The Centers for Disease Control and Prevention released some interesting data yesterday.  They reported that in 2007 an estimated 23.6 million people (7.8% of the total US population) have diabetes.  Of these people, only 17.9 million know they have diabetes, while 5.7 million have not been diagnosed.  The good news is that the percentage of people with diabetes who don’t know it has decreased from 30 to 25% The bad news is that the number of Americans with diabetes is increasing.

Number  of People in the US (in Millions) with Diagnosed Diabetes: 1980- 2005

(from http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm)

How Bad Is a Little Sugar?
As the CDC’s Fact Sheet states, “Overall, the risk for death among people with diabetes is about twice that of people without diabetes of similar age.” Diabetes causes high blood pressure, heart disease and stroke, and is the leading cause of blindness and kidney failure in adults.  Diabetes – because it affects the small blood vessels – also predisposed people to infections, and can lead to amputations from lack of adequate blood flow.  It also increases the risk of pregnancy complications, and leads to nervous system impairments.

How Many People Have Diabetes Where I live?
The CDC doesn’t have county level data for 2007 yet, but the map below shows the percentage of people with diabetes in counties across the country.  [Note – People in Colorado do have diabetes, but in Colorado the country with the highest incidence of diabetes falls just below the threshold for the second color in the map.]

(from http://apps.nccd.cdc.gov/DDT_STRS2/NationalDiabetesPrevalenceEstimates.aspx)

What to Do About Diabetes?*
There are lots of good resources of information for patients about diabetes (see below), but without getting into too many specifics, people should talk to their doctors about three different types of things:

1. Testing: Get tested – both for diabetes as well as pre-diabetes, a condition which indicates impaired metabolism of sugar and a higher risk of developing diabetes.
2. Treatment: Get treated if you have diabetes.  Get treated for the diabetes itself and for other conditions that increase the risk of developing the complications of diabetes, such as high blood pressure and high cholesterol.  And be sure to take your medicines as instructed by your physician, and test your blood sugar as they recommend.  If you don’t understand how to take your medicines or have any questions about them, just ask your doctor or pharmacist.  Quality healthcare professionals would rather answer your questions and prevent problems from developing, than have to help you resolve any problems you develop from taking medicines incorrectly.
3. Personal Choices - Eat Right and Exercise: Whether you have diabetes or are at risk for developing diabetes diet is crucial, and exercise and weight loss can help improve diabetes and lowers the risk of developing diabetes and its complications.

Resources About Diabetes
American Association of Diabetes Educators - www.diabeteseducator.org
American Diabetes Association - www.diabetes.org
Centers for Disease Control and Prevention - www.cdc.gov/diabetes
National Diabetes Information Clearinghous - http://diabetes.niddk.nih.gov/ and http://diabetes.niddk.nih.gov/dm/pubs/stroke/#connection

*DISCLAIMER – THIS INFORMATION IS NOT SPECIFIC MEDICAL GUIDANCE, IT IS NOT INTENDED TO DIRECT TREATMENT OR PREVENTION FOR INDIVIDUALS,  AND SHOULD NOT BE SUBSTITUTED FOR ADVICE FROM PHYSICIANS AND OTHER HEALTHCARE PROFESSIONALS INCLUDING NUTRITIONISTS, AND DIABETES EDUCATORS.

The FDA announced today that they have sent letters to 25 companies to stop selling fake cancer cures. That is, things that the companies claim cure cancer, but have never been tested, or approved by the FDA. The FDA has a web-site with more information about this, and a sub-page that lists 125 Fake Cancer Cures.

I know the FDA gets lots of flack for not doing enough - and not doing it fast enough - I applaud the FDA for taking this action, and encourage them to do more because I have found the advertisement and selling of these non-medicines troubling for a long time.

Cancers are serious diseases by anyones definition, and real medical science is making great strides in developing better treatments and cures, and in overall improving the lives of people living with cancer - both through traditional drugs and biologics, as well as with complementary therapies. But those profiting from selling fake medicines are selling false hope.

I would like the FDA go after more of these people who are profiting from selling fake medicines marketed as cures for other diseases and conditions - particularly ones that may be for symptoms of serious conditions. For example, every time I see the plastic-faced grinning guy on TV hawking a non-FDA approved “natural male enhancement” product, I wonder about all the men who may still be too embarrassed to talk to their physician about their erectile dysfunction problem - which unknown to them is being caused by a serious medical problem, like cancer. And of course for men who are buying this stuff who don’t have ED, then it would be nice if they could talk to their physician about therapy to address the route causes of their feelings of sexual inadequacy.

