Archive for January, 2008

Vitamin C Redux

Thursday, January 31st, 2008

A 31-year-old Australian woman who received a kidney transplant with good early graft function later died as a result of calcium oxalate deposits that led to failure of the transplanted kidney. The tragic case, recently reported in the New England Journal of Medicine was attributed to ingestion of 2 grams (2,000 mg.) of vitamin C daily for three previous years while she was on dialysis.

The authors point out that excess ascorbate (Vitamin C) is normally excreted harmlessly in the urine, but in patients with renal failure, it is retained and converted to insoluble oxalate and can accumulate in multiple organs, as is shown vividly in the photographs.

Oxalate-induced kidney failure has also been reported in people with no apparent kidney problem. Oxalates are found in a variety of fruits, vegetables, nuts, and many other foods.

Megadose vitamin C therapy is dangerous and should be avoided.

Medical Trials: What Gets Published?

Tuesday, January 29th, 2008

A group of researchers reported in the New England Journal of Medicine Jan 17 (N Engl J Med 2008:358:252-60) results from FDA-reported studies of 12 antidepressant agents involving over 12,000 patients. They then searched the medical literature to identify matching publications and compared the published outcomes with the outcomes of the FDA-reported studies.

According to the published literature 94% of the studies appeared to have a positive outcomes. By contrast, the FDA analysis showed that 51% were positive. Among 74 FDA-registered studies, 31% were not published. 22 studies viewed by the FDA “as having negative or questionable results were either…not published or published in a way that, in our opinion, conveyed a positive outcome (11 studies).”

In summary, it appears there is extreme selection bias toward positive results in reporting these clinical trials. Although the cause might have been due to “failure to submit manuscripts…or decisions by journal editors and reviewers not to publish,” this would seem in my view, to be extremely unlikely. In any event, the authors of this paper concluded that “Selective reporting of clinical trial results may have adverse consequences…” (To put it mildly).

I hope this shocking article receives the media coverage it deserves.

Re-Defining or Inventing Disease:The Medicalization of America

Sunday, January 27th, 2008

In 1978 in a remarkably candid Fortune article Henry Gadsden, CEO of Merck announced he would like to see his pharmaceutical giant “be more like chewing gum maker Wrigleys” since it had long been his dream to make drugs for healthy people, so Merck would then be able to “sell to everyone.” Ten years later, Lynn Payer would write on Disease-Mongering: “…widening the boundaries of illness: the selling of sickness, and growing the markets for those who sell and deliver treatments.”

Mistaking medical treatment for health care, we are deluged with redefinitions of such universal life experiences as personality quirks, now “social anxiety disorder,” and minor gastrointestinal complaints, re-defined and expanded into GI reflux and irritable bowel syndrome. Moreover, normal muscle aches and pains become “fibromyalgia” and even risk factors such as high cholesterol, are being defined as disease. The very concepts of health and illness are being reframed, resulting in a spectrum of normal complaints and behavior routinely being advertised as widespread, severe, and treatable with medication.

We are learning how informal alliances of pharmaceutical corporations, public relations companies, doctors’ groups, policy makers, and patient advocates promote these ideas to the public.* Along with the media these alliances popularize previously little-known conditions, such as “restless leg syndrome.” In some cases large diagnostic categories have been defined, for example, “female sexual dysfunction” where there has been a serious attempt to convince the American public that 43% of women live with this condition.

The case for bigger and better erections resulted in a $2 billion a year sales of Viagra when Pfizer redefined erectile dysfunction to include men of virtually any age going out on a date. Then there is the Eli Lilly–sponsored promotion of “premenstrual dysphoric disorder,” regarded by many as a nonexistent condition, to help sell their renamed version of the antidepressant Prozac© (rebranded as Serafem©)

More on disease mongering and other redefined or expanded conditions can be seen at the Public Library of Science (PLOS) website.

*This is not to deny there exists large numbers of Patients who can be helped by the publicity and marketing devoted to their disorder and its treatment. I admit the issue resolves finally into a circular argument: the definition of a patient depends on how or who defines his disease or condition.

