mean baseline creatinine was lower in the intervention period, it ought to be expected to reach the failure definition less frequently.

The difference in rise of creatinine reaches statistical significance – but they've hidden the details in their online supplement  The mean serum creatinine in the baseline period rises from 10.4 mmol/L to 11.0 mmol/L, and in the intervention period from 10.3 mmol/L to 10.7 mmol/L.  This might be statistically significant, but hardly clinically significant.  Luckily, the authors use a skewed y-axis to distort and magnify the difference in their graph of these results.

Lastly, the RRT difference reported in their six-month study period is befuddling.  The overall rate of RRT in the entire year of their baseline period is 7.9%, while the rate of RRT in the entire year of their intervention period is 7.4%.  Yet, in the six months reported for this study, they report RRT use of 10% in the baseline period and 6.3% for the intervention period.  This implies the authors retrospectively selected their study period in order to magnify the effect of the RRT difference.  This difference in RRT also doesn't match the 2% absolute difference in RIFLE classification for "failure" during the study period.  This implies the open-label nature of the study influenced the frequency of RRT use, as the authors may have exerted control over an outcome measure.

As far as patient-oriented outcomes go, after all this splitting of hairs, ICU length of stay was no different, the incidence of long-term dialysis was no different, and mortality was no different.  This is also a "bundle-of-care" study, with multiple different chloride-poor and chloride-rich fluids in use, which confounds the generalizability of the results.

Maybe chloride-sparing therapy is important.  But these authors are guilty of distorting and misleading with their presentation of results – and the JAMA editors, again, have failed us.

"Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults"
www.ncbi.nlm.nih.gov/pubmed/23073953

Credit for much of the insight into this article goes to Greg Press, who prepared this article for last month's Journal Club at UT-Houston – but he is in no way responsible for this unhinged rant.

The "tongue blade test" is one of the fun, functional tests in Emergency Medicine.  If you've got facial trauma and you're concerned about a mandible fracture, simply align a wooden tongue blade over the molars in a patient's mouth and have them bite down firmly.  Then, twist the blade medially.  If the patient is not limited by pain, they'll be able to hold the blade until it breaks.  If they're limited by pain, such as in the presence of a mandible fracture, the patient won't be able to hold the blade until it breaks.

This is an observational study enrolling 190 eligible patients for the tongue blade test in the presence of suspected mandible fracture.  66 patients had negative (normal) tongue blade tests, while 124 had positive (abnormal) tests.  All patients received a CT for definitive diagnosis.  There were 5 false negatives and 29 false positives.  Therefore, the sensitivity of the test is 95% and specificity 68%.  These results are consistent with some prior reviews of this test's characteristics.

Not a "zero miss" test, but, depending on the pre-test likelihood based on other clinical factors, a very useful screening test.

"Re-evaluating the diagnostic accuracy of the tongue blade test: still useful as a screening tool for mandibular fractures?"
www.ncbi.nlm.nih.gov/pubmed/23490109

Quite bluntly, you're more likely to die.

These authors analyzed the 2008 Nationwide Emergency Department Sample, using 4,225,973 patient encounters as the basis of their observational analysis.  The absolute mortality differences between weekday emergency department presentations and weekend emergency department presentations is tiny – about 0.2% difference.  However, this difference is very consistent across type of insurance, teaching hospital status, and hospital funding source.

The NEDS sample did not offer these authors any specific explanation of the "weekend effect", but they expect it is due to decreased resource availability on weekends.  The authors note specific systems in place (e.g., trauma centers, PICU, stroke centers) where weekend staffing is unchanged have demonstrated the ability to eliminate such weekend phenomena.  However, it's probably never going to be the case that weekend shifts are less desirable – so we're probably stuck with this slight mortality bump on weekends.

"Don't get sick on the weekend: an evaluation of the weekend effect on mortality for

This article is an overview of the critical procedures performed over a one-year period at Cincinnati Children's, a large, well-respected, level 1 trauma center with a pediatric emergency medicine fellowship program.  In theory, this facility ought to provide trainees with top-flight training, including adequate exposure to critical life-saving procedures.

Not exactly.

In that one year period, the PEM fellows performed 32 intubations, 7 intraosseus line placements, 3 tube thoracostomies, and zero central line placements.  This accounted for approximately 25% of all available procedures – attending physicians and residents poached the remainder of procedures during the year.  Therefore, based on this observational data, these authors conclude the training in PEM might not be sufficient to provide adequate procedural expertise.  Then, the authors note pediatric emergency departments have such routinely low acuity – 2.5 out of every 1,000 patients requiring critical resuscitation – that it is inevitable these skills will deteriorate.

