Archive for December, 2007

A Math Story for Professionals

Sunday, December 30th, 2007

Once upon a time in Futureland when TV celebrity and talk shows, sports events, and sitcoms were hemorrhaging viewers, giant sponsored colloquia were held to discuss various philosophical issues. These were broadcast on world wide television in 75 languages and viewed by 1.3-2.4 billion people every other night. One such seminar originating on a Swiss mountaintop dealt with a vexing international question: “What are two plus two?” Present were important world class experts from diverse disciplines.

When first asked, “What is the sum of two plus two?” the mathematician quickly answered, “four.”

Next in turn was the physicist who replied, “in the neighborhood of four.”

The engineer responded with, “four point zero, zero, zero plus or minus zero.”

The economist without hesitation concluded, “two plus two are seven.”

Next was the lawyer’s turn. He looked at the host and asked, “Could you repeat the question?” After it was again posed, the lawyer pondered a moment, shrugged his shoulders, and inquired, “What would you like?”

Finally, it was the physician’s opportunity. He slowly repeated the question over and over again. Finally his eyes brightened, he smiled and announced, “Let’s order some tests.”

Happy and Disease-Free New Years to All.

More Anti-Cholesterol News: Statins, Zetia, and Vytorin

Saturday, December 29th, 2007

Between 2000 and 2003 Merck and Shering-Plough conducted eight long-term studies on the safety of Zetia-statin combinations. Five have so far been unreported, but showed “possible liver side effects from Vytorin.” Two of the three studies reported showed safety problems, 19% of 433 patients in one series (Vytorin-Zocor and Zetia). 8% of 432 patients on Zetia and Lipitor in another series showing liver or gall bladder problems. Where are you, Dr. Jarvik?

Officials at the drug companies admit there is no present evidence that taking these drug combos, e.g. Vytorin, will reduce heart attacks or strokes. Yet they are betting on a 10,000 patient clinical trial to be finished in 2011 to support the hypothesis that Zetia will prove effective.

According to the New York Times, when the FDA approved Zetia in 2002, it relied on trials involving only 3,900 patients lasting no more than 3 months. “In those trials, 11 times as many people who took Zetia along with a statin subsequently had serious health problems…” These were mostly liver function abnormalities…”compared with those who took a statin alone.”

In the U.S., virtually all widely advertised drugs on TV as well as many unadvertised, carry warnings about the potential for liver damage and dangers for pregnant women, among other risks. The very omnipresence of these warnings convey a widespread sense of trust in drug promotion. After all, the manufacturers must be trustworthy, and so must be the regulators, otherwise they wouldn’t be admitting risks by taking their product.

Statins Plus:Troubling News about Zetia and Vytorin

Wednesday, December 26th, 2007

Tens of millions of people use statin drugs to lower blood cholesterol. A rapidly growing number are now taking Zetia, another cholesterol-lowering drug, alone or increasingly prescribed with a statin like Lipitor, Zocor, or Crestor. Zetia is proudly advertised on one of its web sites as working differently from statins, “…which work mainly on the liver…Not ZETIA …which is unique in the way it helps block the absorption of cholesterol that comes from food.”

A brilliant marketing strategy emerged back in 2000: Why not combine Zetia with a statin to lower cholesterol even further? This led to the heavily advertised Vytorin, which indeed combines Zetia with the statin, Zocor. Predicted 2006 yearly sales of Zetia alone approaching $5 billion.

Drug makers, Merck and Schering-Plough are now being criticized for not yet releasing data from their important Zetia/Vytorin study, called Enhance, completed early last year. A number of patients have been dropped from the study because of elevated liver enzymes, a Schering-Plough spokesman confirmed last week week, but the number of patients involved will not be available until March.

Schering also said that the FDA had reviewed the unpublished studies and had approved Zetia for use alongside statins, but according to the New York Times, Dec. 21, experts on drug safety confirm once again that the agency has been slow to issue warnings about many widely used drugs. Consider the painkiller, Vioxx, the diabetes medication, Avandia, and the anti-psychotic drug Zyprexa. Five unpublished series involving Vytorin included in the Enhance study, showed possible liver side effects from the drug, yet the FDA approved the drug without significant restrictions on its use. That was in 2004!

This scary news has not yet been making headlines, except in The Times, and I await with interest its future appearance in other major media. The absence so far of network TV coverage should be no surprise, considering the advertising income now being generated by Vytorin. Stay tuned.