Creating Diseases

Friday, January 25th, 2008

An archipelago of unexplained symptoms is the reason for over 100 million doctor visits a year. A vast medical literature indicates that certain complaints, often described as “unexplained” are exceedingly common in the general population. The word “somatization”, more accurate and less stigmatizing than hypochondriais, describes patients whose emotional problems seem to be translated into bodily (somatic) complaints. Large studies have shown that 80% or more of all healthy people experience at one time or another a virtual mixed salad of bodily symptoms. Among the most common ingredients are: joint and muscle aches and pains,fatigue, weakness, irritability, faintness or dizziness, headaches, insomnia, sleepiness, nausea, constipation, diarrhea, sweating, etc. What most of these complaints have in common is their unexplained occurrence, their lack of abnormal physical or laboratory findings, and most important of all, their usually benign clinical course.

Some of these complaints, once they receive a name from the medical establishment form a new church called “diagnosis,” and overnight millions of new converts appear out of the previously healthy population. These co-religionists, now termed “patients” flock to doctors, buy new drugs fashioned for their disease, form support and advocacy groups, and metastasize into web sites. On balance this may not turn out to be a bad thing. After all, millions of sufferers now have a Name for their complaint, physicians and drug companies to nurture them, and, above all social respectability.

On the other hand, for those who question whether certain complaints are indeed a new disease, the issue often comes down to economics. Do doubters have the right to deny fellow citizens the wellness ritual: drugs, diets, and doctors, even if the cost threatens to bankrupt the healthcare system?

For my part, I am anxiously awaiting breakthrough medical articles on “Age-Related Stress Envelopment” or ARSE, previously known as midlife crisis. Then I can finally obtain health insurance coverage for this disabling condition.

Fibromyalgia:Does it Exist? II

Thursday, January 24th, 2008

In general, a syndrome is a collection of clinical or laboratory findings occurring together. Thus, we have “epilepsy syndromes,” “stroke syndrome,” “Down’s”, “AIDS” and a dictionary of other syndromes. A diagnosis, disorder, or disease is defined by an ICD-9 code, the International Classification of Disease used for decades throughout the world. Yet no coding scheme for medical diagnosis or treatment can be all-inclusive or unambiguous. Words like “abscess,” “anemia” and “intersex”, challenge any classification, so we slip into terms such as condition, or disorder in the belief that giving something a name still allows us to categorize.

But Fibromyalgia does have a code: according to ICD-9, it is 729.1, including “Other disorders of soft tissues, Myalgia and myositis, unspecified.” Does that make it real? In One way, certainly, since it allows doctors and hospitals to bill for it. Are there other conditions whose existence is validated by an ICD-9 or ICD-10 code? Indeed, yes. Sometimes this can present problems, especially when a syndrome is fictitious or invented. Am I simply begging the question? A slippery place to end up.

More to come.

Fibromyalgia: Does it Exist?-I

Saturday, January 19th, 2008

Can 11 million Google hits on “fibromyalgia” be believed? Pfizer, thanks to FDA approval last year is now advertising Lyrica, an anti-epileptic drug also used for nerve damage, as the new miracle treatment for what they call (with a wink?), a “real disease,” fibromyalgia. In the first nine months of 2007, Pfizer spent over $46 million in advertising, and prescriptions for the drug are approaching 1 million a month. But is fibromyalgia, whose very existence is now questioned by a large number of physicians, a disease, a syndrome (collection of symptoms), or simply another name for plain old “aches and pains”? The doctor who wrote the now classic 1990 paper defining it as widespread pain, mostly of middle-aged women, of unknown origin, without definite physical or laboratory findings, now claims he was wrong, that the disease does not exist. He accurately predicted that Lyrica and the other drugs taken to relieve sufferers will be consumed by millions of people who do not need them. Yet advocacy groups, many partly supported by drug companies, and tens of thousands of physicians who treat fibromyalgia estimate that 6-12 million Americans suffer from the disorder.

