This is a simplified summary of the last two posts.
Polyunsaturated fats in the diet are mostly omega-6 or omega-3. These get converted into a diverse and influential class of signaling molecules in the body called eicosanoids. On their way to becoming eicosanoids, they get elongated. These elongated versions can be measured in tissue, and the higher the proportion of elongated omega-6 in the total pool, the higher the risk of a heart attack.
Eicosanoids are either omega-6 or omega-3-derived. Omega-6 eicosanoids, in general, are very potent and participate in inflammatory processes and blood clotting. Omega-3 eicosanoids are less potent, less inflammatory, less clot-forming, and participate in long-term repair processes. This is a simplification, as there are exceptions, but in a broad sense seems to be true.
In the modern U.S. and most other affluent nations, we eat so much omega-6 (mostly in the form of liquid industrial vegetable oils), and so little omega-3, that we create a very inflammatory and pro-clotting environment, probably contributing to a number of chronic diseases including cardiovascular disease.
There are two ways to stay in balance: reduce omega-6, and increase omega-3. In my opinion, the former is more important than the latter, but only if you can reduce omega-6 to below 4% of calories. If you're above 4%, the only way to reduce your risk is to outcompete the omega-6 with additional omega-3. Keeping omega-6 below 4% and ensuring a modest but regular intake of omega-3, such as from wild-caught fish, will probably substantially reduce the risk of cardiovascular disease and other chronic illnesses.
Bottom line: ditch industrial vegetable oils such as corn, soybean, safflower and sunflower oil, and everything that contains them. This includes most processed foods, especially mayonnaise, grocery store salad dressings, and fried foods. We aren't meant to eat those foods and they derail our metabolism on a fundamental level. I also believe it's a good idea to have a regular source of omega-3, whether it comes from seafood, small doses of cod liver oil, or small doses of flax.
For Those not Scientifically Inclined
This is a simplified summary of the last two posts.
Polyunsaturated fats in the diet are mostly omega-6 or omega-3. These get converted into a diverse and influential class of signaling molecules in the body called eicosanoids. On their way to becoming eicosanoids, they get elongated. These elongated versions can be measured in tissue, and the higher the proportion of elongated omega-6 in the total pool, the higher the risk of a heart attack.
Eicosanoids are either omega-6 or omega-3-derived. Omega-6 eicosanoids, in general, are very potent and participate in inflammatory processes and blood clotting. Omega-3 eicosanoids are less potent, less inflammatory, less clot-forming, and participate in long-term repair processes. This is a simplification, as there are exceptions, but in a broad sense seems to be true.
In the modern U.S. and most other affluent nations, we eat so much omega-6 (mostly in the form of liquid industrial vegetable oils), and so little omega-3, that we create a very inflammatory and pro-clotting environment, probably contributing to a number of chronic diseases including cardiovascular disease.
There are two ways to stay in balance: reduce omega-6, and increase omega-3. In my opinion, the former is more important than the latter, but only if you can reduce omega-6 to below 4% of calories. If you're above 4%, the only way to reduce your risk is to outcompete the omega-6 with additional omega-3. Keeping omega-6 below 4% and ensuring a modest but regular intake of omega-3, such as from wild-caught fish, will probably substantially reduce the risk of cardiovascular disease and other chronic illnesses.
Bottom line: ditch industrial vegetable oils such as corn, soybean, safflower and sunflower oil, and everything that contains them. This includes most processed foods, especially mayonnaise, grocery store salad dressings, and fried foods. We aren't meant to eat those foods and they derail our metabolism on a fundamental level. I also believe it's a good idea to have a regular source of omega-3, whether it comes from seafood, small doses of cod liver oil, or small doses of flax.
Polyunsaturated fats in the diet are mostly omega-6 or omega-3. These get converted into a diverse and influential class of signaling molecules in the body called eicosanoids. On their way to becoming eicosanoids, they get elongated. These elongated versions can be measured in tissue, and the higher the proportion of elongated omega-6 in the total pool, the higher the risk of a heart attack.
Eicosanoids are either omega-6 or omega-3-derived. Omega-6 eicosanoids, in general, are very potent and participate in inflammatory processes and blood clotting. Omega-3 eicosanoids are less potent, less inflammatory, less clot-forming, and participate in long-term repair processes. This is a simplification, as there are exceptions, but in a broad sense seems to be true.
