ShortCuts- This Week in the Journals

December 1, 2008

alaska-095.jpgCommentary by Sherley Abraham MD, PGY-3

Faculty Peer Reviewed 

Feeling fatigued? Don’t Google your symptoms. Instead, have the heart to go out for a walk. After all, it takes guts to build bone. Things must be looking up if cancer rates are going down, and some cancers may even spontaneously disappear! These are among the topics providing Thanksgiving food for thought in this week’s ShortCuts.

A little knowledge can be dangerous, or at least provoke unnecessary anxiety. The NY Times reports of a Microsoft study of its employees showing that people who do web searches on symptoms are often led to the worst possible diagnosis. These searches for self-diagnosis often prompt research into more serious, although rarer diseases, a phenomenon coined “Cyberchondria.” For example, a search into headaches gives a spectrum of results from brain tumor to caffeine withdrawal, which may cause users to fear the worst. The NY Times article suggests that better search engines are needed to provide more reliable information.

The study also gives us a reason to leave the computer and do another activity, such as exercise. Physical inactivity may be the missing link between depression and coronary disease, says the recent Heart and Soul Study published in JAMA. The San Francisco VA based study followed 1,017 outpatients with known CAD for up to eight years, measuring PHQ scores and following annual risks of cardiovascular events. Ten percent of those with depression had events, compared to 6.7 percent of those without depressive symptoms. After adjusting for various factors, particularly lack of exercise, the 31 percent increased risk was minimized and found to be insignificant.

Still looking at the heart of the matter, the NEJM reports a study examining the merits of 64-Row Coronary CT Angiography. In nine centers, 291 patients underwent CTA followed by the gold standard of conventional coronary angiography in order to test diagnostic accuracy. Obstructive CAD was defined by at least a 50% stenosis. The characteristics of CTA as a test to detect or rule out obstruction were calculated at 85% sensitivity and 90% specificity, with a postive and negative predictive value of 91% and 81$ respectively. Although similar in its ability to identify disease and candidates for revascularization, CTA is not accurate enough to replace conventional angiography altogether.  Despite this limitation and little proven benefit, CTA does receive Medicare reimbursement, an irony highlighted in a perspective article also in NEJM. Our fee-for-service system still promotes using expensive, newer technology rather than advocating for evidence-based medicine.

Now, before losing all faith in medicine, we turn our attention to brighter news. The National Cancer Institute has released a report stating there has been a steady decline in the incidence and mortality rates of certain common cancers, namely prostate and lung cancer in men, breast cancer in women, and colorectal cancer in both. The reason may be a combination of better lifestyle, screening, and treatment. Lung cancer incidence, although declining in men, has increased among women, an association linked to increased smoking. The report also suggests mortality rates from lung cancer have decreased in states with more tobacco policies and taxes.

A study published in the Archives of Internal Medicine suggests some breast cancers may spontaneously regress without any intervention. Using a unique situation in Norway, the study compared the women in two groups before and after the 1996 introduction of widespread screening through mammography. For every 100,000 women, there were 1,909 new cases of invasive breast cancer found in those screened regularly compared to 1,564 cases among those without regular screenings. Various factors, such as use of HRT or inherent flaws in mammography, were examined but could not account for the 22 percent more cancers in those screened regularly. This led to the theory that certain cancers may spontaneously regress. For years, we have accepted the risk of unnecessary biopsies for ultimately benign findings. Is there also a risk of unnecessary treatment? At this point, it would be impossible to predict the natural course of these screening-detected cancers.

Another surprising finding has been made, this time by a Cell journal article reporting a link between gut serotonin and bone formation, leading to possible implications for osteoporosis. The LRP5 gene was targeted because historically, inactivation causes the rare disease osteoporosis pseudoglioma, characterized by weak bones and blindness, whereas over- activation of the gene causes very dense bones. This gene inhibits gut synthesis of serotonin which adversely affects bone formation. Using an animal model, it was found that LRP5 inactivation decreases bone formation, but decreasing serotonin levels normalizes bone formation and mass. NY Times commentary reports leaders in osteoporosis are receiving the news with cautious enthusiasm because the work did not involve humans. Perhaps LRP5 is the true link between characters played by Bruce Willis and Samuel L. Jackson in the movie Unbreakable.

Also reported in the Lancet is a new medication for obesity in phase II trials. Tesofensine is a reuptake inhibitor of norepinephrine, dopamine, and serotonin. In this study, 203 obese Danish patients were randomized to receive varying dosages versus placebo with a primary outcome of percentage change in body weight. In the treatment group, there was a 5-10% greater weight loss than diet and placebo. Adverse effects were mainly GI and the lower doses did not increase blood pressure as was seen with Meridia a few years ago. This amount of weight loss is modest, but there would be large health benefits in areas of diabetes and cardiovascular disease. 

Moving on to what is available now, the FDA has approved a new pain medication. Tapentadol is an analgesic working through opioid and non-opioid receptors. As with other opioids, there are expected GI side effects, and the drug carries the risk of CNS or respiratory depression as well as the potential for abuse.

References
Markoff J. Microsoft Examines Causes of ‘Cyberchondria.’ NY Times. 2008 Nov 25. http://www.nytimes.com/2008/11/25/technology/internet/25symptoms.html
Whooley MA, et al. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA. 2008 Nov 26;300(20):2379-88.
Miller JM, et al. Diagnostic Performance of Coronary Angiography by 64-Row CT. N Engl J Med. 2008 Nov 27;359(22):2324-2336.
Redberg RF, Walsh J. Pay Now, Benefits May Follow — The Case of Cardiac Computed Tomographic Angiography. N Engl J Med. 2008 Nov 27;359(22):2309-2311.
Jemal A, et al. Annual Report to the Nation on the Status of Cancer, 1975-2005, Featuring Trends in Lung Cancer, Tobacco Use, and Tobacco Control. J Natl Cancer Inst. 2008 Nov 25. (Epub ahead of print)
Zahl PH, Mæhlen J, Welch HG. The Natural History of Invasive Breast Cancers Detected by Screening Mammography. Arch Intern Med. 2008 Nov 24;168(21):2311-2316.
Yadav VK, et al. LRP5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum. Cell. 2008 Nov 28;135:825-837.
Kolata G. Bone Finding May Point to Hope for Osteoporosis. NY Times. 2008 Nov 27. http://www.nytimes.com/2008/11/27/health/research/27bone.html
Astrup A, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. The Lancet. 2008 Nov 29;372(9653):1906-1913.
FDA Approves New Drug to Alleviate Moderate to Severe Pain. FDA News. 2008 Nov 24. http://www.fda.gov/bbs/topics/NEWS/2008/NEW01916.html

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