Category: Neurology

HIAT-2 for Prognosticating Outcomes After Endovascular Interventions in Stroke: Proving Once Again Sick People are Sick

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Since the publication of IMS-3, SYNTHESIS and MR RESCUE in the NEJM earlier this year, proponents of endovascular interventions for acute ischemic stroke have hypothesized why these trials were universally negative. Among the various explanations, one of the most prominent was that the trial designs selected the wrong patients. In order to fully highlight the benefits of endovascular therapy it must be performed on large vessel occlusions with ischemic but viable brain tissue down stream. The authors of a recently published study in STROKE have suggested a solution for this very problem. With the publication of their derivation and validation cohorts of the second generation of the HIAT score, HIAT-2 score, they postulate this decision rule will help predict which patients will benefit from endovascular interventions. The second revision of the HIAT score incorporates the original 3 factors, age, NIHSS and blood glucose at presentation in addition to the ASPECT score of the initial non-contrast CT. As opposed to the initial iteration of HIAT (1 point allotted for each of the 3 factors), HIAT-2 is a 10-point scale (10 being most severe) with age, ASPECT score, NIHSS and blood glucose level relatively weighted in descending order of influence.

The score was retrospectively derived and validated from two prospectively gathered databases of patients who underwent endovascular treatment for acute ischemic stroke. Older patients, with increased NIHSS and more ischemic changes on their initial CT fared far worse than their younger less critically presenting counterparts. In patients with a HIAT-2 scores of 5 or greater, 80% had a mRS of >4 at 90 days. A HIAT-2 score of >7 resulted in 100% of patients having a mRS of >4 at 90 days. The authors conclude that since patients with a high HIAT-2 score had poor 90-day outcomes, endovascular interventions should be limited to patients with a HIAT-2 score of 5 or less.

Never mind that the HIAT-2 score is only moderately capable of identifying those with a poor outcome after endovascular intervention (AOC is only 0.73), the more egregious logical fallacy committed by these authors was to conclude that the HIAT-2 score will differentiate those who will benefit from an endovascular intervention from those who will not. HIAT-2 does nothing of the sort. It is merely a predictor of prognosis at 90 days. Older patients, with more severe strokes at presentation (both clinically and radiologically) will have a worse prognosis no matter what interventions are performed. Interestingly, if the HIAT-2 score is utilized as proposed by its authors, it would exclude the patients who were originally hypothesized to benefit from these endovascular interventions. Patients with symptoms severe enough (usually NIHSS 10 or greater) to be large vessel occlusions are the types of strokes, which lend themselves to endovascular interventions. These are the types of infarcts the HIAT-2 score would exclude from endovascular treatment options.

Finally, in the IMS-3 trial though the HIAT-2 score was not specifically measured, age, NIHSS and the ASPECT score were all recorded. 31% of the cohort was younger than 65, over half the cohort was ASPECT 8,9, or 10 and greater than 80% had a NIHSS at presentation of 19 or less. No benefit of endovascular treatment over tPA was seen in any of the subgroups that are the most heavily weighted components of the HIAT-2 score.

The HIAT-2 score would require prospective validation before it can be used clinically, but I argue that in its current form, HIAT-2 is unable to answer the question for which it was conceived. At present the best evidence we have demonstrates endovascular interventions are no better than tPA (and some would argue tPA is no better than placebo). More high quality trials are needed to identify if there is a subgroup of patients who may benefit from endovascular interventions but pseudoscience and logical fallacies do nothing to augment the knowledge we have gained so far.

“Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke”
www.ncbi.nlm.nih.gov/pubmed/23929748

HIAT-2 for Prognosticating Outcomes After Endovascular Interventions in Stroke: Proving Once Again Sick People are Sick

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Since the publication of IMS-3, SYNTHESIS and MR RESCUE in the NEJM earlier this year, proponents of endovascular interventions for acute ischemic stroke have hypothesized why these trials were universally negative. Among the various explanations, one of the most prominent was that the trial designs selected the wrong patients. In order to fully highlight the benefits of endovascular therapy it must be performed on large vessel occlusions with ischemic but viable brain tissue down stream. The authors of a recently published study in STROKE have suggested a solution for this very problem. With the publication of their derivation and validation cohorts of the second generation of the HIAT score, HIAT-2 score, they postulate this decision rule will help predict which patients will benefit from endovascular interventions. The second revision of the HIAT score incorporates the original 3 factors, age, NIHSS and blood glucose at presentation in addition to the ASPECT score of the initial non-contrast CT. As opposed to the initial iteration of HIAT (1 point allotted for each of the 3 factors), HIAT-2 is a 10-point scale (10 being most severe) with age, ASPECT score, NIHSS and blood glucose level relatively weighted in descending order of influence.

The score was retrospectively derived and validated from two prospectively gathered databases of patients who underwent endovascular treatment for acute ischemic stroke. Older patients, with increased NIHSS and more ischemic changes on their initial CT fared far worse than their younger less critically presenting counterparts. In patients with a HIAT-2 scores of 5 or greater, 80% had a mRS of >4 at 90 days. A HIAT-2 score of >7 resulted in 100% of patients having a mRS of >4 at 90 days. The authors conclude that since patients with a high HIAT-2 score had poor 90-day outcomes, endovascular interventions should be limited to patients with a HIAT-2 score of 5 or less.

Never mind that the HIAT-2 score is only moderately capable of identifying those with a poor outcome after endovascular intervention (AOC is only 0.73), the more egregious logical fallacy committed by these authors was to conclude that the HIAT-2 score will differentiate those who will benefit from an endovascular intervention from those who will not. HIAT-2 does nothing of the sort. It is merely a predictor of prognosis at 90 days. Older patients, with more severe strokes at presentation (both clinically and radiologically) will have a worse prognosis no matter what interventions are performed. Interestingly, if the HIAT-2 score is utilized as proposed by its authors, it would exclude the patients who were originally hypothesized to benefit from these endovascular interventions. Patients with symptoms severe enough (usually NIHSS 10 or greater) to be large vessel occlusions are the types of strokes, which lend themselves to endovascular interventions. These are the types of infarcts the HIAT-2 score would exclude from endovascular treatment options.

Finally, in the IMS-3 trial though the HIAT-2 score was not specifically measured, age, NIHSS and the ASPECT score were all recorded. 31% of the cohort was younger than 65, over half the cohort was ASPECT 8,9, or 10 and greater than 80% had a NIHSS at presentation of 19 or less. No benefit of endovascular treatment over tPA was seen in any of the subgroups that are the most heavily weighted components of the HIAT-2 score.

The HIAT-2 score would require prospective validation before it can be used clinically, but I argue that in its current form, HIAT-2 is unable to answer the question for which it was conceived. At present the best evidence we have demonstrates endovascular interventions are no better than tPA (and some would argue tPA is no better than placebo). More high quality trials are needed to identify if there is a subgroup of patients who may benefit from endovascular interventions but pseudoscience and logical fallacies do nothing to augment the knowledge we have gained so far.

“Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke”
www.ncbi.nlm.nih.gov/pubmed/23929748

HINTS vs. ABCD2 in Dizziness

Dizziness in the Emergency Department sends everyone down their favorite diagnostic algorithm, with outcomes ranging from utterly benign to impending permanent disability.  I’ve covered the repurposing of the ABCD2 score for risk-stratification in dizziness before, showing it had some utility in predicting posterior circulation stroke.

However, unsurprisingly, these authors demonstrate examination maneuvers specifically targeted at evaluating cerebellar function outperform risk-stratification.  The HINTS (head impulse, nystagmus type, test of skew) evaluation compared with the ABCD2 (age, blood pressure, clinical features, duration, diabetes) in a convenience sample of 190 prospectively collected patients with acute vestibular syndrome.  Of these 190 patients, 124 had a central cause for their vertigo (stroke, hemorrhage, space-occupying lesion).  The sensitivity and specificity of the ABCD2 score in predicting a central lesion was 58.1% and 60.6%, respectively, while the HINTS score resulted in 96.8% and 98.5%, respectively.