In the modern U.S. and most other affluent nations, we eat so much omega-6 (mostly in the form of liquid industrial vegetable oils), and so little omega-3, that we create a very inflammatory and pro-clotting environment, probably contributing to a number of chronic diseases including cardiovascular disease.
There are two ways to stay in balance: reduce omega-6, and increase omega-3. In my opinion, the former is more important than the latter, but only if you can reduce omega-6 to below 4% of calories. If you're above 4%, the only way to reduce your risk is to outcompete the omega-6 with additional omega-3. Keeping omega-6 below 4% and ensuring a modest but regular intake of omega-3, such as from wild-caught fish, will probably substantially reduce the risk of cardiovascular disease and other chronic illnesses.
Bottom line: ditch industrial vegetable oils such as corn, soybean, safflower and sunflower oil, and everything that contains them. This includes most processed foods, especially mayonnaise, grocery store salad dressings, and fried foods. We aren't meant to eat those foods and they derail our metabolism on a fundamental level. I also believe it's a good idea to have a regular source of omega-3, whether it comes from seafood, small doses of cod liver oil, or small doses of flax.
More Documents About the Selling of Seroquel Show How Research Was "Subordinated to Commercial Goals"
We posted earlier this year about how documents produced on discovery and recently unsealed during litigation suggested how AstraZeneca handled clinical research data in the marketing of its atypical anti-psychotic drug Seroquel (quetiapine). A new crop of documents has just been released, providing yet more insights, as reported by the St Petersburg (Florida) Times:
In particular,
This is a reminder how beleaguered we advocates of evidence-based health care (EBHC) have become. The idea of EBHC was that health care decisions for individual patients, and policies for groups of patients ought to be guided by critical review of the best available evidence from clinical research, guided by knowledge of biology and the biopsychosocial context of health, and informed by patients' values and preferences. The idea still makes sense to me, but it only works if physicians, patients and policy-makers have access to an unbiased sample of clinical research studies, so that studies with are not selectively suppressed to support vested interests. Although critical review can account for inevitable trade-offs, compromises, and errors in how studies are designed, implemented, and analyzed, the clinical epidemiological methods it uses are really not designed to root out falsehoods and deliberate deception.
However, the ongoing story of Seroquel, and many other cases discussed on Health Care Renewal suggest that when clinical research is sponsored by those who can profit from the product or service it evaluates, that research is prone to suppression and manipulation. Although I believe there are many honest scientists who work for pharmaceutical, biotechnology, device, health information technology and other health care corporations, it seems they often have to answer to marketers whose only goal is to sell more product.
As long as clinical research is sponsored and run by the people who can profit directly from selling the products and services the research is meant to evaluate, the ideal of evidence-based health care becomes less attainable.
As we have said before, suppression and manipulation of research amounts to post-hoc abuse of research subjects who volunteered their participation believing that it would advance science and health care.
Furthermore, suppression and manipulation of research can deceive physicians into prescribing tests and treatments that will fail to help, or even harm patients, and deceive patients into thinking that they are getting the best possible tests and treatments, when, again what they are getting is ineffective or even harmful.
In my humble opinion, there is an increasingly strong argument that clinical research should not be controlled, and probably should not be done at all by organizations with vested interests in the research producing results favorable to their products.
Behind the scenes at the global pharmaceutical company AstraZeneca, the team in charge of the blockbuster antipsychotic Seroquel had one mission: make the multibillion-dollar seller even bigger.
To that end, internal company documents released Wednesday show how the British drugmaker hid unfavorable study results, promoted unapproved uses and even considered pitching the drug as less likely to lead to suicidal thinking than competitors'.
In particular,
Documents suggest Seroquel studies were repeatedly subordinated to commercial goals.
When a study in 2002 failed to show that Seroquel's sustained release formula was any more effective than a placebo in treating schizophrenia, orders from the top were to keep the results 'in strictest confidence.'
When a scientist in England wanted to study the weight gain in rats on Seroquel, AstraZeneca declined to fund the research, saying 'we could wind up with results that are not clearly advantageous.'
In one discussion, it was suggested that authors of potentially helpful research reports who raised too many questions, slowing publication, should be asked to step down.
A researcher who pressed for results of an unfavorable trial was rebuffed for weeks before being given 'three or four sentences describing high-level results.'
AstraZeneca marketers were jealous of what they saw as competitor Lilly's ability to cast questionable study results in a positive light. 'They (Lilly) are able to spin the same data in many different ways through an effective publications team,' according to a 2003 memo. 'Negative data usually remains well hidden.'