Dr. Nortin Hadler, a reheumatologist and professor of medicine at the University of North Carlolina who has written extensively on fibromyalgia, stated, “These people live under a cloud. And the more they seem to be around the medical establishment, the sicker they get.” Dr. Frederick Wolfe, the lead author of the original paper referred to above, and Director of the National Databank for Rheumatic Diseases, referred to by the New York Times (Jan.14, 2008), says he has become cynical and discouraged about the diagnosis, and now considers the condition a physical response to stress, depression, and economic and social anxiety.

Most interesting, Lyrica, its mode of action on the brain and nervous system unclear, was originally developed as an anti-depressant, since it raises levels of serotonin, like the SSRI drug class to which Prozac, Paxil, Zoloft, Effexor, Cymbalta, etc. belong. Moreover, Lyrica been used off-label (unapproved, but legal use) by many physicians as an anti-depressant. Yet the drug is not without problems of toxicity, such as widespread swelling or edema, dizziness, blurring of vision, acute allergic reactions, and especially common, severe weight gain.

The argument over the existence of fibromyalgia brings up many perplexing questions to be discussed in my next blog, namely, what do we mean when we give some collection of complaints a name, and what indeed are “medicalization,” “somatization,” and “disease mongering”? Do we ignore millions of patients by depriving them of their (debilitating) disease and possible treatment, or are we saving them from exposure to another potentially risky drug and billions of dollars in needless medical attention?

More on Plavix, Aspirin, Zetia, and Vytorin

Wednesday, January 16th, 2008

The push to promote Plavix took on another dimension when it involved the strange case of “aspirin resistance.” This is a controversial condition, first described in 2002, which is being used to discredit aspirin, a drug first trademarked by Bayer in 1899. So-called aspirin resistance has fueled the rise of companies, such as Accumetrics and Dade Behring, recently acquired by Siemens Healthcare Diagnostics,which develop, manufacture, and market tests for aspirin/platelet resistance. This is but another success story for Plavix and its admirers and a subtle blow against aspirin.

Many doctors get kickbacks for recommending these tests or have them done in house. Insurance companies don’t pay for them, but some heart attack victims are persuaded by their physicians that it makes no sense to take aspirin for the rest of their lives if they are “resistant” and not getting optimal results. Plavix would seem to be the obvious alternative. Another example of Big Pharma abuse is that the Plavix patent was due to expire next month but they got a 3 year extension based on a study in China for another indication. Apotex had approval for a generic to be available the next month but they received $60 million to hold off until eight months before the new patent expiration date in 2011. This plan backfired when the cash payment became the subject of a Justice Department investigation.

Apotex immediately began marketing the drug while the patent was still in force. As a result, the cost of Plavix has already dropping by 50% and may drop another 30% or more. Bristol-Myers-Squibb is now being sued by health plans and other fiscal intermediaries since this deal may violate federal antitrust laws.

The latest news on Zetia and Vytorin came out the other day, and is being featured in the major media: Merck and Schering-Plough released the results of a study (the Enhance Trial) showing these drugs failed to benefit patients in a two-year trial ending in April 2006. The House Energy and Commerce committee is investigating why the companies sat on their findings of this negative study for over 19 months.

Plavix, Coumadin, and Aspirin: The Anticoagulant Network

Friday, January 11th, 2008

Anticoagulants (“blood thinners”) are widely used and overused in medicine. The combined use of these drugs, particularly aspirin with coumadin or Plavix© has received a great deal of attention recently, and increasing apprehension. The supine acceptance by the medical profession of the blood thinner, Plavix, is a frightening example of the results of a pharmaceutical media blitz. Thanks to manipulative marketing, sales of the drug, made by Sanofi-Aventis, distributed here by Bristol-Myers Squibb, are up 60% in the past two years to over $6 billion worldwide, making Plavix second only to Lipitor© as the best selling drug in the world!

But is it possible that Plavix is safe, and at the same time a therapeutic triumph that saves lives? The drug interferes with blood coagulation by a mechanism different from aspirin and is routinely used to prevent clots developing before and after the placement of cardiac stents. However, its safety and superiority over aspirin and heparin in pre-treatment before stent placement has been widely questioned.

