Friday, August 28, 2015

Endovascular Sans tPA in Bern

The first hints of a rollback in tPA use are starting to emerge – not unexpectedly, from those working to improve the outcomes of their endovascular programs.

This is a retrospective evaluation of patients from Bern, Switzerland, all treated with endovascular therapy.  Their registry includes 372 patients since 2004, all treated for MCA or ICA occlusions and with DWI measurements pre-treatment.  As with any data dredge, any findings are just hypotheticals – but, there’s a couple interesting tidbits:
  • Smaller lesions did much, much better – 54.5% achieved mRS 0-2 if lesion volume was <70mL, compared with 21.2% with lesion volume >70mL.
  • If you failed to reperfuse a lesion volume >70mL, mRS 0-2 outcomes sank to 8.6%.
  • Symptomatic intracranial hemorrhage jumped to 19.7% for lesion volume >70mL.
  • There were only 66 patients over >70mL lesion volume, but the best outcomes?  The 19 with mechanical therapy only – balancing 21.1% mRS 0-2 with only 5.3% SICH.
The authors ultimately conclude endovascular therapy for large lesion volumes might be best without any thrombolytic involved.

Wasn’t it lovely how fashionable tPA was – until endovascular therapy finally reached a tipping point in terms of efficacy?

“Younger Stroke Patients With Large Pretreatment Diffusion-Weighted Imaging Lesions May Benefit From Endovascular Treatment”
http://stroke.ahajournals.org/content/early/2015/08/06/STROKEAHA.115.010250.short

Wednesday, August 26, 2015

Clinicians or Statistics for Pediatric Abdominal Injury

PECARN is a wonderful thing.  Any individual pediatric facility sees a handful of children.  A handful, however, multiplied by 20, becomes potentially practice-changing.

And, this is an article further exploring the PECARN pediatric abdominal trauma prediction instrument, comparing its utility to typical clinician judgment.  As part of the initial derivation study, the surveyors asked each clinician to rate the likelihood of intra-abdominal injury, stratified <1%, 1-5%, 6-10%, 11-50%, or >50%.  Turns out, clinician judgement wasn’t too bad.

  • Of 9,252 children with <1% chance of injury requiring intervention, 35 (0.4%) had injuries identified.
  • Of 1,793 between 1-5% chance, 40 (2.2%).
  • Of 506 between 6-10% chance, 33 (6.5%).
  • Of 281 between 11-50% chance, 59 (21.0%).
  • Of 81 greater 50% chance, 36 (41.4%).

The problem with these data?  5,318 CTs were performed to identify 203 significant injuries, including 3,016 in those with <1% chance.

The prediction rule was both better and worse.  It was more sensitive than clinician judgment, but also less specific.  For an endeavor attempting to decrease CT utilization in children, it’s still not quite clear where this fits in – and whether using it in a fashion similar to PERC or D-dimer wouldn’t necessarily increase imaging.  It may, as these authors discuss, have more value in Emergency Departments without the same level of comfort managing traumatically injured children, as it may yet in face reduce imaging in that context.

“Comparison of Clinician Suspicion Versus a Clinical Prediction Rule in Identifying Children at Risk for Intra-abdominal Injuries After Blunt Torso Trauma”

Monday, August 24, 2015

Risk Stratification Cage Match & The Return of TIMI

Sending home chest pain has completely jumped the shark from frankly illegal to fashionably vogue.  Every day, another stick is shaken, and a mess of monkeys and new studies evaluating discharge strategies fall from the trees.

Today in the Octagon, five “established” risk scores for patients with acute coronary syndrome are pitted against each other in a prospective, observational study in Britain:  TIMI, GRACE, HEART, the Vancouver Chest Pain Rule (sure, OK), and the modified Goldman (???).  Each of these risk scores were paired with non-ischemic EKGs, and single initial blood samples for high-sensitivity troponin T (14 ng/L) and high-sensitivity troponin I (26.2 ng/L).  The authors’ stated goal: a negative predictive value of 99.5% for myocardial infarction within 30 days, and a capability of discharging at least 30% of patients at the initial presentation.

