ShortCuts-This Week in the Journals

March 10, 2008

rooseveltisland.jpgCommentary by Cara Litvin MD, Executive Editor, Clinical Correlations 

Vaccines were the buzz this week after it was made public that a federal government program designed to compensate people after vaccine injuries agreed to compensate the family of an autistic child, concluding that the vaccines may have “aggravated” an underlying mitochondrial disorder, leading to autism-like symptoms. The case drew new attention to a long standing controversy centering on the possible link between thimersol, a preservative previously used in childhood vaccines, and autism. However, many major studies have found no such link and the rates of autism have remained stable even after thimersol was removed from vaccines in 2001. Even Sen. John McCain added his two cents, citing “strong evidence” of a link between autism and thimersol in childhood vaccines at a recent town hall meeting.

In other vaccine news, reported in The Lancet this week were the results of a phase II trial of an Angiotensin II vaccine that appears to safely reduce blood pressure in mildly hypertensive patients. The vaccine contains a virus-like particle that stimulates antibody production to Angiotensin II. The half-life of the vaccine is about 4 months, making a simple injection three times a year a plausible future treatment for elevated blood pressure. Although the trial only involved a total of 72 patients, the prospect of an alternative to daily antihypertensive medication is quite exciting.

Published in the NEJM this week was a study examining how genetic variability may affect a person’s initial response to warfarin. The study focused on polymorphisms of genes encoding two proteins- CYP2C9, involved in the metabolism of warfarin, and VKORC1, which recycles reduced vitamin K and plays a role in the production of other clotting factors. When comparing two different haplotypes of VKORC1 (A/A vs. nonA/nonA), patients with the A/A haplotype appeared to reach a therapeutic level nearly twice as fast as the nonA/nonA haplotype. CYP2C9 was not a predictor of the time to first therapeutic INR but did predict time to supratherapeutic level. Although it’s easy to become confused with the genetic jargon, the study is significant because it opens the door to the possibilities of using pharmacogenetics in clinical practice. In a few years, genetic testing may not only take the guesswork out of coumadin dosing, but it may also usher in an entire new approach to prescribing medications based on using genetic variation to predict drug metabolism and response to therapy.

Of course, none of this pharmocogenetic stuff is relevant if placebos are just as effective as real medications. In a study published as a research letter in JAMA this week, healthy paid volunteers were given a placebo that they were told was a new opioid. They were then asked to rate their pain after receiving electrical shocks to the wrist. Half the participants were told that the placebo pain medication cost $2.50, while the other half were told that it had been discounted to $0.10. Those who received the purportedly more expensive placebo had significantly greater pain reduction than those who received the “discounted” placebo. The study substantiates the phenomenon of the placebo effect and also explains why direct to consumer marketing may be so powerful.