Endovascular for Stroke – Even Better than the Evidence

What happens when you let Medtronic, et al, author an article on endovascular therapy in The Lancet:  exactly what you'd expect.

We are, in principle, fans of endovascular therapy for acute stroke as presented in the major trials: ESCAPE, EXTEND-IA, and SWIFT-PRIME.  These trials carefully selected eligible patients by use of advanced perfusion imaging and demonstrated high rates of revascularization.  Viable brain plus restored flow has face validity for improved outcomes.

However, these sponsored authors use the meta-analysis for its most nefarious purpose: to obfuscate the important subtleties and eligibility criteria of its included trials.  These authors pool the aforementioned trials, along with MR CLEAN and REVASCAT to provide the following conclusion:
“Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location.”(emphasis mine)
The authors also provide a staggering number-needed-to-treat for endovascular therapy of 2.6.

But, of course, this was written to shock and awe the lay press and general medicine community, rather than edify the astute clinician.  Their NNT is not based on the typical dichotomous cut-off used in stroke trials of mRS 0-1 or 0-2 – but rather the hopelessly flawed ordinal shift analysis.  As the decades turn, apparently, we have forgotten why this approach was frowned upon from the start: it is not appropriate to equate the outcome value difference between mRS 5 and 4 with the difference between mRS 3 and 2, and the limitations in inter-rater reliability in the mRS introduce a vast additional amount of measurement error.  Then, by burying any mention of the strict imaging criteria responsible for the bulk of benefit seen in these trials, they mislead the reader into considering this therapy appropriate for all-comers.

Is there any value to these data as presented?  A little.  There is hypothesis generating evidence that tPA prior to endovascular therapy provides no additive benefit.  There is also evidence that increasingly distal sites of occlusion may not benefit from intervention.

Unfortunately, the flaws in this article outweigh the few potentially usable insights.  This is just yet another piece of direct-to-physician marketing masquerading as scientific evidence.

“Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials”
https://www.ncbi.nlm.nih.gov/pubmed/26898852

How Many ED Visits are Truly Inappropriate?

I’ve seen quite a bit of feedback on social media regarding this research letter in JAMA Internal Medicine.

This study evaluated, using National Hospital Ambulatory Medical Care Survey data, the incidence of hospital admission stratified by triage Emergency Severity Index.  They analyzed 59,293 representative visits from the sample and found 7.5% of them, on a weighted basis, were categorized as “non-urgent” – an ESI level 5 or presumed equivalent.  The typical assumption regarding these non-urgent visits is they represent inappropriate Emergency Department utilization.  This study found, however:
“… a nontrivial proportion of ED visits that were deemed nonurgent arrived by ambulance, received diagnostic services, had procedures performed, and were admitted to the hospital, including to critical care units.”
There are always limitations regarding the NHAMCS data, particularly with missing and imputed data.  Based on this, I tend to feel these data lack face validity.  The weighted incidence of admission for non-urgent patients was 4.4% compared with 12.8% of urgent visits, while 0.7% of non-urgent visits were to critical care units compared with 1.3% of urgent visits.  I certainly do not see similar relative proportions of admission, and then to critical care, for level 5 patients in my multiple practice environments.

Regardless, the general implication made by these authors is probably reasonable, refuting usage of ESI triage level 5 to accurately represent inappropriate Emergency Department visits.  However, left equally unstated, is an acknowledgement that ESI also fails to accurately categorize urgent visits – which ties to the rhetoric of trying to conflate “non-urgent” as “inappropriate and “urgent” as “appropriate".

ESI, as currently implemented, will not be a reliable tool for directing patients to other sources of care – but, with some fuzziness, probably still gives a reasonable estimate of the overall burden of inappropriate ED visits for some policy applications.

“Urgent Care Needs Among Nonurgent Visits to the Emergency Department”
https://www.ncbi.nlm.nih.gov/pubmed/27089549

Try to Avoid tPA When Already Bleeding

Coming to us from the Department of Common Sense: don’t give tPA to stroke patients who already have intracranial hemorrhage.  There’s a little more subtlety here, of course, because in this instance, we’re dealing with cerebral microbleeds – tiny foci of angiographic damage visualized only on MRI.