Oddly, it’s unexpectedly difficult to pick a winner.  The decision instrument with the greatest ability to discharge patients was TIMI ≤1, over 50% home from the ED, but it just barely missed the NPV threshold.  The modified Goldman ≤1, when paired with the troponin T, was capable of discharging 39.8% of patients with a sensitivity of 98.7%.  Then, the HEART score ≤3 was the most clinically acceptable when used with the troponin I assay, as it was the only decision-instrument taking into account small variations in serum troponin.  However, it just failed to meet the authors' NPV threshold, as well.

So, what has changed since we last crowned HEART the new gnat’s pajamas?  Mostly the troponin assays, although this study also focuses more on NPV than sensitivity.  Indeed, a single hs-cTnT <14 ng/L had an NPV of 98.3% in this study, regardless of all other clinical features.  The implication, potentially, may be that the ideal risk-stratification decision-instrument can be designed for greater specificity, rather than sensitivity.  Other methods to increase sensitivity, such as paired troponins in certain situations, may allow for even further decision-instrument specificity, depending, of course, on the acceptable miss rate.

Despite its performance here, I’m not advocating for a return to TIMI – or to the modified Goldman – because I’m not quite so keen on their sensibility in the ED.  However, the interaction of HEART with different assays is intriguing, and perhaps a venue for further investigation and refinement.  It's probably also worth mentioning an additional overlooked aspect – it is still OK to discharge a patient with a higher risk of AMI or death within 30 days if there is no additive survival benefit associated with acute hospitalization.

“Identifying Patients Suitable for Discharge After a Single-Presentation High-Sensitivity Troponin Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays”
http://www.ncbi.nlm.nih.gov/pubmed/26260100

Friday, August 21, 2015

Your CTPA is Lies

There are a few moments you pat yourself on the back in Emergency Medicine.  The good save.  Shared decision-making that goes well.  And, the small victory when you've utilized an evidence-based pathway for pulmonary embolism, and received positive results for the leviathan of over-utilization and over-diagnosis: the CT pulmonary angiogram.

Well, it’s time to deduct about 1.25 fingers from that pat on the back you give yourself, because, unfortunately, radiology PE overcalls may be more rampant than initially thought.

This is a retrospective, single-center study reviewing a year’s worth of CTPA for pulmonary embolism, a total of 937 studies.  Of the studies included, 174 (18.6%) were initially read as positive.  Then, each positive study was reviewed by a panel of three, specially trained chest radiologists, with their consensus read used as the gold standard for diagnosis.  And so: 45 (25.9%) were subsequently judged to be incorrectly read by the original radiologist – a quarter of positive studies! – with those patients almost certainly consigned to at least short-term anticoagulation as a result.

In a light moment in the discussion, the authors helpfully contribute the following commentary:
Furthermore, many pulmonary CTA examinations in our institution are ordered by the emergency department before assessment by the admitting medical team.
My heart goes out to the poor Scottish EM physicians, for whom their radiology colleagues apparently have quite the low opinion for appropriate testing.  However, the authors' attention may be better spent further discussing their own false-positive rate, which is double the ~11% rate of other similar reviews.  They also do not provide any accompanying data on the rate of false-negatives, although, in theory, these should be less clinically important.

So, think twice about doing your little happy dance for a positive CT – if your pretest likelihood was low, and the PE is subsegmental, there’s a substantial chance the stars have aligned in just the wrong constellation.

“Overdiagnosis of Pulmonary Embolism by Pulmonary CT Angiography”
http://www.ncbi.nlm.nih.gov/pubmed/26204274

Wednesday, August 19, 2015

EMLitOfNote Hits the Road

On hiatus and back to Houston!

Grand Rounds at the University of Texas Medical School at Houston:
"Life at Kaiser: Essays from the Future of Medicine" and a 2015 literature update.

and the keynote of the Texas EMIG Colloquium:
"There's Poison in the Well:  Why the Medicine You'll Practice is Wrong"

Can't wait to see everyone again!