It’s a bit of a straw-man comparison – considering the ABCD2 score was never designed to detect posterior circulation stroke, only to affect probability estimates for cerebrovascular disease.  The prevalence of disease in this sample probably also leads to an overestimation of the specificity of the HINTS exam, but it has otherwise been found to have very good test characteristics.

Visit EMCrit for more information and video footage of the HINTS test, if you’re not already using it.

“HINTS Outperforms ABCD2 to Screen for Stroke in Acute Continuous Vertigo and Dizziness”
http://www.ncbi.nlm.nih.gov/pubmed/24127701

tPA for TIA?!

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last year, the debate over the use of alteplase in acute ischemic stroke has continued to heat up. The issue really boiled over in June after BMJ reporter Jeanne Lenzer wrote a scathing evaluation of clinical guidelines after the publication of the new ACEP Clinical Policy on the use of alteplase in ischemic stroke. Now, to muddy the waters further, enter the discussion of giving alteplase to transient ischemic attacks (TIAs).

That’s right, this week, the American Journal of Emergency Medicine published a case report discussing the administration of alteplase to a patient that the treating physicians agreed had a TIA. Before we get into the article itself, let’s take a stroll back in time to 1995.

On December 14th, 1995, the NEJM published the NINDS trial and ushered in the era of alteplase for acute ischemic stroke. One of the major exclusions in the study, and one that few have argued with, was “rapidly improving or minor symptoms.” In essence, NINDS sought to exclude patients with TIAs. The reason for this is elegantly stated by Dr. David Liebeskind (UCLA Stroke Center):

“Thrombolysis is not a rational or evidence-based therapeutic option for transient ischemia irrespective of vascular status . . . The prevailing obsession with arterial occlusion has erroneously focused attention on clots rather than ischemia . . . Imaging of occlusion without consideration of clinical details or pahtophysiolgical mechanisms may therefore be misleading.” (Stroke 2010).

From a pathophysiological and outcome standpoint, there is no good reason to administer alteplase to a patient with a TIA regardless of imaging. If the patient has an NIHSS of 0, there is no room for improvement, only harm.

In spite of this, the authors of the above case report recount the story of a 37-year-old woman who presented with a TIA. Her presenting NIHSS was 0. CT angiogram showed a “near total occlusion of the M2 segment of the MCA.” There is no report about the presence of an ischemic penumbra.  After the CTA was completed, the patients’ symptoms returned but then rapidly resolved. At this point, the physicians decided to administer alteplase in spite of the absence of symptoms. She was then transferred to a stroke center for consideration of neurointerventional care (a therapy proven not to work. See NEJM March 2013). Interestingly, the authors base their decision to treat on imaging findings but never discuss the resolution of these findings after therapy (i.e. no mention of repeat CTA or MRI/MRA).

What does this tell us about alteplase for TIA? Not much. This is a case report and gives us no information about causality of treatment. It doesn’t even show efficacy of concept because pathophysiologically the idea of giving alteplase to a TIA doesn’t make sense.  The authors talk about weighing risks and benefits outside of standard indications and contraindications. But what they have done is give a potentially dangerous, life-threatening medication to a patient with no disability at the time of administration. They have taken on all the risk of the drug without any potential benefit.

What this report really shows is the concept of “indication creep.” Earlier this year, the TREAT task force recommended that patients with rapidly resolving symptoms (but some continued deficit) should be considered for thrombolytic treatment (Stroke 2013). This recommendation wasn’t based on any literature but rather an expert consensus from a meeting sponsored by Genentech (Boehringer-Ingelheim in Europe). This case report is simply the logical extension of an illogical idea: if thrombolytics should be given to a patient with rapidly resolving symptoms, why not give it to one with no symptoms but imaging abnormalities?

