Would doctors take the medications they prescribe to their patients? Not necessarily, if a recent article in Men′s Health is any indication (1). A number of physicians were asked which drugs they themselves would refuse to take. Here is their list:

• Asthma drug Advair
• Diabetes drug Avandia
• Pain reliever Celebrex (a relative of the infamous Voixx)
• Antibiotic Ketek
• Heartburn medication Prilosec
• Heartburn medication Nexium
• Eye drops Visine Original
• Decongestant Pseudoephedrin

The doctors questioned also suggested alternative treatments. Unfortunately, all they could come up with were other drugs! You can find their recommendations in the original article (1).

I first came across this list on Dr. Mercola′s site (2). Here is the beginning of his commentary:

"Seemingly positive and helpful articles like these really highlight how pervasive the conventional drug culture is. Although these drugs are exposed as being dangerous and best avoided at all costs, the writer failed miserably in providing ′healthier′ alternatives; in all cases but two, merely citing alternative drug treatments …" (2)

Actually it was the doctors who failed miserably; the writer just quoted the doctors′ recommendations. Mercola then goes on to comment on three of the drugs on this list — the asthma, diabetes and heartburn / acid reflux medications — and suggests non-pharmaceutical alternatives. I′ll restrict my own comments to Avandia.

In May of 2007 the U.S. Food and Drug Administration (FDA) issued a safety alert on Avandia (3):

"The U.S. Food and Drug Administration (FDA) is aware of a potential safety issue related to Avandia (rosiglitazone), a drug approved to treat type 2 diabetes …" (3)

The agency goes on to say that safety data from some controlled clinical trials showed a potential increase in the risk of heart attacks, but other data provided contradictory evidence. The agency then issues this warning to patients on Avandia:

"Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes." (3)

Why didn′t the FDA just mandate the removal of the drug from the market?

"FDA′s analyses are ongoing. FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies. Pending questions include whether the other approved treatment from the same class of drugs, pioglitazone, has less, the same or greater risks. Furthermore, there is inherent risk associated with switching patients with diabetes from one treatment to another even in the absence of specific risks associated with particular treatments. For these reasons, FDA is not asking GlaxoSmithKline, the drug′s sponsor, to take any specific action at this time." (3)

If changing treatments poses such a significant health risk, why advise patients to talk to their doctors about their available treatment options, i.e. about switching drugs? And exactly what was the information available to the agency that made it so difficult for them to make a decision?

"Recently, the manufacturer of Avandia (GlaxoSmithKline) provided FDA with a pooled analysis (meta analysis) of 42 randomized, controlled clinical trials in which Avandia was compared to either placebo or other anti-diabetic therapies in patients with type 2 diabetes. The pooled analysis suggested that patients receiving short-term (most studies were 6 months duration) treatment with Avandia may have a 30-40 percent greater risk of heart attack and other heart-related adverse events than patients treated with placebo or other anti-diabetic therapy. These data, if confirmed, would be of significant concern since patients with diabetes are already at an increased risk of heart disease." (3)

Of significant concern? Can you imagine a natural health product remaining on the market with a rap sheet like that. Does the pharmaceutical industry control the FDA, or what?

The sad thing about all of this is that type 2 diabetes is considered a life style disease that is both preventable and reversible. The American Diabetes Association readily admits this:

"People with diabetes have the same nutritional needs as anyone else. Along with exercise and medications (insulin or oral diabetic pills), nutrition is important for good diabetes control. By eating well-balanced meals in the correct amounts, you can keep your blood glucose levels as close to normal (non-diabetic level) as possible." [emphasis added] (4)

Pharmaceutical intervention shouldn′t even be necessary in type 2 diabetes. Yet the drug peddling continues, with the active participation of the medical establishment.