Monday, August 17, 2015

Better Less than More for tPA

Ah, but this is not one of those rants about the inefficacy of tPA.  This is just an amuse-bouche of a mention of an article from Stroke, regarding a line of investigation in Asian countries.

In these countries, particularly Korea and Japan, there is some substantial thought given to “low dose” tPA being just as effective, with a lower risk of intracranial hemorrhage.  Interestingly, approximately 40% of acute stroke patients in Asian countries is at this lower dose, 0.6 mg/kg compared with the typical 0.9 mg/kg.  This study is a retrospective evaluation of registry data from 13 academic stroke centers, comparing 3-month outcomes on the modified Rankin Scale.

There were, essentially, two entertaining bits from this article:
  • The rate of symptomatic ICH in centers contributing at least 100 patients during the study period ranges from 3.7% on the low side up to 13.0% on the high.
  • Given the constraints of the study, they were unable to demonstrate any reliable difference between the two doses.  In fact, as you can see from the figure below, retrospective data can be adjusted, propensity matched, or essentially tortured to show whatever advantage preferred:

Should we be using low-dose?  And why stop at 0.6 mg/kg – why not 0.3 mg/kg?  And, further down the rabbit hole, back to the ideal dose of … none.  Ah, but I kid, I kid ….

“Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study”
http://www.ncbi.nlm.nih.gov/pubmed/26243232

Friday, August 14, 2015

Beaten Into Submission By Wrong-Patient Alerts

It’s a classic line: “Doctor, did you mean to order Geodon for room 12?  They’re here for urinary issues.”

And, the rolling of eyes, the harried return to the electronic health record – to cancel an order, re-order on the correct patient, and return to the business at hand.

Unfortunately, the human checks in the system don’t always catch these wrong-patient errors, leading to potential serious harms.  As such, this handful of folks decided to test an intervention intended to reduce wrong-patient orders: a built-in system delay.  For every order, a confirmation screen is generated with contextual patient information.  The innovation in this case, is the alert cannot be dismissed until a 2.5 second timer completes.  The theory being, this extra, mandatory wait time will give the ordering clinician a chance to realize their error and cancel out.

Based on a before-and-after design, and observation of 3,457,342 electronic orders across 5 EDs, implementation of this confirmation screen reduced apparent wrong-patient orders from approximately 2 per 1,000 orders to 1.5 per 1,000.  With an average of 30 order-entry sessions per 12-hour shift in these EDs, this patient verification alert had a measured average impact of a mere 2.1 minutes of time.

Which doesn’t sound like much – until it accumulates across all EDs and patient encounters, and, in just the 4 month study period, this system occupied 562 hours of extra time.  This works out to 70 days of extra physician time in these five EDs.  As Robert Wears then beautifully estimates in his editorial, if this alert were implemented nationwide, it would result in 900,000 additional hours of physician time per year – just staring numbly at an alert to verify the correct patient.

It is fairly clear this demonstration is a suboptimal solution to the problem.  While this alert certainly reduces wrong-patient orders of a measurable magnitude, the number of adverse events avoided is much, much smaller.  However, in the absence of an ideal solution, such alternatives as this tend to take root.  As you imagine and experience the various alerts creeping into the system from every angle, it seems inevitably clear:  we will ultimately spend our entire day just negotiating with the EHR, with zero time remaining for clinical care.

“Intercepting Wrong-Patient Orders in a Computerized Provider Order Entry System”
http://www.ncbi.nlm.nih.gov/pubmed/25534652

“‘Just a Few Seconds of Your Time.’ at Least 130 Million Times a Year”
http://www.ncbi.nlm.nih.gov/pubmed/25724623

Wednesday, August 12, 2015

The MD/NP Equivalency Study!

As covered by Medscape:
“Nurse practitioners’ diagnostic reasoning abilities compared favourably to those of doctors in terms of diagnoses made, problems identified and action plans proposed from a complex case scenario.”

