Date: February 4th, 2019

Guest Skeptic: Dr. Jerome Hoffman is a Professor Emeritus of Medicine and Emergency Medicine, University of California, Los Angeles.

Dr. Hoffman has been a voice of reason for decades and taught a generation of physicians critical appraisal skills. This has been through various peer reviewed publications, doing Emergency Medicine Abstracts (EMA) audio program with Dr. Rick Bukata, teaching at the Emergency Medicine and Acute Care Course among other things.

There was a recent controversy on twitter and I thought Dr. Hoffman needed to join the conversation. Listen to the SGEM podcast to hear the many things we discussed.

The website TheNNT.com has been a good resource to find unbiased critical reviews of the literature. However, Dr. Hoffman did have some concerns about how the concept could be hijacked. It appears his concerns may have come true.

TheNNT updated their page on thrombolytics for acute ischemic stroke on January 11th, 2019. They changed the recommendation from RED (No Benefit) to GREEN (Benefits > Harms). This was very disturbing on multiple levels.

Controversy about thrombolytics and stroke is not new and has existed since at least 1995 with the publication of the NINDS trial. The SGEM has summarized the dozen major RCTs looking at the issue of thrombolytics for acute ischemic strokes (SGEM Xtra). Six trials showed no benefit. Four trials were stopped early due to harm or futility and two trials reported benefit. I do not claim thrombolysis does not work because that would shift the burden of proof. Rather, I state that I am skeptical.

We did not re-hash all the trials in our conversation but instead focused on a couple key publications like NINDS and IST-3. The SGEM did a Classic Episode on NINDS with Anand Swaminathan (SGEM#70). Dr. Hoffman has published a graphic re-analysis of NINDS (Annals EM 2009) and Sayer et al responded in print (Annals EM 2010).

The other major trial that we discussed was the IST-3 study which was covered on SGEM#29. Hoffman and Cooper provided commentary on some of the limitations of IST-3 (EMA 2012).

“using a score that is highly unreliable even when calculated by a neurologist performing an in-person neurologic evaluation. He then acknowledges that this problem was enormously exacerbated in IST-3 because the scoring was done by a layperson; to make matters even worse, this was a layperson who, like the patient himself, was unblinded to treatment group.” Hoffman and Cooper

Another issue we discussed was the outcome measure of mRS or in the case of IST-3, the Oxford Handicap Score (OHS) which is very similar to the mRS. Previous research has shown the mRS to have poor inter-rater reliability (Wilson et al Stroke 2005) and issues with validity (Zhao et al Cerebrovasc Dis 2010).

The methodology was changed in IST-3 when they did not reach...