But of course, the FDA currently has insufficient resources to cover all of it’s multiple priorities - which is why Congress and the Administration are discussing how to provide more funding. Until that happens, I hope the FDA continues being vigilant and stops as many of these purveyors of false hope as they can - at least so these people don’t get the idea that because the FDA’s resources are stretched a bit thin, that the FDA won’t bother them.

Today’s Boston Globe has an article about a study from Children’s Hospital in Boston that explores the high rate of insufficient vitamin D in otherwise healthy infants and toddlers. (12% deficient in vitamin D and 40% with suboptimal levels.) The study also noted that one-third of these children with low levels of vitamin D had pathological bone changes seen on x-rays.

What Does Vitamin D Do?
What the research study did not examine - but the Globe story does mention – is that in recent years there has been extensive investigation and speculation about the role of vitamin D plays in many other areas of health besides strong bones and teeth. For example, the NIH’s Vitamin D Fact Sheet notes that vitamin D may play a role in lowering the risks of certain cancers:

Laboratory and animal evidence as well as epidemiologic data suggest that vitamin D status could affect cancer risk. Strong biological and mechanistic bases indicate that vitamin D plays a role in the prevention of colon, prostate, and breast cancers. Emerging epidemiologic data suggest that vitamin D has a protective effect against colon cancer, but the data are not as strong for a protective effect against prostate and breast cancer, and are variable for cancers at other sites. Studies do not consistently show a protective effect or no effect, however. One study of Finnish smokers, for example, found that subjects in the highest quintile of baseline vitamin D status have a three-fold higher risk of developing pancreatic cancer.

The NIH’s Fact Sheet goes on to note that vitamin D may play a role in preventing diabetes, high blood pressure and multiple sclerosis. A July 2007 review article by Dr. Holick in the New England Journal of Medicine expands upon this information:

The discovery that most tissues and cells in the body have a vitamin D receptor and that several possess the enzymatic machinery to convert the primary circulating form of vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, has provided new insights into the function of this vitamin. Of great interest is the role it can play in decreasing the risk of many chronic illnesses, including common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease.

The fact that vitamin D plays more than one function in the body should not be surprising, since many physiologically compounds serve multiple functions – from neurotransmitters that act in both the GI and CNS systems, to proteins whose breakdown products also have cellular activity. What this points out is that people (and all animals) are not simple biological systems. While I’ll leave a discussion of the exploding field of systems biology for another time, I do want to point out that once we “know” something in medicine it usually means “what we know right now.” As a professor in medical school said “Half of what we’re going to teach you is wrong, we just don’t know which half.” (I think every medical student gets this in some lecture – it must be in the “Medical School Professor’s Crib Notes.”)

So How Much Vitamin D?
This evolving scientific certainty brings us to the question of how much vitamin D people should be getting – and by what route. There is still no academic agreement as to how much vitamin D people should have – although individual needs do depend upon age, gender, skin color, and medical condition (including pregnancy). But there is a growing consensus that most people need more Vitamin D than they are getting.

The three basic routes for getting more vitamin D are supplements, diet, and sun exposure: The latter is somewhat problematic as the rising incidence of skin cancers places greater emphasis on using sunscreen. Supplements are great – particularly for time limited use in select populations like infants who are breast fed. (That was a risk factor in the Children’s Hospital study.) This leaves us with food.

While milk has long been supplemented with vitamin D, milk consumption in adults is very variable – so more foods are being supplemented. Because vitamin D is much more effective when consumed with calcium, vitamin D is increasingly being added to fortified juices, cereals, and now yogurts. In fact, last year, after seeing several articles about the expanding importance of vitamin D (including the NEJM review article) I called Stonyfield Farms to ask why their yogurt didn’t have vitamin D added to it – as did some of their competitors. The person I talked to was very nice, but didn’t have a very convincing answer. However, I recently noticed that Stonyfield yogurts now have added vitamin D. After making this discovery, I found their October 2007 “Moos From The Farm” newsletter that discussed their plans for adding vitamin D to their products over the winter:

Vitamin D in Our Fat Free
When we converted our fat free yogurts to organic on the 1st of this month, we also added vitamin D, which offers a bunch of important health benefits. Vitamin D…

• increases calcium and phosphorous absorption, which decreases the risk of osteoporosis;
• has immune-boosting properties;
• may help to reduce 17 different types of cancer;
• may decrease the incidence of multiple sclerosis;
• helps to maintain optimal muscle strength;
• benefits diabetics and those with hypertension.