The authors conclude by pointing the finger at EM physicians stating that we, “have been historically slow in adopting thrombolytic therapy for CVA.” We haven’t embraced this treatment because we don’t see definitive evidence that it works and we do see the potential harms. A month ago at ACEP, a group of EPs voted 75% to 25% to reconsider the ACEP clinical policy on tPA. The authors go on to suggest that this patient did well and required no further treatments because she received “off-label” thrombolytics. This link violates everything we know about research. Just because something happens after you do something, doesn’t mean the thing you did caused the outcome. Domhnall Brannigan told a wonderful story during his lecture at SMACC last year about a patient who presented with stroke-like symptoms and nausea. Dr. Brannigan gave the patient ondansetron for the nausea and minutes later the patient had resolution of his symptoms. None of us, though, are rushing to give ondansetron for ischemic CVA. The proposition by these authors is just as ludicrous.

“TPA for TIA: The case for “off-label” use of thrombolytics.”
http://www.ajemjournal.com/article/S0735-6757(13)00747-X/fulltext

References
Sobel RM, Wu DT, Hester K, Anda K. tPA for TIA: The case for “off-label” use of thrombolytics. Am J EM 2013; 06 November 2013 (10.1016/j.ajem.2013.10.046

The National Institute of Neurological Disorders and Stroke, rt-PA Stroke Study Group. Tissue Plasminogen Activator for Acute Ischemic Stroke. NEJM 1995; 333(24): 1581-7.

Liebskind DS. No-Go to tPA for TIA. Stroke 2010; 41(12): 3005-6.

The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force. Levine SR, Khatri P, Broderick JP, Grotta JC et al. Review, historical context, and clarifications fo the NINDS rt-PA stroke trials exclusion criteria: part 1: rapidly improving stroke symptoms. Stroke 2013; 44: 2500-2505

tPA for TIA?!

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last year, the debate over the use of alteplase in acute ischemic stroke has continued to heat up. The issue really boiled over in June after BMJ reporter Jeanne Lenzer wrote a scathing evaluation of clinical guidelines after the publication of the new ACEP Clinical Policy on the use of alteplase in ischemic stroke. Now, to muddy the waters further, enter the discussion of giving alteplase to transient ischemic attacks (TIAs).

That’s right, this week, the American Journal of Emergency Medicine published a case report discussing the administration of alteplase to a patient that the treating physicians agreed had a TIA. Before we get into the article itself, let’s take a stroll back in time to 1995.

On December 14th, 1995, the NEJM published the NINDS trial and ushered in the era of alteplase for acute ischemic stroke. One of the major exclusions in the study, and one that few have argued with, was “rapidly improving or minor symptoms.” In essence, NINDS sought to exclude patients with TIAs. The reason for this is elegantly stated by Dr. David Liebeskind (UCLA Stroke Center):

“Thrombolysis is not a rational or evidence-based therapeutic option for transient ischemia irrespective of vascular status . . . The prevailing obsession with arterial occlusion has erroneously focused attention on clots rather than ischemia . . . Imaging of occlusion without consideration of clinical details or pahtophysiolgical mechanisms may therefore be misleading.” (Stroke 2010).

From a pathophysiological and outcome standpoint, there is no good reason to administer alteplase to a patient with a TIA regardless of imaging. If the patient has an NIHSS of 0, there is no room for improvement, only harm.

In spite of this, the authors of the above case report recount the story of a 37-year-old woman who presented with a TIA. Her presenting NIHSS was 0. CT angiogram showed a “near total occlusion of the M2 segment of the MCA.” There is no report about the presence of an ischemic penumbra.  After the CTA was completed, the patients’ symptoms returned but then rapidly resolved. At this point, the physicians decided to administer alteplase in spite of the absence of symptoms. She was then transferred to a stroke center for consideration of neurointerventional care (a therapy proven not to work. See NEJM March 2013). Interestingly, the authors base their decision to treat on imaging findings but never discuss the resolution of these findings after therapy (i.e. no mention of repeat CTA or MRI/MRA).

