Wednesday, December 7, 2011

No More Excuses For Not Giving TPA

Rather than restrict TPA for acute ischemic stroke to the small cohort of patients identified by strict exclusion criteria in the few completed randomized trials, the current crusade is to continue to try and give it to more patients on the fringes of eligibility.

This article promotes giving TPA to patients with "minor or rapidly improving" strokes, because the lead author (sponsored by Genentech) sees this classification of patients is responsible for 50% of the documented reasons why patients were excluded from receiving TPA.  In fact, if patients with mild and improving strokes received TPA, it would immediately double the rate of TPA use - and provide potentially excellent outcomes at 90 days for the manufacturers.

They base their assertions on a retrospective, uncontrolled evaluation of the discharge disposition of patients in this "minor or rapidly improving" cohort - and observe that only 72% of patients in this group were discharged home.  In their mind, patients could do much better (as measured by disposition location) if they had received TPA - and their final conclusion is that this exclusion criteria should be further studied so that it may be revoked.

But, their conclusions are a preposterous farce conjured out of fictionalization of the data.  Considering the median age of their cohort was 72, 30% of whom had prior stroke/TIAs, 26% were diabetic, 76% were hypertensive, etc. - the sheer fact that only 28% went to rehab/SNF/died is probably rather good performance.  The authors also admit they had no information regarding the initial residence of this mostly elderly cohort and have no idea if the patients discharged to nursing facilities originally resided there.  Finally, the article additionally states "outcomes for patients with mild/rapidly improving stroke were better than for rtPA-treated patients with mild stroke (NIHSS score of 0 to 5) but worse for patients with a final diagnosis of TIA."

Yes, they compared this mild stroke cohort data to the mild stroke cohort data that received TPA, and all outcomes - adjusted and unadjusted for NIHSS - significantly favored the non-TPA cohort.

....so the obvious conclusion is to find a way to give more of them TPA.

Lunacy.  Another example of bad literature undermining trust in a probably efficacious treatment.

"Outcomes in Mild or Rapidly Improving Stroke Not Treated With Intravenous Recombinant Tissue-Type Plasminogen Activator"
www.ncbi.nlm.nih.gov/pubmed/21903949

Tuesday, December 6, 2011

It's Another Chest Pain Prediction Rule!

Yet again, the insanity of the race to a zero-miss culture funds another chest pain discharge prediction rule.  In fact, the most telling part of this paper is in the very end when they compare the chest pain admission rates of the Canadian hospitals in this article to the U.S. hospital - 18% and 20% in Canada compared to 96% in the U.S. (combined ED observation status and inpatient).  The difference in those numbers is insane - and I'm sure people could easily debate which is the preferred side of those numbers to be on.

In any event, the study is a prospective, observational data-gathering study of 64 variables related to the presentation of chest pain - some of which are objective and some of which are historical.  It's an interesting read - in part because the inter-observer kappa for a lot of the historical variables is so terrible they weren't even usable.  After collecting all their data, they did 30-day telephone follow-up or vital records review to evaluate the combined endpoint of death, myocardial infarction, or revascularization.

Via the magic of recursive partitioning, a patient without new EKG changes, a negative initial troponin, no history of CAD, atypical pain, and age less than 40 years separated out 7.1% of their study population that had zero 30-day outcomes.  Adding a second negative troponin six hours later for the 41-50 year group gives another 11.2% of patients that had zero outcomes.  So, a facility that admits 96% of their patients could potentially reduce admissions - but it might have less utility in Canada.

I'd rather see a two-hour second troponin than a six-hour one; it might reduce sensitivity, but it's wholly impractical to tie up a bed in the ED for 6 hours for a patient you want to send home.  And, like most of these articles, the combined endpoint of death, MI, and revascularization is irritating.  Considering there were twice as many revascularizations as myocardial infarctions, there really ought to be more granularity in these sorts of studies with regard to the actual coronary lesions identified rather than simply lumping them into a combined endpoint.

"Development of a Clinical Prediction Rule for 30-Day Cardiac Events in Emergency Department Patients With Chest Pain and Possible Acute Coronary Syndrome"
www.ncbi.nlm.nih.gov/pubmed/21885156

Sunday, December 4, 2011

Mistakes In Cardiac Arrest Cause Bad Outcomes

Not surprising, of course, but an interesting analysis of a large data set.

The authors pulled 108,636 in-hospital cardiac arrest cases out of the National Registry of Cardiopulmonary Resuscitation and evaluated them for "errors" - such as multiple intubation attempts, incorrect medication administration, delays in code team activation, etc.  After attempting to control for all the differences (of which there were many) in level of care and type of patient suffering cardiac arrest, they finally find that any documented error in resuscitation led to a 9.9% increase in adjusted hazard ratio for death in non-VF/pVT, and a 34.2% increase in VF/pVT patients.

Specifically, when they break out the different types of errors, essentially all the effect size was related to delays in medication administration for non-VF/pVT, and delays in medication and failure to defibrillate in VF/pVT.

"Impact of resuscitation system errors on survival from in-hospital cardiac arrest"
www.ncbi.nlm.nih.gov/pubmed/21963583

Saturday, December 3, 2011

Physician Profiteering From Self-Referral

Unfortunately, another distasteful – and likely more common than the authors estimate – assessment of the unethical behavior of physicians.

This is from JAMA.  It's a health-insurance carrier records review regarding differences in rate of ordering nuclear stress testing and stress echocardiography depending on the cardiologist financial conflict-of-interest.  Basically, they were asking the question – if the ordering cardiologist had a financial interest in the imaging performance and interpretation, would they order more tests?

Sadly, as you might imagine, the answer is yet.  If the physician billed technical and professional fees for the nuclear stress, the adjusted OR for ordering a nuclear stress was 2.3 compared to physicians who had no financial interests in the nuclear stress.  For stress echocardiography, the adjusted OR was 12.6.

I have no doubt the same sort of thing happens with neurologists who own their own MRI facilities, etc.  Money corrupts physicians just the same as any other human being.

"Association Between Physician Billing and Cardiac Stress Testing Patterns Following Coronary Revascularization"
jama.ama-assn.org/content/306/18/1993

Thursday, December 1, 2011

C1-Esterase Inhibitor Might Improve Some Sepsis Outcomes

...or it might not.  This is a tiny study using a very expensive medication that probably works only on a few patients, but it's interesting nonetheless.

As part of the inflammatory cascade, C1-esterase inhibitor (C1INH) modulates the coagulation cascade, impacts leukocyte activation, enhances bactericidal activity, and prevents endotoxin shock in sepsis models.  So, sounds like a good thing - let's give it to patients and see what happens!

This was an open-label, randomized, controlled study in Moscow and St. Petersburg with 62 ICU patients - 20 controls and 42 treatment patients - that met inclusion criteria.  There were, unfortunately, a lot of differences between the control group and the treatment group.  These differences included a lot more post-operative patients, much more pneumonia, and more on the ventilator, and probably favored the treatment group.  The mortality is way better for the treatment group - 12% dead versus 45% - but it's simply impossible to attribute all the effects to C1INH with all the other confounding differences.

That being said, this study is consistent the effects from other small studies.  Therefore, we will likely hear more about C1INH after larger, manufacturer-sponsored trials also undoubtedly find a way to spin positive results.

"C1-esterase inhibitor infusion increases survival rates for patients with sepsis"
www.ncbi.nlm.nih.gov/pubmed/22080632