We’ll be adding vitamin D to more of our yogurts this winter, so stay tuned!

I would be tempted to say that Stonyfield added the vitamin D as a marketing pitch, but I haven’t seen any ads or labeling changes that now tout, “Now Healthier – With Added Vitamin D!!!,” so I think they did it because it was a good thing to do, they saw the trend towards a greater emphasis on consuming more vitamin D and wanted to be ahead of the movement – and maybe, possibly, perhaps because I called last summer and asked the question.

So while the optimal level of vitamin D consumption is uncertain, taking too much through food seems hard to do. The NIH’s Fact Sheet notes that there doesn’t seem to be any risk of toxicity from too much vitamin D until you get above 2,000 International Units (IUs) per day, and Holick’s NEJM review states that toxicity doesn’t start until you reach 10,000 IU/day. And as the NIH Fact Sheet notes, “High intakes of dietary vitamin D are very unlikely to result in toxicity unless large amounts of cod liver oil* are consumed; toxicity is more likely to occur from high intakes of supplements.” [*Cod liver oil has 1360 IU per tablespoon.]

Talk With Your Doctor and Summertime Eating
So when you’re deciding about what you’re going to eat - or you’re talking with your doctor and other healthcare professionals about diet and its impact on disease risks - think a bit more about vitamin D and how much you’re getting. This is particularly true for people with some medical problems, risks, or who are taking certain medications that can interfere with vitamin D’s actions or calcium absorption. But also remember, while increased sun exposure increases your vitamin D, ice cream - although great in the summertime - unfortunately it’s not a great source of vitamin D, and it has lots of fat and calories. So think of it as a treat and not a vitamin D supplement….. Or maybe just think of it as a “supplemental treat.”

A friend wearing a t-shirt from our favorite dairy on a very cloudy day at the beach.

A long-standing debate in the life sciences has been the role of nature versus nurture in determining individual characteristics. For example, how much of an individual’s height is determined by their genes and how much by their nutrition – both in childhood and prenatally?

In the last few decades advances in our understanding of genetics has shifted this dichotomy to describe it in terms of genetics versus environmental factors, and expanded our appreciation for the role nature/genetics play in causing all manner of human diseases. For example, it was discovered that genetically determined slow serotonin transporters in the brain can predispose individuals to developing depression. However, the more we learn about genetics, similarly exciting discoveries are being made into how environmental factors influence the activity of genes, and thus affect an individual’s health.

Thus - like many things with multifactorial causes - the pendulum swings one way and then the other, i.e. between nature/genetics and nurture/environment.

But what has also become clear is that genetics and environmental influences are not  separable - they interact in important ways, and both can cause health problems and be routes to solutions too.

What recently caught my eye in the nature versus nurture debate were two studies about smoking cessation that came out in the last couple of weeks. The first, by Nicholas Christakis published in the New England Journal of Medicine (and reported in the May 22nd New York Times) describes the importance of social factors for people trying to quit smoking. This study demonstrates how an individual’s social environment plays a dramatic role in their ability to stop smoking, and how people can help each other stop smoking as a collective activity.

On the nature side of the equation, NIH researcher George Uhl led a study that shows how genetic markers can predict which of two smoking cessation treatments will be more likely to work for an individual. From these two studies it is also possible to postulate that individuals may have genetic predispositions that effect the ability of social networks to help them to stop smoking – or possibly to start smoking in the first place. (Didn’t we call this peer-pressure in junior high?)

I find both these studies very interesting because for years smoking has often been described in terms of individual choice (or weakness), and as such something that is completely separate from genetic or environmental factors. These studies refute that popular myth, and more generally illustrate the fundamental point that most illnesses and healthcare problems are complex, and that the solutions to these problems need to be similarly sophisticated. This also reminds me why I cringe a bit when someone says to fix a healthcare problem, “all we need to do is…….”

