ShortCuts-This Week in the Journals

November 17, 2008

railroad.jpgCommentary by Paul Fenyves MD, PGY-3

Faculty Peer Reviewed 

General and Abdominal Adiposity and Risk of Death in Europe
More fat, Mortality: Published in the New England Journal of Medicine, a prospective, observational study of more than 300,000 Europeans, has found that, after adjusting for BMI, increasing waist circumference is associated with increasing risk of death. Men in the highest quintile of waist circumference (≥102.7 cm) had a 2.05 relative risk of death. Similarly, women in the highest quintile of waist circumference (≥89.0 cm) had a 1.78 relative risk of death. In both men and women, risk of death was related to BMI in a J-shaped manner – risk of death is increased in both very large and very small BMI’s. Interestingly, risk of death was lowest for men with a BMI of 25.3, which is generally considered to be slightly overweight. The study suggests that waist circumference should be used in conjunction with BMI to assess patient’s health.

Vitamins E and C in the Prevention of Cardiovascular Disease in Men
CV prevention is not E-C: Also from the Journal of the American Medical Association, a randomized, placebo-controlled, double-blinded study of almost 15,000 U.S. male physicians failed to show a reduction in cardiovascular events with either vitamin E or vitamin C supplements. Each participant was randomized to receive either 400 UI of vitamin E every other day or placebo, and either 500 mg of vitamin C daily or placebo. During a mean follow-up of eight years, the CV event rate was the same across all groups. Vitamin E, however, was associated with an increased risk of hemorrhagic stroke (HR 1.74).

Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes
Is ASA DOA for DM2?: A randomized, open-label trial in the Journal of the American Medical Association assessed the utility of aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus. The trial randomized 2539 Japanese diabetics to either low-dose aspirin (81mg or 100mg) or no aspirin and followed the participants for a median of 4.37 years. Although atherosclerotic events were lower in the aspirin group (13.6 VS 17.0 per 1000 person-years), the results were not statistically significant. However, the validity of the study was undermined by an overall event rate that was lower than anticipated, rendering the study underpowered. Furthermore, the applicability of the study to U.S. is unclear, since Japan has a relatively high incidence of stroke, but a relatively low incidence of coronary heart disease.

Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial
Another failed HIV vaccine: The Lancet released disappointing news from a trial of an HIV vaccine developed by Merck. Previous attempts to develop a traditional antibody-based vaccine for HIV have all proven fruitless. Efforts have since turned to the development of a vaccine to trigger cell-mediated immunity to HIV. Researchers hoped that such a vaccine would either confer immunity to HIV, or at least provide resistance to the virus – allowing the body to hold the virus in check in the event of an infection. The Step Study randomized 3000 HIV-1 negative individuals to receive either three injections of MRKAd5 HIV-1 gag/pol/nef vaccine or placebo. The trial was halted early at the first interim analysis, because a pre-specified futility boundary was met – the vaccine neither prevented HIV infection, nor reduced the viral load in HIV-infected patients.

A Doctor, a Mutation and a Potential Cure for AIDS
Two birds killed with one stone: The Wall Street Journal reported on the case of a patient in Germany who appears to be cured of AIDS by a stem-cell transplant. The patient, a 42 year-old American living in Berlin, suffered from both AIDS and leukemia. When the leukemia failed to respond to first-line chemotherapy, hematologist Dr. Gero Hütter recommended an allogenic stem-cell transplant. In addition to seeking an HLA-compatible donor, Dr. Hütter looked for donor who was CCR5-negative – the mutation which confers HIV-resistance to 1% of Europeans. After finding a suitable donor, a transplant was performed two years ago. Since that time, the patient has had no detectable HIV particles, despite not taking antiretrovirals. Obviously, this method could not be applied on a large scale as an HIV-cure: allogenic stem-cell transplants are expensive, suitable donors are not always available, and the mortality of the procedure is on the order of 30%. Nevertheless, the case lends credence to an on-going project in the U.S., which is attempting to develop an HIV therapy based on engineering CCR-5 mutations in HIV-infected patients.

Google Uses Searches to Track Flu’s Spread
Floogle: Google has released a new tool which may help track the spread of influenza across the United States. The tool, called Google Flu Trends (, uses flu-related search terms to predict the current incidence of influenza in a particular region of the country. The premise is that, as people become infected, they search the internet for information about the flu. For example, as flu cases increase in Detroit, more people in that area will google terms such as “runny nose” and “muscle ache.” At first glance, this approach seems to lack specificity, since symptoms of influenza are shared by many other URI’s. However, Google has validated their method using data from last year’s flu season – the predictions made using search terms from 2007 closely matched the influenza incidence as reported by the CDC for that year. Furthermore, Google reports that their data anticipated CDC reports by seven to ten days, suggesting that Google’s tool can be used to provide more timely information about the spread of influenza.