Sources:

1. Morgan Lord. 8 Drugs doctors would never take. If they don't use these medications, why should you? Men's Health June 22, 2008. [Full Text]
2. Dr. Mercola. 8 Drugs doctors would never take. Mercola.com July 10, 2008. [Full Text]
3. FDA issues safety alert on Avandia, May 21, 2007. [Full Text]
4. Nutrition & Recipes. American Diabetes Association. [Quote]

In my last post (Pharma tricks - "key opnion leaders") I commented on an article in the British Medical Journal (1) about pharmaceutical companies hiring leading medical specialists to front for them. The fact that this article appeared in a major medical journal shows that doctors are getting concerned about the undue influence of the pharmaceutical industry on medical practice. The general public should be even more concerned, since we are the guinea pigs. Unfortunately, too many people are unaware of this cosy arrangement between the pharmaceutical industry and the medical establishment.

Just how substantial pharmaceutical "consulting fees" can be was revealed in a June 8, 2008 article in the NY Times (2). The report concerned a group of Harvard child psychiatrists, two of whom were paid at least $1.6 million and the third at least $1 million, from 2000 to 2007. What prompted this exposé was the fact that none of these prominent medical doctors declared their outside incomes to Harvard as required by university conflict-of-interest rules. Lying about their nice fat cheques from drug makers also violated the conflict-of-interest rules of the U.S. National Institutes of Health (NIH) which partially funded their work.

These facts came to light as the result of a U.S. Congressional investigation into the relationship between the pharmaceutical idustry and the medical establishment. Drug companies have replaced the U.S. federal government as the major source of research funding, and law makers have become concerned about the undue influence of industry money on the integrity of medical research.

Obviously, both the drug companies and the medical doctors participating in this scam want to keep this financial arrangement quiet. The whole purpose of this subterfuge is to give the appearance of scientific objectivity, which is obviously out the window once the scale of these payments becomes known. Drug makers cannot hide their involvement in clinical trials; they sponsor these trials, and it is their drugs that are tested. However, the amount of money that is paid to outside researchers speaks volumes about the credibility of the results. Compensation for time spent is one thing, and apparently annual outside revenues of less than $10,000 dollars needn't be reported to universities. But one simply has to believe that payments of a million dollars or more over a period of seven years buy a good deal more than just time.

What did drug money buy in this case? Apparently it bought a whole new pharmaceutical market. These Harvard researchers "discovered" that a large number of children and adolescents suffer from dipolar disorder, a mood problem formerly thought to be confined to adults. They promoted the aggressive diagnosis and treatment of this condition with anti-psychotic drugs. Conveniently, it wasn't even necessary to develop new drugs — anti-schizophrenic drugs are prescribed for this newly discovered disease.

The result of all this was a huge increase in diagnoses and prescriptions for this condition. According to the same NY Times article, "Some 500,000 children and teenagers were given at least one prescription for an antipsychotic in 2007, including 20,500 under 6 years of age, according to Medco Health Solutions, a pharmacy benefit manager." (2)

Not all researchers agree with the Harvard trio on childhood dipolar disorder. Some consider the clinical studies "proving" the condition poorly designed and the results inconclusive. The biggest problem in this field is the fact that assessment of symptoms is subjective; it is difficult to prove the diagnosis or to disprove the success of pharmaceutical intervention. What better "health" field could you find if you wanted to invent a disease to make money?

"The price we pay for these kinds of revelations is credibility, and we just can't afford to lose any more of that in this field", another researcher is quotes as saying. "In the area of child psychiatry in particular, we know much less than we should, and we desperately need research that is not influenced by industry money." (2)

How credible are the findings of researchers who lie about their financial links to the drug companies sponsoring their studies? And it is unlikely that problems of this sort are restriced to the field of child psychiatry. So much for "evidence-based" medicine.

