What did you learn in school today?

Prof. Dr. Peter A. Rinck.In my leisurely hours of continuing education in February and March, I read some articles in the daily papers and learned journals that taught me new aspects of medicine. Among them were the following issues. We learned in medical school that high cholesterol (i.e., LDL cholesterol) will kill you. We have to lower it. Now we hear with increasing intensity that LDL cholesterol may not be the cause of atherosclerosis and coronary heart disease. It must be something else, and the question is what. Recent evidence boosts the conclusion that statins, drugs used to lower cholesterol production, restore and improve endothelial function directly. Medical teaching that cholesterol plays a key role in heart disease is open to question. Although scientific publications suggested for quite a while that cholesterol might not be the responsible foe, the public health dogma was never touched. Among the many agents sold to lower cholesterol are two drugs, ezetimibe and simvastatin, that operate on different mechanisms. When one of the major pharmacological players in the field combined them into a single medicament, the researchers found that cholesterol was lowered more than with one drug alone. The combination did not, however, accelerate the slowdown of fatty plaque accumulation in the arteries. I was curious and went a long way to get the physician's prescribing information of the medicament where one reads: "No incremental benefit of [the combination medicament] on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established."

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What did we learn? Back to the drawing board.Next topic: For decades I have followed the debate over diagnosis and treatment of prostate cancer: Operation is best. Radiation is best. Seeds are best. Hormones will heal you. It always depended on the eye of the medical beholder. Fifteen years ago, substantial controversy existed about the advisability and effectiveness of screening programs, the most appropriate staging evaluation, and the optimal management of patients with all stages of prostate cancer. There were inherent ambiguities in recommending staging and treatment choices.

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Some weeks ago, the U.S. Agency for Healthcare Research and Quality issued a review of prostate cancer treatments, including surgical removal, radiation, hormone therapy, and "watch and wait," which involves careful monitoring but no active treatment until the cancer shows signs of growing.Because none of these treatments emerged as superior, the agency came to the troubling conclusion that it could not recommend one over the others.

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What do you tell people who come to you, although you're are only a radiologist, and ask what treatment you would propose or consider? What did we learn? Back to square one. If now you get depressed and want to get happy again with Prozac, the antidepressant taken by some 40 million people worldwide, it will be cheaper for you to take a placebo or a glass of wine. Using the Freedom of Information Act, Irving Kirsch from the University of Hull and colleagues in the U.S. and Canada could access all clinical data submitted by the drug producer to the FDA. Apparently, some studies had not reached the public.

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The authors summarized their results: Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. In understandable words, there is hardly any difference between placebo and medicament. Such abrupt revelations are major changes for diagnostics and treatment entrenched for decades. What did we learn? We should ask ourselves: What comes afterwards? How do we react to developments like these? Of course, things like these never happen in radiology - at least, nobody talks about it. What did we learn? Always looks on the bright side of life.Let's see what we learn at this year's ECR.

REFERENCES

1. Merck/Schering-Plough Pharmaceuticals. Vytorin prescribing information. January 2008.
2. Garnick MB. Prostate cancer: screening, diagnosis, and management. Ann Intern Med 1993;118:804-818.
3. Wilt TJ, MacDonald R, Rutks I, et al. Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med 2008 Feb 4 [Epub ahead of print].
4. Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008 Feb;5(2):e45.