ShortCuts-This Week in the Journals

December 12, 2007

TimberlineCommentary By: Sean Cavanaugh, M.D. Associate Editor Clinical Correlations

Science magazine published the first practical application of the induced pluripotent stem (IPS) cells in a mouse model for sickle cell anemia. As was recently published, skin cells can be transformed into pluripotent cells by the insertion of genes Oct4, Sox2, Lif4 and c-Myc, known to act together as master regulators, to keep cells in an embryonic stem cell-like state. In this experiment, gene specific targeting of these cells corrected the sickle cell gene and the transplanted mice subsequently demonstrated the production of healthy red blood cells. And while this is an exciting early application of the recently described IPS technology that demonstrates IPS cells can be used similarly to the more ethically complicated embryonic stem cells, significant problems associated with using retroviruses to reprogram cells need to be resolved before this technology can be used in humans.

Another trial calls into question the almost routine use of antibiotics in patients with sinusitis. JAMA this week features the results of a non-industry sponsored trial of only 240 patients randomized into one of four groups (antibiotics vs placebo along with nasal steroids vs placebo) and no statistical difference between treatment groups was seen. The net result of previous trials, many of which used x-rays to support the diagnosis, led the Cochrane database to infer a slight treatment effect from the use of antibiotics in sinusitis. This trial distinguished itself by using a relatively tight clinical definition of rhinosinusitis, and as such may have more practicality than other trials published on the subject.

JAMA also published the 1 year follow-up results of the ACUITY trial. As reported: at 1 year, no statistically significant difference was found in rates of composite ischemia or mortality among patients with moderate- and high-risk acute coronary syndrome undergoing invasive treatment between patients treated with bivalirudin (2 groups: 1 with and 1 without heparin), and GPIIb/IIIa inhibitors combined with heparin. There was no statistically significant difference in the rates of composite ischemia between patients receiving routine upstream administration of GPIIb/IIIa inhibitors vs deferring their use for patients undergoing percutaneous coronary intervention. The REPLACE-2 and ACUITY trials established the use of bivalirudin monotherapy for the treatment of acute coronary syndromes undergoing early invasive therapy as equivalent to heparin and GPIIa/IIIb with less bleeding in the short term setting, and this analysis provides longer term data to support it’s comparable clinical efficacy. Now, it seems, it’s a matter of cost.

Baclofen – who knew? The Lancet published an intriguing article looking at the use of baclofen to help maintain abstinence from alcohol. 84 patients with alcoholic cirrhosis were randomized to a 12 week trial comparing baclofen to placebo as part of an abstinence counseling treatment program. 71% of the patients treated with baclofen achieved and maintained abstinence as compared to 29% of the patients receiving placebo. An absolute risk reduction of 42%! This is a little trial with a surprisingly big result – further tests are certainly warranted to validate a finding of this magnitude, but it is certainly eye-catching.

For those who want to brush up on the issue, The Annals of Internal Medicine is releasing an early on-line position paper accompanied by an editorial on universal access to medical care in the US. The position paper is a ranging review of healthcare in America, how it compares to healthcare in other countries, and some suggestions for focused change. As we are moving into election year it is an excellent and thought provoking piece and a great place to start for folks mystified by the topic.