What are your favorite examples of interacting genetic and environmental factors, or where simple solutions have gone awry when used for complex problems?

The Institute of Medicine put out a report yesterday titled “Retooling for an Aging America: Building the Health Care Workforce.” The report discusses how the aging of the baby-boom generation will create greater needs for health care providers (of all types) who are trained in caring for the elderly with chronic conditions. The report’s recommendations fall into three categories: training, system transformation and financing. Like many reports about health system improvement, their recommendations all make sense - particularly within the context of the three categories. However, like many IOM reports, the writing by Committee process is a bit evident in that, (at least from the Executive Summary), it doesn’t seem to describe a complete plan, nor does it prioritize any of its recommendations - either in terms of funding or which actions should be done first.

In addition, while the report recognizes that the elderly in the coming decades will be healthier than those of 20 or 30 years ago, it doesn’t seem to fully address how this will change the healthcare services needed by the future elderly.

It seems to me, that one of the major challenges facing the healthcare system of the future is how to better manage chronic conditions - regardless of the patient’s age. Thus, rather than retrain clinicians (or train more caregivers) in geriatrics, there needs to be more across the board efforts in chronic care management and coordination among all levels of caregivers. This would benefit the growing elderly population - many, but not all of whom will have multiple chronic conditions - as well as the non-elderly with chronic diseases like diabetes, and the many neuromuscular degenerative diseases like MS or rheumatoid arthritis. This type of system-wide transformation seems like a better use of resources than segmental/specialized retraining and recruitment.

What are your thoughts?

Medical information can change how clinicians treat patients, how patients care for themselves, and how healthcare payers promote or prevent the use of treatments and diagnostic tests. However, this information can act as either a broad sword or a scalpel, and produce good or bad outcomes.

A recent report from a Canadian new service about an article from the Canadian Medical Association Journal describing the outcomes from warning about the use of anti-depressants in children brings this issue down from a general concept to being very specific. This news report stated:

Two years after Health Canada warned about prescribing anti-depressants to children, the number of children and teens who died by suicide increased 25 per cent after years of steady decline, major new Canadian research shows.

And the increased suicide rate coincided with a 10-per-cent decrease in the rate of visits to doctors for the treatment of depression in children.

For the study, researchers tracked what happened in Manitoba before and after Health Canada warned in 2004 that newer antidepressants may be associated with an increased risk of “suicide-related” events in patients under 18.

They found the warning was followed by an overall 14-per-cent drop in antidepressant use among children and adolescents, fewer visits to doctors for depression, and - among eight- to 17-year-olds - increased rates of completed suicide.

More than 90 per cent of the children and teens who killed themselves were not taking antidepressants when they died.

Published Tuesday in the journal of the Canadian Medical Association Journal, the study is the first to document “such a wide range of unintended health consequences” from a major drug warning, the authors say.

Lead author Dr. Laurence Katz, a child and adolescent psychiatrist in Winnipeg, warns the increased risk of suicide could be a “random fluctuation.”

“We can’t say the warning, or the change in antidepressant use or the physician office visits caused changes in suicide rates,” says Katz.

The suicide rate among children and teens was also still relatively small, from 0.04 for every 1,000 children and adolescents before the warning, to 0.15 per 1,000 after.

But Katz worries the widely publicized drug warnings have led to more cases of untreated depression, and an impact “beyond what was intended.” The drop in doctors visits for depression suggests that some vulnerable children are getting no treatment, including psychotherapy, at all. He says his hunch is that families were afraid to go to the doctor for fear their child would be put on medication.

“But that’s not the only treatment for depression. Not going to the doctor deprives you of all forms of treatment.”

If anything, researchers expected office visits to go up after the warning was issued because physicians were urged to increase the monitoring of patients for potential adverse reactions.

Katz, an associate professor of psychiatry at the University of Manitoba, says the drug warnings and media response may have “generated a lot of fear.”

“Understandably parents who kept bringing their children, their teenagers in for troubles with depression were already struggling, and fearful (and) often appropriately cautious about whether their child or teenager should be put on a medication.”