What does this tell us about alteplase for TIA? Not much. This is a case report and gives us no information about causality of treatment. It doesn’t even show efficacy of concept because pathophysiologically the idea of giving alteplase to a TIA doesn’t make sense.  The authors talk about weighing risks and benefits outside of standard indications and contraindications. But what they have done is give a potentially dangerous, life-threatening medication to a patient with no disability at the time of administration. They have taken on all the risk of the drug without any potential benefit.

What this report really shows is the concept of “indication creep.” Earlier this year, the TREAT task force recommended that patients with rapidly resolving symptoms (but some continued deficit) should be considered for thrombolytic treatment (Stroke 2013). This recommendation wasn’t based on any literature but rather an expert consensus from a meeting sponsored by Genentech (Boehringer-Ingelheim in Europe). This case report is simply the logical extension of an illogical idea: if thrombolytics should be given to a patient with rapidly resolving symptoms, why not give it to one with no symptoms but imaging abnormalities?

The authors conclude by pointing the finger at EM physicians stating that we, “have been historically slow in adopting thrombolytic therapy for CVA.” We haven’t embraced this treatment because we don’t see definitive evidence that it works and we do see the potential harms. A month ago at ACEP, a group of EPs voted 75% to 25% to reconsider the ACEP clinical policy on tPA. The authors go on to suggest that this patient did well and required no further treatments because she received “off-label” thrombolytics. This link violates everything we know about research. Just because something happens after you do something, doesn’t mean the thing you did caused the outcome. Domhnall Brannigan told a wonderful story during his lecture at SMACC last year about a patient who presented with stroke-like symptoms and nausea. Dr. Brannigan gave the patient ondansetron for the nausea and minutes later the patient had resolution of his symptoms. None of us, though, are rushing to give ondansetron for ischemic CVA. The proposition by these authors is just as ludicrous.

“TPA for TIA: The case for “off-label” use of thrombolytics.”
http://www.ajemjournal.com/article/S0735-6757(13)00747-X/fulltext

References
Sobel RM, Wu DT, Hester K, Anda K. tPA for TIA: The case for “off-label” use of thrombolytics. Am J EM 2013; 06 November 2013 (10.1016/j.ajem.2013.10.046

The National Institute of Neurological Disorders and Stroke, rt-PA Stroke Study Group. Tissue Plasminogen Activator for Acute Ischemic Stroke. NEJM 1995; 333(24): 1581-7.

Liebskind DS. No-Go to tPA for TIA. Stroke 2010; 41(12): 3005-6.

The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force. Levine SR, Khatri P, Broderick JP, Grotta JC et al. Review, historical context, and clarifications fo the NINDS rt-PA stroke trials exclusion criteria: part 1: rapidly improving stroke symptoms. Stroke 2013; 44: 2500-2505

Intracranial Angioplasty, Where Did We Go Wrong?

This week The Lancet published a friendly reminder from the SAMMPRIS investigators warning us that it is a bad idea to go putting stents in places they do not belong. This unintended favor came in the form of the publication of the long term follow-up from the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis trial online this week in The Lancet.

The SAMMPRIS trial, originally published in the NEJM in 2011 applied the frequently  attempted, but rarely accurate mantra,“If it works on the heart then it should work on the brain.” The authors took high risk TIA patients with radiologically confirmed intracranial stenosis and randomized them to “aggressive” medical management or percutaneous transluminal angioplasty and stenting (PTAS). The trial was stopped early because of the exorbitant amount of periprocedural strokes and death among those in the PTAS group. Specifically there was an 8.9% absolute increase in stroke and 1.8% increase in mortality within the first 30 days of enrollment. The authors’ summary of this dramatic failure was that the true benefits and harms could not be assessed at the time of initial publication, as there was not enough data to determine if the long term benefits outweighed these initial harms.