Truth and Error in Reporting Clinical Trials: Biases and Blunders

Thursday, December 6th, 2007

An important study was published this week in the JAMA, “Persistence of Contradicted Claims in the Literature.” In it, the authors conclude that “Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials.”*

The authors examined various trials on the effectiveness of Vitamin E for cardiovascular disease prevention, beta-carotene for cancer prevention and estrogen for prevention of Alzheimer’s. They disclosed various biases, adding that genuine diversity of opinion in randomized trials may “lead to a decrease in the absolute frequency of citations…” and a considerable delay to cite contradicted articles long after the published contradictions. They described an interesting bias seen in scientists as well as non-scientists, who may be vulnerable to shared beliefs influencing the interpretation of scientific data, the so-called “wish bias.”

These observations have long been discussed in older medical literature. Odds ratios, as in “this horse is favored 4 to 1” and “P values”, examples of relative differences, are a favorite ploy of drug advertisers and clinical researchers publishing in medical journals. In an important British Medical Journal study the significance of P values was compared with observational data in 260 abstracts of randomised controlled trials in PubMed, and concluded that “Significant results in abstracts are common but should generally be disbelieved.”

Another study examined outcome reporting bias in 519 trials with 10,557 outcomes. The authors concluded that “Incomplete reporting of outcomes within published articles of randomised trials is common and is associated with statistical non-significance. The medical literature therefore represents a selective and biased subset of study outcomes…”

Read this and weep. Better still, maintain a healthy skepticism when the news anchor or TV doctor tells you about the latest blockbuster treatment for cancer, heart disease, or unsightly skin.

* “A clinical trial is an experiment conducted with patients as subjects. … The strongest experimental design …is the randomized design in which patients are randomly assigned to treatment groups. An important distinction in the purpose of clinical trials is that between therapeutic trials (comparing treatment methods) and prophylactic (or prevention) trials.”

Culture, Aggression, Steroids and “Roid Rage”

Sunday, December 2nd, 2007

A group of amazingly diverse biological compounds belong to a chemical class known as steroids.* These substances include, among others, cholesterol, cortisone and its derivatives, vitamin D, digitalis, the sex hormones, estrogen, testosterone, and the synthetic anabolic/androgenic steroids (“AAAS”) abused by body builders and athletes.

One reason for this blog is to reassure those of you taking steroids for legitimate medical reasons. If you are on testosterone or estrogens (sex steroids) for treatment of endocrine dysfunction, hormone replacement, or glucocorticoids (cortisone-related steroids, grouped under “corticosteroids”), for treatment of a vast spectrum of medical conditions, (various forms of arthritis, collagen diseases, skin, kidney disease, Crohn’s, colitis, certain eye conditions, various cancers, organ transplant, etc.): You are not at risk for serious aggression or ” ‘roid rage,” although mental and emotional effects of steroid treatment can certainly occur on long term or high dose corticosteroid therapy.

Patients on corticosteroid treatment for a medical condition are thus to be distinguished from steroid abusers, especially body building types and weight lifters taking extremely large doses of anabolic/androgenic steroids (AAS). These doses may change a person’s self-image and result in violent mood swings, euphoria, suicidal tendencies, and especially violent antisocial behavior. The association between AAS and aggression (” ‘roid rage”) is widely accepted in the resistance training subculture and in the mainstream media (extreme sports, wrestling, boxing), and has been bolstered by the use of AAS “induced rage” as a legal defense.

But then violence and aggression, associated with steroid abuse or not, has become accepted by the public and fans as an alluring attraction of many spectator sports, including, but not limited to hockey, football, soccer, and basketball, where indeed anabolic/androgenic steroids are also widely abused. As we become more inured, if also threatened, by violence occurring in the form of everything from crime shows to regional wars and the worldwide epidemic of terrorism, one wonders when and where chemically-induced aggression plays a role. The following news item is quite scary, but don’t look for much follow-up coverage:


 

One quarter of Blackwater security guards in Iraq use steroids and other “judgment-altering substances,” according to a lawsuit filed by the families of several Iraqis killed or wounded in a Baghdad shooting in September.

Blackwater denies the charges.

*For those interested in chemistry, the class, steroid, refers to a “terpenoid lipid characterized by a carbon skeleton composed of four fused rings generally arranged in a 6,6,6,5 fashion.” Variations are created by attached functional groups.