Katz believes the findings could be applied to any Canadian jurisdiction. Other studies coming out of the U.S. are showing similar results. [Emphasis added]

The antidepressant warning involved drugs known as SSRIs, or selective serotonin re-uptake inhibitors, a class that includes Prozac, Paxil and Zoloft, as well as serotonin noradrenaline re-uptake inhibitors (SNRIs), which include Effexor. The drugs have not been approved in Canada for children, but doctors have prescribed them “off-label,” which they are legally permitted to do, to tens of thousands of toddlers, children and teens for depression, social phobia, anxiety and obsessive-compulsive disorders.

In 2003 the U.K. banned antidepressants for children. The only exception was Prozac. Studies have shown the drug is safe and effective in children.

A year later, Health Canada warned that people taking the newer-generation antidepressants may experience behaviour or emotional changes that may put them “at increased risk of self-harm or harm to others.”

Katz says he didn’t have a problem with the warnings themselves. But he says some people leaped to the assumption “that these medications lead people to kill themselves.”

[The report also notes that, “For young adults, there was no significant change in the rate of completed suicide.”]

Obviously, the outcomes found in this study are very worrisome, but it also a too dramatic example of the principle of unintended consequences.

It also reminds me of how a news story in the early 1990s about adverse reactions with the second medicine to treat AIDS.  This news report caused many AIDS patients to stop taking the medicine, and given that there was only one other medicine to treat AIDS, this certainly wasn’t a good thing for their long-term survival

Although correlations don’t prove causations, I think this study definitely underscores the importance of healthcare regulators - and their media colleagues - carefully considering how they present new health information and notices to the public - for both good findings or dire warnings. With all the proposals to empower patients to make their own decisions through consumer directed insurance plan, and to give people more health information, there should also be much more research into how people respond to health related information delivered in different forms from various sources.

I’m usually either supportive or neutral about alternative therapies because they generally aren’t harmful, and can be beneficial. However, there seem to be more and more recalls of these products by the Food and Drug Administration (FDA) for mislabelings that are significant, although seemingly not extremely dangerous.

On the other hand, I was struck by a press release I got yesterday from the FDA about a recall for the dietary supplement products “Total Body Formula” and “Total Body Mega Formula.” The recall was because these products had more than 200 times the amount of selenium than was printed on the products’ label – and the press release noted that, “Excessive intake of selenium is known to cause symptoms to include significant hair loss, muscle cramps, diarrhea, joint pain, fatigue, loss of finger nails and blistering skin.”

I guess this is another instance of how too much of something that is normally good, can be, well, not so good. And with 43 adverse reactions reported to the FDA, the recall seems like a very good thing.

UPDATE: The FDA updated their warning and information on this issue this afternoon - click here to see the FDA website notice.

My last post contained some perspectives about fake medicines. That same day, the LA times ran an article about California’s long-delayed pedigree requirements for tracking prescription medicines. This law was prompted by the discovery of fake medicines for HIV/AIDS in 2000, and was intended to achieve what the FDA has been trying to implement for many years.

The LA Times article blames the delays in the state’s drug tracking system on the industry - from the manufacturer to the retail pharmacy. I suspect that the real challenge is not in the technical or cost aspects from the manufacturers - who certainly have lots to gain by stopping counterfeits of their products from being sold instead of the real thing, but from the wholesalers and to a lesser extent the pharmacies.

I’m assuming that wholesalers don’t knowingly sell counterfeit medicines, but under the current system, they can potentially make a lot of money doing so - particularly when buying them allows for a larger mark-up to the pharmacies than the real medicine. This is part of the economic reality of wholesalers, who in effect are arbitraging the differential costs of pharmaceuticals as a commodity by buying someone else’s excess supply and delivering it where it is needed. Now normally this would be market forces working to efficiently delivery medicines to where they were needed. However, without adequate pedigrees (i.e. paper or electronic documentation demonstrating the entire chain of custody of the medicines from the time it left the manufacturer), there is a great economic incentive for counterfeiters to push their fake medicines into this supply chain and make a huge profit.

Of course, the pedigree system needs to be sophisticated enough that it too can’t be forged - otherwise it is worthless. This is why retail pharmacies may be balking at the cost of implementing a system where they aren’t going to benefit, and don’t believe they are part of the problem. In general, pharmacies, don’t have great incentive for selling fake medicines - they would get paid the same dispensing and product fees whether the product was real of fake. The only case where pharmacies would increase their profits is if they were to be able to buy the fake medicines for less, but this would probably only occur for large chain pharmacies where they are essentially acting as their own wholesalers and wouldn’t be the case for the independent pharmacies - the few that are left.