Sources:

1. Key opinion leaders: independent experts or drug representatives in disguise? R. Moynihan. Brit Med J 2008;336:1402-1403. [Full Text]
2. Researchers fail to reveal full drug pay. Gardiner Harris and Benedict Carey. NY Times June 8, 2008. [Full Text]

What on earth are key opinion leaders (KOLs)? In the world of medicine they are influential doctors who help pharmaceutical companies sell drugs (1,2). Drug companies realized that doctors don′t like to be ″educated″ by drug reps, but will listen to their medical colleagues. So they set out to recruit leading specialists to pitch their drugs — for a handsome fee of course. This seems to be a worldwide phenomenon.

″[Key opinion leaders] can influence thousands of prescribers and hence prescriptions through their research, lectures, publications and their participation on advisory boards, committees, educational boards, professional societies and guideline/consensus document development.″(2)

Typically KOLs lecture at company-sponsored events, using company-supplied material and saying what the companies want them to say. KOLs are also referred to as thought leaders; this presumably makes the medical doctors in their audience thought followers, not exactly reassuring if you are a patient.

How can pharmaceutical companies be sure that they′re getting their money′s worth from any given KOL? Drug companies actually have access to prescription records, incredible as it may sound. They routinely track prescriptions before and after every presentations, i.e. they can calculate their return on investment in their KOL to the Dollar; KOLs that don′t live up to expectations get dumped. Those that ″perform″ get paid quite handsomely. Typical fees might be $3000 per lecture, $200 per hour for participating in clinical trial, etc (2).

Sometimes a disgruntled drug rep quits and spills the beans. These former pharma employees make it very clear that drug companies consider KOLs sales people. But you don′t even have to listen to former sales reps; it all happens in broad daylight. In fact, the KOL practice has even spawned a niche business sector. Enter "key opinion leader management" in a search engine to see what I mean. There are actually central databases of opinion leaders, showing their return on investment (2).

What is wrong with all this?

Pharmaceutical companies will do anything to maximize profits, whether their drugs benefit patients or not. Their own pronouncements will be perceived as self-serving — drug companies have little credibility left. By persuading prominent doctors to front for them, their sales pitches appear to be objective presentations by independent experts. And this practice does seem to influence prescribing physicians, to the detriment of their patients.

It is bad enough that continuing medical education courses can be turned into pitch fests. At least the physicians in the audience know that these events are put on, and the speakers paid, by pharmaceutical companies. One would therefore hope that they take what they are told with a grain of salt.

But how are doctors to know which medical articles published by prominent physicians are trustworthy? The companies sponsoring the studies have the power to decide what gets published, and they are not above fudging results. Worse still, the supposed authors may not even have been involved in ″their″ studies, but were simply paid to put their names on publications (yes, this happens!).

It seems though that the ultimate use that pharmaceutical companies can make of KOLs is to get them on advisory boards and committees, where they can influence policies and standards of medical treatment that favour the firms they represent and the pharmaceutical industry in general.

What is the solution?

Medical doctors are now required to declare all sources of funding and potential conflicts of interest in their publications. This is of course a step in the right direction, but one wonders if one gets the whole truth. It is certainly not in Big Pharma′s interest to disclose their financial dealings, since it defeats the purpose of working with KOLs, whose principal asset is after all their perceived integrity.

I would think that patients′ best protection is to know as much as they can about health matters. Our health has to be our own concern, not something to be managed by doctors with pharmaceutical products.

Key opinion leaders — the best integrity money can rent!

Souces:

1. Doctors for pharma. Physician ″opinion leaders″ — helping or hurting medicine? The Scientist Community June 20, 2008
2. Key opinion leaders: independent experts or drug representatives in disguise? R. Moynihan. Brit Med J 2008;336:1402-1403.

Are you taking ASA (aspirin) to lower your blood pressure? If you do, take it before going to bed!

People with pre-hypertension (<140/90 mm Hg) taking 100 mg ASA per day showed statistically significant drops in both systolic and diastolic blood pressure (-5.4/-3.4 mm Hg), but only if they took the medication before going to bed. (1). There was no blood pressure change when ASA was taken in the morning. Pre-hypertension is a risk factor for cardiovascular disease.

