Tissue, Not Time, for Stroke

The new AHA guidelines for the use of endovascular therapy in acute ischemic stroke broadly include any patient within six hours of symptom onset.  These criteria are based, mostly, on MR-CLEAN – in spite of the follow-up EXTEND-IA, ESCAPE, and SWIFT-PRIME showing the highest yield patients are clearly those with salvageable tissue.  Treatment beyond six hours, however, is still considered reasonable – and this cohort from DEFUSE-2 seems to indicate as such.

Based on 78 patients with target mismatch volume on MRI prior to endovascular therapy, they found: time doesn’t matter, only reperfusion.  The reperfusion outcomes for intervention under six hours are, grossly, no different than the outcomes for those greater than six hours.  And, this makes sense – salvageable tissue is salvageable:

Frankly, this is probably the paradigm for which we should ultimately be moving for all stroke treatment.  Time should not be a limiting factor – and, vice versa, should not be the sole indicating factor.  Dead brain simply can’t benefit from revascularization – no matter how quickly it is provided, regardless of time window.  The traditional “non-contrast head CT” is no longer adequate to provide optimal stroke care – CT angiography with perfusion calculations, or a rapid MRI protocol, should probably form the basis of modern stroke care moving forward.

“Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue”
http://www.ncbi.nlm.nih.gov/pubmed/26224727

Not So Fast on Race-Related Oligoanalgesia

This recent study regarding pain control received a lot of press, covered by both Reuters and NBC News.  The general gist of the breathless coverage seems to indict physicians for latent biases against treating African American children with opiates.

I’m not so certain.

This is a retrospective evaluation of a national Emergency Department database of seven years of ED visits for appendicitis, looking at pain control disparity between white children and minorities.  Pain management was documented in only 57% of children, 41% of which was opiates.  Children of African American descent received opiate medication only 12% of the time, leading to the authors’ observations of an apparent reluctance to treat this population with opiates.

But, I think the foundation of their analysis may be misleading.  The authors state: “The following covariates were included in our analyses to adjust for potential confounding: ethnicity, age, sex, insurance status, triage acuity level, pain score, geographic region, ED type, and survey year.”  However, I think these data need to be addressed at a within-hospital level, not as a pooled cohort.  African Americans have been previously shown to be over-represented at low-quality, safety-net hospitals – the sort of hospitals almost assuredly do a poor job of addressing and managing pain across all their patients.  Indeed, when other researchers have looked at racial disparities in care for acute myocardial infarction, performing within-hospital analyses dramatically altered their findings, with individual hospital inadequacies accounting for a greater effect than ethnicity.

The foundational issues in race-related difference in care may yet be present, but I do not believe to the magnitude these data reflect.  Rather than suggesting “there may be a higher threshold of pain score for administering analgesia to black patients with appendicitis,” these data probably reflect the underlying under-resourced care available to this population.  A tremendous and embarrassing problem, to be sure, but with a different approach needed for a solution.

“Racial Disparities in Pain Management of Children With Appendicitis in Emergency Departments”
http://archpedi.jamanetwork.com/article.aspx?articleid=2441797

It’s Time to Fix NIHSS

The purpose of the National Institute of Health Stroke Scale is to describe stroke severity.  Every point represents a deficit on exam, so, higher is worse – except it’s not that simple.

Every point on the scale is, unfortunately, clearly unequal.  Partial paralysis of the face is 2 points.  Profound hemi-inattention is also 2 points.  One of those patients – unless they’re Derek Zoolander – is not disabled.

This is a study, along with others in a similar vein, that translates that common sense directly into an indictment of the NIHSS as currently used.  These authors retrospectively evaluate six “profiles” of patients with discrete clinical manifestations of stroke, by basing their analysis on specific NIHSS item.  They use the NIHSS data from 6,843 patients in the SITS-MOST data, and, essentially, they find very different survival curves for patients with similar NIHSS when specifically categorized by clinical syndromes.

This leads to two main points:

  • We shouldn’t be using the NIHSS the way we’re used to using it.
  • The clinical variability of patients with similar NIHSS can vastly affect stroke trials with low sample sizes.

Time to fix the NIHSS!

“National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome”

Social Media & Medicine: It’s Great! No, it’s Worthless! Wait, What?

In the pattern of the old “Choose Your Own Adventure” novels, you can be for, or against, the Iran deal – or for, or against, the utility of social media in dissemination of medical knowledge and clinical practice.