Because pharmaceutical companies have incentive to track shipments of their medicines and make sure they aren’t stolen, some are starting to use RFID technology. This is surely a big investment that is worth the cost. Implementing a secure pedigree tracking system might be more costly, but would certainly be a worthwhile expense to ensure the safety and quality of medical care.

In general health policy people in the US don’t like to talk about counterfeit medicines because it raises the potential that people won’t trust their medical systems or their medicines. That attitude would be OK if there was nothing to be done about it, but since there is a solution, I think it should be talked about. The other challenge to pushing for drug tracking systems is that as health reform initiatives go, it’s not as “sexy” as electronic medical records, checklists, “evidence based medicine” or eliminating fraud and abuse and using the savings to expand insurance coverage to the uninsured. But it is a doable improvement. The challenge is figuring out how to pay for it, and convincing all the stakeholders effected to work together to make it happen.

I’ve been trying to figure out how to write something meaningful about the many reports over the last several months about the safety, costs and quality of medicines. I finally concluded that rather than a too lengthy blog post, a series of snapshots would create a good description of the situation - sort of like a slide show rather than a feature film:

Safety of Generic Drugs: A recent LA Times article discussed patients who had adverse reactions when switched from a brand name to a generic medicine. This article includes physicians’ experiences with several types of generic medicines, e.g. for epilepsy, depression, high blood pressure, irregular heart rhythms, and to prevent rejection of organ transplants. Aside from epilepsy, these are different types of medicines from “narrow-therapeutic-index” (or NTI) medicines which have a small dosage range which produces the desired clinical effects before causing known side-effects. Also, the current safety concerns are not related to what happened in the early 1990s, when some generic companies where caught submitting false safety data — they used the brand name medicine for the bioequivalency testing required by the FDA instead of actually testing their generic versions. (Yes, people went to jail.)

Safety of Medicines Imported into the US: Medicines imported from other countries have raised safety concerns because of lack of quality oversight and the murkiness of the chain of custody. These concerns have recently been highlighted by the contamination problems of herparin from a factory in China, and reminds me of how the head of the Chinese State Food and Drug Administration was convicted last summer of taking bribes in exchange for approving generic drugs that hadn’t had the required testing. (They sentenced him to death, and actually hanged him shortly after he was convicted.)

Fake Medicines: Whether produced in the US or someplace else, there is a growing market in fake medicines. The economic incentives are huge, and unlike illegal recreational drugs, the risk of your customer to violently come after you for selling substandard products is very low. There have been cases of fake medicines made here in the US, and the World Health Organization estimates that up to 30% of medicines in some parts of the world are fake.

Fake antibiotics are of particular concern: Fake antimalarial medicines sometimes contain tylenol or asprin which lowers the malarial fever without actually treating the infection - so people think they are getting better while they continue to spread the infection. And subpar medicines that only contain a fraction of the antibiotic promote the spread of resistant strains of bacteria. So fake or substandard antibiotics may actually be worse than no pills at all.

Even the New York Times editorial board recognized the global dangers of fake medicines in a December 12, 2006 editorial.

Follow-On Biologics: There has been a lot of interest in new versions of biologic treatments. These have many names: generic biologics, biogenerics, biosimilars, and follow-on biologics. One of the great confusions with this issue is that drugs and biologics are different categories of treatments. Because of their different chemical natures they are covered by different parts of US law, and until recently they were regulated by separate divisions of the Food and Drug Administration.

While drugs and biologics are both made up of atoms, drugs are much simpler, generally much more stable, and produced by chemical reactions starting from raw chemical ingredients or from a natural compound purified from a plant or animal source. Biologics on the other hand are much larger compounds (often proteins), and are generally made by living cell cultures (or in some cases whole animals), with the active drug is purified from that source.

The different structural complexities of drugs and biologics is because small molecular drugs are based upon a limited number of configurations of their atoms - usually 1, or 2, or sometimes 4 variations that are either mirror images of each other, or forms that exist in a predictable equilibrium. Biologics on the other hand have 2 or 3 more levels of structural complexity beyond that found in small molecules. (See here for a description of the primary, secondary, tertiary and quaternary structures of proteins.) Printing is a good an analogy to the structure of drugs and biologic, with a drug being like a sentence, where the series of letter and punctuation defines it. Conversely, a biologic is a like a book, where the construction of the paragraphs and chapters are its secondary and tertiary structures, and the footnotes, references, bibliography and appendices are the quaternary structures. Obviously it is easy to copy a sentence to look like the original, but replicating a book, with the same pagination and structure is much more complicated.

