ShortCuts- This Week in the Journals

September 22, 2008

alaska-031.jpgCommentary by Rachana Jani MD, PGY-2

This past week has been emotional to say the least. Fall has officially begun and the stock market continues to be in disarray. Nevertheless, the Wall Street Journal found time to focus on news other than the current state of our financial system.

The WSJ had brokers reading about denosumab, which may be a much needed jackpot drug for Amgen. The Journal of Bone and Mineral Research released the results from the FREEDOM trial, a Phase III study looking at the effects of denosumab on vertebral, nonvertebral and hip fractures. Denosumab, a human monoclonal antibody to RANKL, (ligand that activates osteoclast proliferation and differentiation) was found to have a statistically significant 68% reduction in vertebral fractures, 20% for nonvertebral fractures, and 40% for hip fractures, not to mention an increase in bone mineral density. This may pose some healthy competition for the bisphosphonates that were highlighted in this week’s updated ACP Clinical Practice Guidelines for the prevention and treatment of osteoporosis. It’s nice to know there are some things in life we can try to prevent.

On that note, I want to encourage you to look back at the happier times of the months past and consider the potential long-term investment you can make by continuing that healthy lifestyle the summer beckoned and the bikini demanded. The British Medical Journal published a prospective cohort study this week looking at middle-aged women and the relative risk of mortality regarding cigarette smoking, obesity, inactivity, poor diet, and alcohol consumption over a 24-year follow-up period. Relative risks of mortality of five versus zero lifestyle risk factors were 3.26 for cancer mortality, 8.17 for cardiovascular mortality, and 4.31 for all cause mortality. 28% of deaths were attributed to smoking and 55% to the combination of these poor lifestyle factors. With this, I hope I have convinced you that all the calorie counting and waist measuring you did during these sunny months was worth it and not to fall to the temptation of comfort food and hibernation as the cold sets in.

Diet was also a hot topic in the Journal of Respiratory and Critical Care Medicine this week. Researchers issued findings that sulfuraphane, an antioxidant found in broccoli, may lead to a reduction in the oxidative stress that is the key promoter of pathogenesis in COPD patients. In COPD, antioxidants play a critical role in mitigating the severity of disease and researchers found a decrease in lung function with reduced expression of these antioxidants, in particular nuclear factor erythroid 2-related factor 2 (NRF2)-dependant antioxidants. With sulfuraphane, there was a decrease in the degradation of anti-inflammatory antioxidants and NRF2. By restoring NRF2 function and subsequently alleviating oxidative stress, researchers hope the progression of COPD can be halted. Other foods rich in sulfuraphane include cabbage and brussel sprouts – maybe all these years Mom really was onto something.

While on the topic of COPD, I should mention a nested case-control study from the Annals this week looking at veterans with newly diagnosed COPD that reports one of the most commonly prescribed medications, ipratropium, may be harmful. This study found inhaled corticosteroids and long-acting beta-agonists were associated with decreased odds of death, OR .80 and .92 respectively, while ipratropium was associated with an increased risk, OR 1.11. Regarding cardiovascular death, ipratropium was associated with a 34% increase in the odds of cardiovascular death while inhaled corticosteroids showed a 20% decrease. Theophylline was also associated with an increase in respiratory deaths. Granted, more studies are warranted to further evaluate the risks associated with these common COPD medications – in the mean time however, COPDers may want to start eating their vegetables.

JAMA was also concerned with what we consumed this week – surprisingly not about what we were eating, but what our food was packaged in. In this cross-sectional analysis, Bisphenol A (BPA), a monomer found in polycarbonate plastics and epoxy resins was evaluated for its impact on chronic exposure in humans. The safety profile of BPA has been questioned for decades based on animal models showing neurogenic toxicity, developmental toxicity, and carcinogenic activity. As recently as 2007 did countries quell BPA fears stating the average levels in humans was not enough to cause harm. However, this study found that increases in urinary BPA concentration was associated with increased odds ratios for cardiovascular disease (CAD, MI, angina), 1.39, and diabetes, 1.39. There was also an association with increased liver enzyme abnormalities, particularly alkaline phosphatase, GGT, and LDH. In April of this year, Canada banned this chemical, yet our FDA still fails to take action. This definitely adds a whole new dimension to the paper versus plastic debate.

On a more positive note, the NY Times tried to bring some good news to the public from this week’s NEJM. Researchers from Mayo found that CT colonography was able to identify 90% of patients with large adenomas or cancers, as defined by 10mm or more. For adenomas 6mm or larger, the sensitivity was 78%. Does this mean CT colonography will be taking over and the hours spent convincing a patient to undergo colonoscopy are in the past? Not necessarily. Though insurance companies may be considering CT colonography as the cheaper alternative to screening, the Journal also pointed out the drawbacks of CT colonography, which included high rate of false negatives, extracolonic findings, inaccuracy of detecting flat growths, and the cumulative radiation exposure every 5 years, still making colonoscopy the preferred diagnostic tool. For now, at least, it seems some preventative ways of the past will remain the final word of the future.

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