In the far corner, the defending champion, the curmudgeons of the old guard, for whom the journals and textbooks hold primacy.  The American Academy of Neurology attempted to determine whether a “social media strategy” for dissemination of new clinical practice guidelines had any effect on patient or physician awareness.  They published new guidelines regarding alternative medicine therapies and multiple sclerosis through their traditional member e-mails and literature.  Then, they posted a podcast; a YouTube video; added Facebook, LinkedIn, and YouTube advertisting; and hosted a Twitter chat with Time magazine and others.  Based on survey responses, they were not able to measure any increased awareness of the guidelines resulting from their social media interventions.

Then, the challenger: Radiopedia.org.  This second study evaluates the online views of three articles concerning incidental thyroid nodules on CT and MRI.  Two of the articles were in the American Journal of Neuroradiology and the American Journal of Roentgenology, and the third was hosted on Radiopedia.org.  The Radiopedia blog – with some cross-polination and promotion by traditional means – received 32,675 page views, compared with 2,421 and 3,064 for the online journal publications, respectively.  This matches the anecdotal experience of many blogging physicians, that their online content exposure far exceeds that of their traditional publications.

What’s my takeaway?  Audience matters, content matters, and execution matters just as much as the medium.  When engaging an audience like those attending or presenting at, say, a conference entitled “Social Media and Critical Care”, digital scholarship may easily exceed the value of traditional vehicles.  Alternatively, for a topic as rockin’ as esoteric neurology guidelines, there might simply be a maximal ceiling of interested parties.

“The Impact of Social Media on Dissemination and Implementation of Clinical Practice Guidelines: A Longitudinal Observational Study.”
http://www.ncbi.nlm.nih.gov/pubmed/26272267

“Using Social Media to Share Your Radiology Research: How Effective Is a Blog Post?”
http://www.ncbi.nlm.nih.gov/pubmed/25959491

The Old Man and the Tamiflu

Winter is coming, and so is Tamiflu.  And, this year, we saw two meta-analyses regarding Tamiflu – the Roche puppet-sponsored analysis was pro-Tamiflu, and the non-sponsored analysis was anti-Tamiflu.  However, it should be made clear – anti-Tamiflu still agrees there’s still some small magnitude of effect that must be weighed against the side effects and cost.

The CDC has been repeatedly castigated regarding their continued zealotry regarding Tamiflu, despite the controversy surrounding its use.  The official statement contends their stance is based on more than just RCT data, including the whole of the observational data regarding its use.

And, so, they’ve gone and created some more junk observational data.

Through torturing the Influenza Hospital Surveillance Network (FluSurv-NET), these authors gathered three years of elderly patients hospitalized for influenza.  They extracted the date of influenza onset and the date of initiation for antivirals, and then examined these for a surrogate outcome for effectiveness: discharge to an extended-care facility.  They found, of course, that antiviral treatment was significantly associated with independent discharge, with an absolute unadjusted magnitude of effect of 4%.  However, they also found age, ethnicity, weight, chronic medical conditions, cardiovascular disease, neurologic disorders, influenza vaccination status, influenza virus type, time of illness onset to hospitalization, and surveillance site to be associated with outcomes – many with similar or larger absolute effect sizes.

So, the conclusions here are based on: the outputs of the statistical black box.  Given the degree of adjustments, and allocation and selection bias, there’s not much can be said here – except to make it into a HealthDay and ACEP daily news headline.  Unfortunately, the authors use these data to support early care and antiviral intervention.  This may be true, of course.  However, in the context of the current study, the suggestion ought not be to inform clinical practice – but, rather, to generate hypotheses for future trials, or to serve as surveillance safety for current practice.

That said, once the overall costs and potential morbidity of hospitalized influenza patients are taken into account, the additive penalty of Tamiflu administration is likely far less than even any small magnitude of benefit.

“Impact of prompt influenza antiviral treatment on extended care needs after influenza hospitalization among community-dwelling older adults”

The Battle for Age-Adjusted D-Dimer

Around these parts, we are fans of the age-adjusted D-dimer.  Jeff Kline proposes their use in his algorithm for the diagnosis of PE.  We embed decision-support in our EHR to encourage their use.  But, this new review from Annals of Emergency Medicine describes its test characteristics in the Kaiser Permanente population – and reports the age-adjusted D-dimer is not infallible.