Certainly not delving into the myriad of issues associated with healthcare roles and training, but, from a critical appraisal standpoint:

  • A gold standard for acute clinical evaluation determined by a general practioner, a rheumatologist, and a diabetes nurse practitioner.
  • An inability to recruit 30 physicians to match the 30 NPs for the study, and thus it proceeded with only 16.
  • Many of the “correct diagnoses” involved in their test of equivalency were related to chronic health maintenance, and not the acute illness of presentation.
  • The NPs recruited having had almost 30 years of clinical experience, compared with the physicians all still in training, with an average 6 years of experience, several of whom were engaged non-primary care (e.g., cardiology) specialties.

The commentary on Medscape waxes poetic regarding  reconciliation of independence and oversight issues based on this “evidence”.  The limitations in these data are so profound that this study is virtually meaningless – and serves no function in further illuminating the safety or effectiveness of scope of practice, as these authors unfortunately attempt.

“Nurse practitioners versus doctors diagnostic reasoning in a complex case presentation to an acute tertiary hospital: A comparative study”
http://www.ncbi.nlm.nih.gov/pubmed/25234268

Monday, August 10, 2015

Retinal Photography to Diagnose TIAs?

Our diagnostic approach to suspected cerebrovascular disease is quite simple.  Concerning neurologic findings or history?  Magnetic resonance imaging.

However, this approach is grossly inefficient – and, thus, the rise of various clinical scores such as the ABCD2 variants.  And, now, ocular fundus photography.  It generally makes sense – the retinal vessels travel through the optic nerve sheath.  They are, then, a unique window into the cerebrovascular circulation – and, accordingly, the degenerative diseases within.

It sort of works.

Looking at patients presenting to the ED with a report of focal neurologic deficits, the multivariate regression OR for cerebrovascular disease in patients with arterial narrowing in 2 segments is reported as 8.1 for stroke and 5.1 for TIA.  However, this finding was only present in 4 of 22 (18%) stroke patients and 6 of 59 (10%) TIA patients – compared with 5 of 176 (3%) patients who did not receive a diagnosis of cerebrovascular disease.

So, yes – it is probably true, as the authors claim, that finding arterial focal narrowing in the retinal vessels increases the likelihood of cerebrovascular disease (stroke and TIA).  But, clearly, the positive predictive value is still quite low, and the number of patients for whom this ocular photography adds substantially to the diagnosis is quite small.  At ~$25,000 a pop for the camera system, and the need for a specialist to screen the images for abnormalities, I do not share these authors’ enthusiasm for its eventual adoption into clinical practice.

“Ocular fundus photography of patients with focal neurologic deficits in an emergency department”
http://www.ncbi.nlm.nih.gov/pubmed/26109710

Friday, August 7, 2015

Gestational Age and D-Dimer Levels

In general, the utility of D-dimer for the evaluation of venous thromboembolism declines with gestational age.  The typical cut-offs for the 95th percentile, depending on your assay, become less and less relevant as pregnancy progresses.  Wouldn’t it be nice, perhaps, if we had reliable data?

So, well, here's something:

One glaring hole in this data is the broad inclusion criteria of “healthy” women.  No testing was specifically performed to exclude asymptomatic venous thromboembolism, so the possibility exists of inclusion of small, subsegmental pulmonary emboli, or of non-occlusive lower extremity deep venous thrombosis.  The effect on this data would be to increase the 95% percentile, and to widen the 95th percentile confidence interval.

Jeff Kline has proposed gradually increasing cut-offs of 750, 1000, and 1250 ng/mL for the first, second, and third trimester, respectively (based on a standard cut-off of 500 ng/mL).  This sample is much larger than the one cited by Kline in his “PE in pregnancy” algorithm, but his appear to be reasonable, sensitive cut-offs.  By far, the most important aspect of evaluating pulmonary embolism in pregnancy is simply to communicate the uncertainty, and to inform and share decision-making with the patient along the way.

“Gestation-specific D-dimer reference ranges: a cross-sectional study”
http://www.ncbi.nlm.nih.gov/pubmed/24828148