The same researchers had earlier found the same pattern in patients with mild hypertension (2). Only ASA taken before going to bed resulted in blood pressure drops (-4.9/-3.5 mm Hg). Blood pressure varied throughout the day, but after evening ASA administration it remained consistently lower all day, compared to pre-treatment values.

It isn't known why taking aspirin is more effective at night. One possible explanation is better absorption by the gastrointestinal tract at night. ASA taken before going to bed may also slow the production of hormones and other substances that may cause clotting, many of which are produced by the body at rest. (1)

This drop in blood pressure at night only holds true for low doses of ASA. The much larger amounts taken for anti-inflammatory effects (500 mg/day or more) may actually increase the blood pressure, even if the medication is taken at night. However, even there it is still better to take ASA before going to bed. Doses of 1300 mg of ASA at night resulted in 37% fewer gastric hemorrhagic lesions, i.e. even large doses of ASA are better tolerated at night. (2)

Sources

1. Aspirin at bedtime lowers blood pressure. HealthDay News May 14, 2008.
2. Hermida RC et al. Administration time-dependent effects of aspirin on blood pressure in untreated hypertensive patients. Hypertension 2003;41:1259-1267.

Two recent articles in the New England Journal of Medicine dealt with problems at the U.S. Food and Drug Administration (FDA), particularly the lack of public confidence in the agency and the need for reform (1,2). The FDA oversees 25% of the U.S. consumer economy, from food to cosmetics, drugs and medical devices. (2)

"Public opinion polls show that confidence in the FDA fell from 80% in the 1970s to 36% in 2006 - ratings usually reserved for tobacco companies and used-car dealers." (2).

The authors specifically mention the Vioxx scandal, the heparin contamination, and a recent decision by the U.S. Supreme Court concerning medical devices:

"[The Supreme Court] ruled in February that FDA approval of a medical device precluded lawsuits brought by patients against the manufacturer over adverse events in state courts. ... [This leaves] patients without recourse if the FDA has certified that a medical device is generally safe and effective. In effect, FDA approval is now a shield protecting a manufacturer from subsequent claims - a role the agency undoubtedly never intended to play. A similar case, involving drugs, will be argued before the Court this fall." (2)

Problems with adulterated drugs, like the heparin affair, are blamed on the fact that today 80% of all active pharmaceutical ingredients (APIs), i.e. starting materials for drugs, are imported from factories with questionable safety standards, primarily in China and India. The heparin contamination, for example, was traced to a Chinese supplier. The FDA monitors foreign manufacturers of APIs, but doesn't have the resources to do a thorough job.

The authors go on to point out that it is the FDA's mandate to inspect producers of both drugs and chemicals used to manufacture drugs, in order to certify that plants meet the current Good Manufacturing Practice (GMP) standards. This includes the inspection of factories abroad. One author then goes on to say that:

"... It is inappropriate and unrealistic to expect the FDA to ensure the integrity of every manufacturer's entire supply chain. If a manufacturer chooses to save money by purchasing raw material from China, then it must bear the additional costs of zealous quality control and oversight in a country with a very limited regulatory system and a fluid commercial structure. ... U.S. taxpayers shouldn't have to pay to send inspectors to every factory in China to allow industry to obtain cheaper and largely unregulated products there." (2).

The authors rightly point out that the adulteration of drugs cannot be prevented solely by regulatory agencies. It has to be the responsibility of the manufacturer, with the FDA providing the regulatory framework. To rectify the situation, the authors call for holding manufacturers responsible for the safety of their products, and for increased funding for the FDA:

"The public's health is at stake, and the time for adequate funding of the FDA is now." (2).

It may well be that the FDA is underfunded, but the key to food and drug safety is surely to hold manufacturers responsible for what they sell. Given Merck's behaviour in the Vioxx affair, it is unlikely that Big Pharma will act responsibly without the threat of lawsuits. The recent decision by the U.S. Supreme Court concerning medical devices has obviously lessened even that threat, although a case involving drugs has yet to be decided. Even the threat of lawsuits doesn't seem much of a deterrent though. Settlements of class action suits in the billions still leave the richest pharmaceutical companies with net profits from selling products that harm. The financial, if unethical, bottom line is that lawsuits are just part of doing business.