These authors look retrospectively at 31,094 patients over 50, with a chest- or respiratory-related complaint, for whom a D-dimer was ordered.  14,434 of these patients had a D-dimer above the “customary” level of 500 ng/dL, and clinicians ordered 12,486 imaging studies to evaluate for PE.  Of these, 507 were diagnosed with PE.  This gives a 4.1% yield for CTPA – which, frankly, is disturbingly low – but another topic for another day.

The 500 ng/dL threshold was sensitive for 497 of the 507, while using an age-adjusted D-dimer would have reduced sensitivity to 471 of the 507.  Thus, using an age-adjusted D-dimer in this retrospective cohort may potentially have introduced an additional 26 missed PEs.  The savings, however, amount to 2,924 fewer CTPAs – or, roughly, 100 CTs per missed PE.

The contemporaneous Twitter response:

@EBMgoneWILD @ZackRepEM So age-adjusted D-dimer is dead? 26 misses to save $290K in costs = dead.

— Robert McNamara (@RobertMcNamar12) September 4, 2015

I don’t think so – but questions abound, many of which need be directly addressed by our specialty.  What is an acceptable miss rate for pulmonary embolism?  What is an acceptable miss rate of the pulmonary emboli in this age-adjusted range, just above our prior test threshold?  Does the net harm reduction from reduced testing outweigh the harms of missing those PEs?  Do those PEs convey the same level of morbidity or mortality if the diagnosis is missed or delayed?  How does the radiologic false-positive rate trend for PEs whose D-dimers are just over the test threshold?  And, finally – the age-adjusted D-dimer is not a static construct – would other age-adjustment formulas strike a better balance between sensitivity and specificity?

When all the questions are posed, I believe the summative value shows it reduces physiologic harms from testing, harms from healthcare costs, and harms from false-positives.  But, like everything we do, the age-adjusted D-dimer is still deserving of continued questioning and refinement.

“An Age-Adjusted D-dimer Threshold for Emergency Department Patients With Suspected Pulmonary Embolus: Accuracy and Clinical Implications.”
http://www.ncbi.nlm.nih.gov/pubmed/26320520

Soothing Songs and the CT Scanner

Yes, this is a trial of music therapy.  In the Emergency Department.  What fun!

This is a convenience sample of 62 children up to three years of age being referred for head CT after minor trauma, randomized to either soothing music or none.  Children were assessed for calmness by a visual analog scale of anxiety and a Modified Ramsay Sedation Scale before transport to CT.  Then, music was either present or absent while the child was being positioned on the scanner.  A second assessment of anxiety was then performed prior to CT.

The good news, as reported by the authors:

In conclusion, measured on a VAS, there was a significant decrease in agitation in children undergoing a head CT when children’s songs with integrated heart beat sounds were played before and during the procedure.

Unfortunately for their comparison, the control group was quite calm to start – with little room to improve – while the experimental group was fussier at baseline.  And, even though the CT introduced some agitation into the control group, nearly identical numbers of patients in each group successfully completed their imaging.  So, even though I think their intervention has value, the reliability of their conclusion is probably threatened by the chance baseline differences between groups.

But, it otherwise makes sense – and, it’s harmless, zero-cost intervention – so, why not?

“Randomized single-blinded clinical trial on effects of nursery songs for infants and young children’s anxiety before and during head computed tomography”
http://www.ncbi.nlm.nih.gov/pubmed/26314215

Valsalva 2.0

The Valsalva maneuver’s effectiveness for supraventricular tachycardia is, essentially, the reason adenosine exists.  With rates of non-pharmacologic cardioversion merely 5-20%, it’s not absent of value, but hardly reliable.

So, I appreciate these authors innovation in trialling a new, improved Valsalva maneuver.  The comparator in this study was the “traditional” maneuver, as applied via a forced exhalation of 40 mmHg for 15 seconds.  The “modified” maneuver was the same exhalation, but followed by immediately laying the patient supine and having a passive leg raise performed.

With 214 patients analyzed in the intention-to-treat population in a multi-center randomized trial, the success rate was, essentially: 43% vs. 17% in sinus rhythm one minute after Valsalva.  This boiled down to only 57% of patients in the modified Valsalva group ultimately requiring any pharmacologic therapy, compared with 80% of the traditional method.

I don’t see any particular reason to suspect the modified version would be more harmful than the otherwise safe traditional method, so there shouldn’t be any reason to avoid teaching and using this new alternative.  This may also be of more use to patients at home in preventing an Emergency Department visit in the first instance.

“Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)61485-4/abstract (oa)

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

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”