Plavix alone or combined with aspirin, is also used for hundreds of thousands, if not millions of patients, who are assumed to be at increased risk for heart attacks and strokes. However, a study of 15,000 patients published last year found that adding Plavix ($1.50-$3.00 a day) to low dose aspirin (2-3 pennies a day) was no more effective than aspirin alone for preventing heart attacks, strokes, and cardiovascular deaths. In fact, Plavix plus aspirin, a risky combination, nearly doubled the heart disease death rate, and caused many patients severe bleeding problems, especially in elderly patients with minor head trauma.

The New England Journal of Medicine (NEJM) published a study three years ago showing that patients taking Plavix, experience more than 12 times as many ulcers as patients who take aspirin plus a heartburn pill. Up to half of those now taking Plavix do so because their doctors assume that Plavix is safer on the stomach than aspirin, said the study’s lead author. Another article in the NEJM (Oct. 3, 2007) pointed out the dangers of dual anticoagulant therapy (Plavix or Coumadin with aspirin) “…Increased risks not always offset by benefit…”, meaning serious or life-threatening bleeding.

The practice of prescribing drugs for a purpose outside the scope of the drug’s approved label, (off-label use) represents another Plavix problem, with an increasing number of physicians using the drug where it is not indicated. John LeCroy, a drug analyst stated “It’s a massive drug right now. It already gets massive use, a lot of it off-label.” The same article reported that the FDA granted fast-track review process for Plavix, that is being considered for an additional use: the treatment of a certain type of heart attack.

The anticoagulant conspiracy represents a new multibillion pharmaceutical dollar growth industry backed by investors inspired by authorization of coverage by Medicare and private insurers. For further revelations and detailed documentation of these and numerous other conflicts of interest and widespread corruption in industry, medical centers, and the medical profession see this site , Dr. Paul Rosch’s, The American Institute of Stress and its Newsletter, especially, the June 2006 issue.

A word of advice: If your doctor has you on aspirin plus coumadin or aspirin plus Plavix, (or Plavix alone for heart or stroke prevention), ask him to tell you the indications, the benefits, and the risks.

Deliberately Misleading Drug Studies: Is it a Medical Shell Game?

Sunday, January 6th, 2008

To appreciate how easily people and most physicians can be fooled, consider this: Which drug would you rather take, one that reduces your risk of cancer by 50 percent, or another drug that only reduces your risk of cancer from two to one out of 100? Most people would choose the drug that reduces their risk of cancer by 50 percent, but in fact both these numbers refer to the same outcome. They’re just two different ways of looking at the same numbers. Without any qualification, both statements “reduced the risk by 50%” and “reduced the risk by 1 in a hundred” (1%) are examples of absolute or relative difference. But note the difference in “feel” between 50% and 1%. Which figure sticks in your mind?

So the use of one definition “relative risk” in particular is both misleading and dangerous, especially when drug promotion is involved. Most clinical researchers using data to compare two or more different groups, almost always present their results in confusing ways to emphasize a point of view. An absolute difference is a subtraction; a relative difference is a ratio, but they’re just two ways of propagating confusion by expressing a result by using two different sets of numbers. Of course, they don’t always supply all the numbers, especially the Absolute differences.

For example, the headlines read, “Tamoxifen Cuts Breast Cancer Risk by 33% in Healthy Women!,” yet it turns out, among all the women in a study who took Tamoxifen, less than 2% got breast cancer, and among those that took the placebo, less than 3% got breast cancer. The real difference was 1%, in this series, of questionable significance.{“How to Lie With Statistics,” Real Health Breakthroughs, Dr. William Campbell Douglass, 2004}

Keep in mind that headlines promoting a drug will almost always refer to relative risk, “A breathtaking 40% reduction in risk!” -and this numerical shell game will be copied in the mainstream media, press, medical journals. Pharmaceutical companies, marketing reps, even some physicians anxious to publish and usually supported by commercial drug interests are constantly pushing and exaggerating the supposed benefits of their drugs while minimizing their risks. As the old saw goes: Figures don’t lie, but liars can sure figure.

More to come.

Martin F. Sturman, MD