As a semi-avid baker, another analogy I like for the difference between drugs and biologics is a comparison between baking powder and eggs. Baking powder is a combination of chemicals designed to produce a chemical reaction to yield the right chemical/baking effect when used in the right amount. It is generally stable, and lasts for a long time when not exposed to air. Eggs on the other hand, can easily spoil (particularly if the shell is cracked), and have two major parts - the yolk and the white. The whites are mostly protein, and yield very different results depending upon how they are used. For example, adding raw egg whites to cake batter produces a very different result than if they are heated first and then added. (Think about the difference between an angle food cake and a quiche.) Egg yolks are mostly fat are are nicely separated from the whites. Mixed with the whites they cook up one way, and separately are used in pudding, custards, etc.

Adverse Drug Events and Medical Errors in Hospitals: There have been many studies about medical errors in hospitals and how many of those relate to adverse drugs events because the patient received the wrong medicine or the wrong amount of the medicine. These studies clearly point out the value of electronic medical records which avoid handwriting mistakes, and can automatically check for drug-drug interactions. Another important organizational feature of hospital care is the integrated medical team that includes experienced pharmacists and nurses. Such teams ensure rapid and accurate communications about treatment issues among the clinicians writing the prescription and those dispensing it or delivering/administering it to the patient.

Conclusions: Medicines are extremely potent, they can be very complex, and they are central to one of the mantras of clinically and cost effective care: “The right treatment, to the right patient, at the right time.” Electronic medical records and electronic prescribing systems certainly can help achieve that goal, while substituting non-identical medications, or enabling the distribution or use of substandard of fake medicines undermines movement towards that goal.

A couple of days a week I work out of shared office space in Cambridge, MA that is part of a multi-floor incubator/start-up facility. One of the benefits in the office is the food stocked in the kitchens - including lots of healthy things, like fresh fruits, nuts, dried fruit, bagels, etc….. Now not all the food is purely healthy…. They have sodas and M&Ms, etc. But today I did a double-take, when I saw that the Drakes Apple FruitPies had 8 grams of Trans Fats per serving.

For those of you not familiar with Trans Fats, they are chemically created by taking naturally occurring oils and heating them in the presence of a metal catalyst (like nickel or platinum) to add extra hydrogens to the oil. This process creates “partially hydrogenated oils” which are solid at room temperature and easier to bake with etc. Chemically modifying the oils also causes the naturally occurring double bonds within the oil’s carbon backbone to rearrange so that the hydrogens on the same side of the carbon chain (see A bel0w), get flipped around so that the hydrogens are on opposite sides (See B below)

A: Cis - Fat  . . . . . .B: Trans-Fat

So why does this matter. Numerous studies have shown that Trans Fats increase blood levels of triglycerides and lower good cholesterol (HDL) — both of which increase risks for cardiovascular disease and death. The biochemical reasons for this are not clear, but it seems to me that Trans Fats are acting like a metabolic poison.

The process that keeps so-called foods that contain Trans Fats from spoiling, is the same that messes up human physiology: In Trans Fat “foods,” microorganisms that normally cause food to spoil can’t digest the trans fats, so the food doesn’t spoil. In the human body, our natural molecular processes for breaking down fats can’t easily “eat” Trans Fats either - so it literally gums up the works. An analogy might be if you put your shoes on the wrong feet and tried to run. You could move, but it would be awkward, inefficient, and sooner or later something connected to your feet would start complaining and eventually break. It’s not that the shoes doen’t look like shoes, but they don’t fit the feet so things don’t work right. Trans fats look like oils (just like the oil in your car looks like oil), but trans fats are not the shape of oils your body’s cells are expecting, so problems arise when they have to deal with them.

Now if you don’t like this situation, (and crave those snack cakes), don’t blame your body’s cells - they didn’t ask for the Trans Fats - you’re the one who decided to eat them - your cells are doing their best to figure out what to do with them. But unfortunately they aren’t equipped to easy break them down - they’d rather have real food, not Trans Fats.