The recent paper is the 2-year follow up of this cohort and specifically addresses these presumed “long term benefits”. The overall occurrence of stroke was 19% in the medically managed group vs 26% in the PTAS group. It is apparent no clinically significant benefit exists especially when considering the devastating early harms. Yet another example of our limited understanding of the pathophysiology of atherosclerotic disease, and the ramifications of introducing thrombogenic objects into already tight spaces.

“Aggressive Medical Treatment With or Without Stenting in High-Risk Patients with Intracranial Artery Stenosis (SAMMPRIS): the Final Results of a Randomized Trial” http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62038-3/fulltext

Nihilism, Emergency Medicine, and the art of doing nothing at emnerd.com and @CaptainBasilEM

Intracranial Angioplasty, Where Did We Go Wrong?

This week The Lancet published a friendly reminder from the SAMMPRIS investigators warning us that it is a bad idea to go putting stents in places they do not belong. This unintended favor came in the form of the publication of the long term follow-up from the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis trial online this week in The Lancet.

The SAMMPRIS trial, originally published in the NEJM in 2011 applied the frequently  attempted, but rarely accurate mantra,“If it works on the heart then it should work on the brain.” The authors took high risk TIA patients with radiologically confirmed intracranial stenosis and randomized them to “aggressive” medical management or percutaneous transluminal angioplasty and stenting (PTAS). The trial was stopped early because of the exorbitant amount of periprocedural strokes and death among those in the PTAS group. Specifically there was an 8.9% absolute increase in stroke and 1.8% increase in mortality within the first 30 days of enrollment. The authors’ summary of this dramatic failure was that the true benefits and harms could not be assessed at the time of initial publication, as there was not enough data to determine if the long term benefits outweighed these initial harms.

The recent paper is the 2-year follow up of this cohort and specifically addresses these presumed “long term benefits”. The overall occurrence of stroke was 19% in the medically managed group vs 26% in the PTAS group. It is apparent no clinically significant benefit exists especially when considering the devastating early harms. Yet another example of our limited understanding of the pathophysiology of atherosclerotic disease, and the ramifications of introducing thrombogenic objects into already tight spaces.

“Aggressive Medical Treatment With or Without Stenting in High-Risk Patients with Intracranial Artery Stenosis (SAMMPRIS): the Final Results of a Randomized Trial” http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62038-3/fulltext

Nihilism, Emergency Medicine, and the art of doing nothing at emnerd.com and @CaptainBasilEM

The “Ottawa SAH Rule”

This is a rather dangerous article for many reasons.  Firstly, it’s published in a high-impact journal and received a fair bit of coverage in the news media.  Secondly, it concludes its discussion by suggesting this ought to be adopted as a standardized rule for the evaluation of acute headache – this isn’t just a descriptive study on features of subarachnoid hemorrhage, it’s been given an official-sounding title, the “Ottawa SAH Rule”.  Because of this, there’s significant potential for the rule described here to be adopted as widespread practice.

Therefore – it better be nearly perfect.

This is a prospective cohort from 10 university-affiliated Canadian hospitals.  They looked at non-traumatic headaches reaching maximal intensity within 1 hour not part of a recurrent headache syndrome, and found 132 patients with SAH out of 2,131 assessed.  They specifically gathered information on three previously-derived prediction rules and found none of them were 100% sensitive – so they chose the required elements from each to reach 100% (95% CI 97.2-100) sensitivity.  The cost of this 100% sensitivity?  Degeneration of specificity from the 28-35% in the three individual rules down to 15% (95% CI 13.8-16.9) in the final rule.  The authors observed application of the derived rule would have decreased investigations for SAH from 84% of the enrolled cohort down to 74% of the enrolled cohort, and thusly their rule is superior to routine clinical practice by maintaining 100% sensitivity while decreasing resource utilization.