This leaves regulatory oversight, which brings us back to Americans' low opinion of the FDA. This low opinion has little to do with the agency's lack of funding, and throwing money at the problem isn't going to restore public confidence. The problem is simply the public's perception that the agency is controlled and corrupted by the very industry it is supposed to oversee.

Sources

1. Schweitzer SO. Trying times at the FDA - The challenge of ensuring the safety of imported pharmaceuticals. N Engl J Med 2008;358:1773-1777.
2. Wood AJJ. Playing "Kick the FDA" - Risk-free to players but hazardous to public health. N Engl J Med 2008;358:1774-1775.

The February 14, 2008 issue of the New England Journal of Medicine ran an article with the astonishing title "Does preventive care save money?" (1). That analysis was prompted, according to the authors, by the health care campaign promises made by various U.S. presidential candidates.

The very question - whether preventive care saves money - seems astonishing enough. But prevention surely isn't just about money. I'd rather not get sick in the first place, even if "curing" me wouldn't cost any more than preventing my disease. Medical treatment is one of the leading causes of death, and I'll take my chances with prevention.

The authors do concede that prevention might just do some good:

"Indeed, some evidence does suggest that there are opportunities to save money and improve health through prevention."

But then they go on to say:

"Although some preventive measures do save money, the vast majority reviewed in the health economics literature do not."

What on earth are these authors talking about? When one reads further one discovers that they aren't discussing what you or I would consider prevention at all. The article is primarily about early diagnosis to detect malignancies in their most treatable stages. In other words, the authors' interest is restricted to medical interventions. Only one sentence in the article pays lip service to genuine disease prevention, and then it's back to medicine:

"Preventable causes of death, such as tobacco smoking, poor diet and physical inactivity, and misuse of alcohol have been estimated to be responsible for 900,000 deaths annually - nearly 40% of total yearly mortality in the United States."

It turns out that the cost of preventive medical interventions actually isn't all that different from the cost of treating diseases. The reason for this, the authors point out, is that too many unnecessary diagnostic tests are performed. For screening to be cost-effective, it should only target populations at high risk for a given disease. The authors' prescription for achieving better health results:

"Conduct careful analysis to identify evidence-based opportunities for more efficient delivery of health care - whether prevention or treatment - and then restructure the system to create incentives that encourage the appropriate delivery of efficient intervention."

I can't help thinking that the authors of this paper are as naive as the presidential candidates with their proposed solutions to the "health" care crisis. What kinds of incentive can you create for service providers by cutting back on spending?

Why is U.S. "health" care so expensive? Because providing it is so lucrative. The more "services" can be provided, even if they are totally ineffective, the more enormous the profits for the service providers. Vested interests will fight any expenditure reductions on preventive interventions tooth and nail.

In fact, an enormous amount of money is spent by the "health" care industry on preventing prevention. Big Pharma has no intention of giving up their customers without a fight. They are spending huge sums of money to influence legislators, regulatory agencies, and medical professionals. Supplement manufacturers cannot make perfectly well-supported health claims, and compounding pharmacies are prevented from supplying bio-identical hormones, to give just two examples of the nefarious influence of the pharmaceutical industry. I would think that the providers of diagnostic services will also fight any cost-effectiveness measures, i.e. any reductions in their profits.

The solution to the "health" care crisis won't come from the medical establishment or from Big Pharma. Our best hope to be healthy is to be informed and proactive. We do need medical care for certain problems, but our health is our own responsibility.

Sources

1. Cohen JT, Neumann PJ, Weinstein MC. Does preventive care save money? Health econmics and the presidential candidates. N Engl J Med 2008;358(7):661-663.