Essentially, this means the general level of emergency physician preparedness for a critically ill child is very low.  PEM folks might have more pediatric-specific experience – but very limited procedural exposure – while general emergency physicians perform procedures far more frequently – but on adults.  The authors even specifically note 63% of PEM faculty did not perform a single successful intubation throughout the entire year.

Their solution – which I tend to agree with – is the development of high-quality simulation tools to be used for training and maintenance of skills.  Otherwise, we won't be providing optimal care to the few critically ill children who do arrive.

"The Spectrum and Frequency of Critical Procedures Performed in a Pediatric Emergency Department: Implications of a Provider-Level View"
www.ncbi.nlm.nih.gov/pubmed/22841174

The Annals of Emergency Medicine Journal Club regarding IST-3 has been published as free fulltext online.  This article was written by myself, Yashwant Chathampally, and Gregory Press at The University of Texas Health Science Center at Houston.

It may be downloaded here:
"rt-PA and Stroke: Does IST-3 Make It All Clear or Muddy the Waters?"

Recent medical school graduates are familiar with the Step 2 Clinical Skills examination, a day-long charade of simulated clinical encounters intended to screen out medical students who are incapable of functioning in a clinical setting.  This test was adapted from the ECFMG Clinical Skills Assessment, intended essentially to screen out foreign medical graduates with inadequate communication skills to safely practice medicine in the United States.

However, U.S. and Canadian medical school graduates pass this test 98% of the time on the first attempt, and 91% of the time on a re-attempt.  This means each year $20.4 million are expended in test fees – and probably half again that amount in travel expenses – to identify 30-odd medical school graduates who are truly non-functional.  The authors of this brief letter in the NEJM suggest, with interest compounding secondary to medical school debt repayments, it costs over a million dollars per failed student.

Clearly, some medical students are not capable of functioning as physicians.  However, clinical skills teaching, evaluation, and remediation ought to be part of the purview of the medical school training program that has multi-year longitudinal experience with the student, not a one-day simulation.  I'm sure some of the few who fail Step 2 CS twice are capable of safely practicing medicine, and certainly many who pass Step 2 CS still require additional teaching.  I agree with these authors that this test is an expensive and ineffective farce.

Then again, as this NYTimes vignette points out, medical schools are having a tough time failing folks for poor clinical skills.  However, the solution is not to pass the buck along to the NBME.

"The Step 2 Clinical Skills Exam — A Poor Value Proposition"
www.nejm.org/doi/full/10.1056/NEJMp1213760

Featured today as a guest blog, revisiting the JAMA Clinical Evidence synopsis critiqued last month on this blog, here and here.

It's rather an experiment in discovering just how influential social media has become – open access, crowdsourced "peer review" – and whether this mechanism for addressing conflict-of-interest in the prominent medical journals is more effective than simply attempting a letter to the editor.

KevinMD.com – "The filtering of medical evidence has clearly failed"

Endotoxin mediated circulatory collapse remains a theoretical target in the treatment of sepsis.

But, eritoran won't be one of the agents used to ameliorate its effects.

After a phase II trial found sepsis patients randomized to eritoran had 37.5% mortality compared with 56.3% in the placebo group, the manufacturer sponsored a multi-national, multi-center phase III trial enrolling 1,951 patients.  And, in short – no mortality benefit overall, and no individual subgroups of severe sepsis with any indication of benefit.  The authors comments speak wistfully of the early favorable results before finally concluding: "Eritoran joins a long list of other experimental sepsis treatments that do not improve outcomes in clinical trials in these critically ill patients."

Interestingly, the study concluded in 2010 – meaning it took 2 1/2 years for the results to reach publication.  The reader will have to derive their own interpretation regarding whether this had anything to do with being negative results from a manufacturer-sponsored trial.

"Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis"

This entertaining brief communication refers to Chvostek sign – the twitching of the facial muscles after tapping the facial nerve purportedly associated with hypocalcemia.

This neurologist notes, after one of his residents presented with bilateral Chvostek sign, he convenience sampled other residents and medical students on the wards – and 6 out of 11 exhibited Chvostek sign.  He otherwise notes 25-43% of healthy individuals exhibit this sign and 29% of patients with hypocalcemia do not.  He bluntly states Chvostek sign should simply be retired as a clinically relevant entity.

Stick with the Trousseau sign!

"Chvostek sign, frequently found in healthy subjects, is not a useful clinical sign"
http://www.neurology.org/content/80/11/1067.full