I think their inclusion criteria are fine – a rapid-onset, severe, atraumatic headache is the classical population of interest.  Patients without this feature have such a low incidence of SAH that it’s unreasonable to evaluate for it.  Their outcome measures, unfortunately, were a little softer.  The positive diagnoses are reasonable – CT proven SAH or positive lumbar puncture with a source feature on cerebral angiography.  However, only 82% underwent CT and 39% underwent LP, with a six month telephone follow-up – and a small number were lost to follow-up.  Many would argue that CT alone is not sufficient for ruling out SAH, and 6-month survival is a limited proxy.  This weakens its claim for 100% sensitivity.

Then, of course, a 15% specificity is awful.  This isn’t necessarily a criticism of the authors, but more a recognition of the limitation of distilling diverse clinical data into concise decision instruments.  19 different patient features were significantly different between the SAH and no-SAH groups; reducing this to just 6 features discards so much information that an instrument designed for a complex clinical prediction is bound to fail.  There were 1,694 false positives by the rule compared with 132 true positives.  If this rule is applied without the strict exclusion criteria specified in the publication, there may be a huge number of inappropriate investigations.

Then, the rate of investigation comparison is also probably invalid.  These institutions underwent specific 1-hour orientation to the study being performed and were actively involved in gathering clinical data for the study.  I’m certain the 84% rate of investigation observed was conflated by the ongoing research at hand.  The previous Perry study from 2011 had an evaluation rate of 57%, so it’s hard for me to believe the statistics from the current publication.

Finally, the kappa values for inter-observer agreement were rather mixed.  Based on only sixty cases where two physicians evaluated the same patient, four of the six final rule elements had kappas between 0.44 and 0.59, representing only moderate agreement.  This is a significant threat to the internal validity of the underlying data in support of their rule.

Overall, yes – the elements they identify through their observational cohort are likely to capture most cases of SAH.  However, the limitations of this study and the poor specificity make me reluctant to buy in completely – and certainly not adopt it as a standardized “rule”.

“Clinical Decision Rules to Rule Out Subarachnoid Hemorrhage for Acute Headache”
http://www.ncbi.nlm.nih.gov/pubmed/24065011

ACEP/AAN Guideline Writers Respond

Some of the authors of the new ACEP/AAN clinical policy have responded to the BMJ report discussing conflict-of-interest in guidelines, focusing on the science behind the tPA portion.

If you haven’t already visited, it’s truly a star-studded sort of discussion, with David Newman, Jerome Hoffman, Robert Solomon, Jeffrey Saver, Stephen Messe, Peter Sandercock, and James Grotta, among others.

Most Positive LPs Aren’t SAH

There’s still active debate regarding whether CTs are now sensitive enough to pick up all subarachnoid hemorrhage, and whether lumbar puncture is about to go the way of the dodo.  Their argument is based on the premise that, despite the imperfect gold standard of this practice changing study, very few negative CTs result in positive lumbar punctures.

However, as this chart review study shows, in real-world practice, most positive LPs may in fact be false positives.  This is a 10 year review at Barnes Jewish Hospital, where they were able to identify 57 patients with negative CT and positive LP, who subsequently underwent angiography for diagnostic confirmation.  Of these, three patients had positive findings – only two of which were ultimately determined to be true positives.

This is a little different than previous reviews, in which 53% of negative CT/positive LP represented true positives.  These authors suggest the previous higher-yield results are likely the result of dependence on xanthrochromia as part of the diagnostic evaluation, and a cohort with a longer duration of symptoms prior to LP.

The truth is likely somewhere in the middle, splitting the difference between useless and half-wrong.  This probably aids the “CT, no LP” camp – of which I tend towards – by demonstrating the preponderance of false positives inherent to LP for SAH.

“Yield of Cather Angiography After Computed Tomography Negative, Lumbar Puncture Positive Subarachnoid Hemorrhage”
www.ncbi.nlm.nih.gov/pubmed/23619131‎