These authors performed a pooled and individual-patient meta-analysis of those undergoing MRI prior to treatment with intravenous thrombolysis.  When stratified by CMB burden, arbitrarily divided into “none”, “1-10”, and “>10”, the obvious is … obvious: patients who are already bleeding are more likely to continue bleeding.  In the unadjusted raw numbers, patients with no CMB had a symptomatic intracranial hemorrhage rate of 4.3%, those with 1-10 CMB had 6.1%, and those with >10 had 40.0%.

There are many technical limitations inherent to the retrospective nature of their study, as well as likely other confounding variables – but, the basic gist: our current practice relying only on non-contrast CT likely misses an important safety indicator in the setting of tPA use.

“Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden”
https://www.ncbi.nlm.nih.gov/pubmed/27088650

Trauma is Still Trauma the Next Day

Acute closed head trauma is easy enough – and challenging enough.  There are validated decision instruments and guidelines, yet still plenty of CTs performed absent sound indications.  However, the question this study addresses is slightly different: what to do with those who present in a delayed fashion following minor head trauma?

The authors probably sum it up best in a reasonably concise fashion:
“Patients presenting after 24h of injury are a potentially distinct subpopulation. They could be at lower risk, as there is evidence that patients with mild/minor head injury who have injuries requiring neurosurgery will deteriorate within 24h. Alternatively, they could be a self-selecting higher-risk group attending due to the worsening or persistence of symptoms.”
These authors reviewed 2,240 patient encounters resulting in a CT scan of the head, with a goal of winnowing it down to just those performed for a traumatic indication.  Of those, 549 were performed within 24 hours of injury and 101 were delayed presentations.  There were 46 (8.4%) CTs positive for traumatic injury in the acute presentations and 10 (9.9%) in delayed, while 5 and 3 patients each underwent neurosurgical intervention, respectively.  So, the answer to their research question, at least in pragmatic terms, may be that the two forces balance each other out.

These authors also present “sensitivity” statistics regarding the utility of guidelines at predicting the presence of an important TBI, and quote a sensitivity of 70% based on chart review.  The denominator for sensitivity would more appropriately the entire population of presentations for trauma, not simply those who underwent CT scanning.  It is also probably more likely, given these patients had important TBI on CT, there may have been undocumented, guideline-compliant, indications not abstracted by chart review.

While our decision instruments for closed head injury were derived in typically an acute population, I would not yet draw any conclusions refuting their generalizability to delayed presentations.

“CT head imaging in patients with head injury who present after 24 h of injury: a retrospective cohort study”
https://www.ncbi.nlm.nih.gov/pubmed/27076439

The Unmagical Checklist

The checklist has reached ascendant status in medicine.  As introduced into the mainstream by Atul Gawande, they have begun to permeate every nook of healthcare delivery.  However, evidence of benefit when applied to one particular problem in one particular setting is no guarantee of universal utility.

These authors performed a study in Brazilian intensive care units, using a cluster-randomized pre/post design to evaluate the effect of a quality improvement effort built around a checklist.  Each element on the checklist represented a consensus or evidence-based practice associated with improvement in surrogate markers for patient outcomes.  The combined intervention was hoped to improve overall in-hospital mortality for ICU patients at the intervention hospitals.

It didn’t – mortality increased similarly for both intervention and control ICUs.

In fact, for all secondary clinical outcomes – catheter-related infections, ventilator-associated pneumonia, urinary tract infections, ICU days, etc. – there were no significant improvements over the baseline period, and no difference compared with controls.  There were small improvements in processes of care, such as VTE prophylaxis, catheter use, and appropriate tidal volumes during ventilation – but without corresponding clinical outcome improvement.

Interestingly, clinicians working in the intervention ICUs typically felt as though their ICUs were safer.  They were more likely, sometimes significantly so, to provide answers reflecting positive associations regarding their working conditions and safety climate.  Indeed, the intervention was perceived as so likely to be beneficial even prior to the start of the study that a short duration was mandated for the trial so all ICUs could eventually start using the checklist.

These authors have several justifications for why their checklist did not function appropriately, focusing on various details regarding the trial.  I think the simplest expression regarding the effectiveness of a checklist relates to the magnitude of effect and the baseline frequency of adherence.  Unless a significant magnitude of effect is seen by improving compliance with an intervention, and the intervention itself is infrequently performed, returns will diminish dramatically.  A checklist such as this, with multiple low-yield elements, is unlikely to return substantial patient-oriented outcome improvements.  Indeed, the resources devoted to checklist rounding and adherence may even dilute the focus on important clinical considerations.

“Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients”
https://www.ncbi.nlm.nih.gov/pubmed/25928627