Well, I finally got around to checking out Mark Joyner's blogging course, and I must say that it is an excellent introduction to the subject. Mark teaches you what your blog needs to have, how to drive traffic to your blog, and how to make money with it. Here are some of the things you'll learn:

Creating your blog

• Why your blog needs to focus on a specific topic, and why you need to choose a topic that interests you.
• Why it is important to develop a list of keywords for your chosen niche and use them in your titles and your text, and how to develop such a list.
• Why quality is all-important, and why you need to post regularly to your blog.

Drivng traffic to your blog

• Why the right keywords and incoming links from quality blogs are vital for traffic generation.
• How well-chosen keywords and regular postings increase your chances that you are "spidered" by search engines.
• How you can submit your blog to search engines.
• Why you should alert your readers to other blogs that you find relevant and interesting, and how this gets you inbound links and a higher ranking.
• Why you should participate in forums related to your niche.
• Why you should turn your posts into articles and give them away for free.

Making money with your blog

• How you can earn advertising revenues with programs such as AdSense.
• How you can join affiliate programs with major companies, such as Amazon.com, ClickBank etc and earn commissions.
• How you can earn money as a professional blogger.

There are also a couple of topics that I would have liked to see discussed in more detail. For example, for some purposes it is better to use a website; for others a blog might be more appropriate. That topic could have been treated in more detail. Secondly, there are traffic-generating tools that work for blogs but not for website. That subject too might have been worth a separate lesson.

But these are mere quibbles. The bottom line is that this is an excellent introductory blogging course. Follow Mark's guidelines and you will end up with a first-rate blog. I for one am going to use this course as a blueprint for improving my own.

Sources

1. Harper's Biochemistry, 25th Edition, Appleton & Lange 2000
2. Nutritional Biochemistry, 2nd Edition, Tom Brody, Academic Press 1999

In my last post “Can vitamin C prevent cardiovascular disease?” I alluded to the role of lipoproteins in covering lesions on blood vessel walls and in the development of atherosclerosis. In this and the next few posts I want to talk about the structures and functions of lipoproteins in some detail, before getting back to cardiovascular disease.

What are lipoproteins? They are particles that transport lipids to and from the tissues.

Lipids are fatty acids and their glycerol esters, cholesterol and its fatty acid esters, and the lipid-soluble vitamin families A, D, E and K. Lipids are hydrophobic, i.e. water-insoluble, and special water-miscible particles are required to shuttle them through the bloodstream to the cells that need them. Free fatty acids travel non-covalently bound to the protein albumin. The rest of the lipids are transported in lipoproteins.

The basic structure of lipoproteins is best explained by comparison to cells. The contents of a cell are enclosed by a plasma membrane called a lipid bilayer. The two layers consist of phospholipids and unesterified cholesterol (plus proteins, which we’ll get to in a moment). The hydrophobic ends of the lipids in the two layers point toward each other, and the hydrophilic ends face the inside and outside of the cell, respectively. Both the inside and outside surfaces are hydrophilic, i.e. cells are water-miscible enclosures for hydrophilic content.

Of course the lipid bilayer is only the enclosure. Proteins on the cell surface and in the plasma membrane are needed to control entry of nutrients and exit of waste, for signaling purposes etc. It is the protein components of the plasma membrane that distinguish different cell types.

What happens if you eliminate the inner shell of the lipid bilayer? What is left is a container that is still hydrophilic on the outside, but the inner surface consists of the now exposed hydrophobic ends of the phospholipids and cholesterol molecules. In other words, we now have a water-miscible container for hydrophobic content - for lipids. A particle enclosed by a monolayer membrane is called a micelle, and it is the basic structure of lipoprotein particles.

Again, proteins have to be added to this structure to direct these particles to their destinations and to load and unload their lipid cargo.

In future posts we’ll look at
· The different types of lipoproteins and their functions,
· The surface proteins that determine the behaviour of these lipoproteins, and
· The enzymes that are needed to make the whole system work

To be continued…