Friday, July 20, 2012

Empiric Measurement of Bias in Unblinded Trials

This lovely article was passed along to me by David Newman during a discussion of IST-3 – the recently infamous, massive randomized trial of thrombolysis for acute stroke.  There are two ways of thinking about IST-3, and how the results are viewed in the literature seems to depend how much funding you receive from Boehringer or Genentech.  The first way of thinking seems to be accept the results as published, pick apart the subgroups, do statistical contortions, and then either come out in the "pro" camp (Boehringer) or the "con" camp.


The second way of thinking, supported by this article, is "garbage-in, garbage-out".  The key issue for this approach is that IST-3 is an unblinded, open trial, which introduces bias - treating clinicians and patients who believe TPA is a "promising, yet unproven" treatment (from the uncertainty principle of the study) are perceived as more likely to contribute to favorable reported outcomes when receiving the experimental intervention.  This effect is probably even more pronounced given that much of the follow-up scoring for the Oxford Handicap Scale was performed by mail-in questionnaire, rather than standardized expert evaluation – which has rather poor kappa to begin with.


Page three of this article delves into the empiric analysis of the impact of blinding, and the relative likelihood of unblinded trials to report favorable outcomes.  Essentially, the relative chance of reporting both favorable and unfavorable outcomes are significantly affected.  In clinical terms, this leads to presentation of results in which the benefits are exaggerated and the harms are minimized.  In the context of IST-3, this essentially means the likelihood of any hidden positive effects vanishes, while the poor outcomes are underreported – and it's more "negative" than "neutral".


The authors also note they are preparing a systematic review of trials with blind and non-blind outcome assessors, which would be particularly apt to IST-3, as well.


"Blinding in Randomized Clinical Trials: Imposed Impartiality"
http://www.ncbi.nlm.nih.gov/pubmed/21993424

Wednesday, July 18, 2012

Keeping Children Happy

When I started in medicine – hardly long ago – Child Life, if it existed at all in the Emergency Department, might have consisted of a few plastic toys and perhaps a Nintendo Entertainment System.  Now, the staple of every department is an iPad, filled with apps and distractions for children.

This is a short article from the Pediatric literature reviewing a few cases in which tablet computers proved useful, along with a review of several apps worth loading on for distraction during potentially troubling procedures.  Most of the apps reviewed are for iPad, but equivalent exist for Android devices and iPhone.



I've definitely gotten mileage out of the movie "Toy Story 3" on my iPhone – perfect for the 3 AM laceration repair when Child Life has gone home for the night.

"Using a Tablet Computer During Pediatric Procedures - 
A Case Series and Review of the 'Apps'"

Monday, July 16, 2012

Massive Overtesting for Febrile Seizures

Frightening, yet benign, febrile seizures are seen frequently in the Emergency Department.  The American Academy of Pediatrics recommends minimal evaluation for uncomplicated febrile seizures, and invasive testing only in complex cases or those with other indications for testing.

Despite this, the real-world experience documented by these authors at a community hospital in New York is slightly different.  Rather than minimal testing, 100% of patients - mostly aged greater than 12 months - received a CBC and Chem7.  94% received a blood culture, 94% received a urine culture, and 85% had a chest x-ray.  24% had CSF cultures and 21% had CT scans - mostly the complex febrile seizures.

The yield of all this testing - they diagnosed a few UTIs, and one blood culture grew out salmonella.  The authors appropriately feel this testing strategy is excessively wasteful - and confirms the AAP recommendations.

"Current Role of the Laboratory Investigation and Source of the Fever in the Diagnostic Approach"
http://www.ncbi.nlm.nih.gov/pubmed/22653461