As Seroquel's sales soared, documents reflect an ongoing struggle between the safety and marketing teams over the potentially damaging issue of weight gain. In 2000, the company's scientists said data did not support the marketing claim that Seroquel resulted in only 'limited' weight gain. Close to 23 percent of the people who took the drug gained more than 7 percent.
Despite the safety team's objections, the word 'limited' remained on Seroquel's label for two more years.
This is a reminder how beleaguered we advocates of evidence-based health care (EBHC) have become. The idea of EBHC was that health care decisions for individual patients, and policies for groups of patients ought to be guided by critical review of the best available evidence from clinical research, guided by knowledge of biology and the biopsychosocial context of health, and informed by patients' values and preferences. The idea still makes sense to me, but it only works if physicians, patients and policy-makers have access to an unbiased sample of clinical research studies, so that studies with are not selectively suppressed to support vested interests. Although critical review can account for inevitable trade-offs, compromises, and errors in how studies are designed, implemented, and analyzed, the clinical epidemiological methods it uses are really not designed to root out falsehoods and deliberate deception.
However, the ongoing story of Seroquel, and many other cases discussed on Health Care Renewal suggest that when clinical research is sponsored by those who can profit from the product or service it evaluates, that research is prone to suppression and manipulation. Although I believe there are many honest scientists who work for pharmaceutical, biotechnology, device, health information technology and other health care corporations, it seems they often have to answer to marketers whose only goal is to sell more product.
As long as clinical research is sponsored and run by the people who can profit directly from selling the products and services the research is meant to evaluate, the ideal of evidence-based health care becomes less attainable.
As we have said before, suppression and manipulation of research amounts to post-hoc abuse of research subjects who volunteered their participation believing that it would advance science and health care.
Furthermore, suppression and manipulation of research can deceive physicians into prescribing tests and treatments that will fail to help, or even harm patients, and deceive patients into thinking that they are getting the best possible tests and treatments, when, again what they are getting is ineffective or even harmful.
In my humble opinion, there is an increasingly strong argument that clinical research should not be controlled, and probably should not be done at all by organizations with vested interests in the research producing results favorable to their products.
Sanofi-Aventis Settles
Here is another addition to the parade of multi-million dollar legal settlements by health care corporations. As reported by the AP:
It seems that scarcely a week goes by without a settlement of charges of unethical behavior by some major health care organization. The ongoing parade of such cases ought to inspire some worry about the ethics of the leaders of such organization. Given the current very public discussion of how expensive health care has become, one would think that there would be some discussion of how much of this expense is due to various kinds of deceptive and unethical behavior by some of the biggest, richest, and most powerful health care organizations. But perhaps that would be too upsetting for those who make so much money running these organizations.
As we have said before, most recently here, while human beings authorized or committed the acts that got the organization in trouble, rarely do these people seem to suffer any negative consequences. At most, the organization may pay a fine. In this case, the fine was, in corporate terms, of modest size. However, even a large fine, may come out of dividends or the stock price, dispersing the cost to stock-holders, or out of salaries across the board, dispersing the cost to all employees. Thus, those who got the organization into trouble are unlikely to feel pain from it. Perhaps because of reverence for all organizations related to health care, and fear that the bankruptcy of any health care organization will leave patients in the lurch, prosecutors do not seem inclined to actually prosecute such organizations. The net effect, though, seems to be that dishonest executives of health care organizations can continue to act with impunity.Until bad leadership of health care organizations leads to negative consequences for those practicing it, health care leadership can be expected to continuously degrade.
ADDENDUM (2 June, 2009) - See these comments on the Effect Measure blog.
Drugmaker Sanofi-Aventis has agreed to pay nearly $100 million to settle allegations it cheated Medicaid on the cost of nasal sprays.
The Justice Department said Aventis Pharmaceutical Inc., a wholly owned subsidiary of Sanofi-Aventis U.S. LLC, has agreed to pay the government $95.5 million to settle the charges.
The government charged that between 1995 and 2000, Aventis and its corporate predecessors did not offer Medicaid the best prices for the sprays Azmacort, Nasacort and Nasacort AQ.
In reaching the settlement, Sanofi-Aventis U.S. did not admit any wrongdoing. The company, based in Bridgewater, N.J., issued a statement saying it believed the old pricing system was legal.
Under the law, the company was required to tell Medicaid the lowest price that it charged companies for those products, and offer state Medicaid programs rebates based on those prices.
Prosecutors contend that in order to dodge that obligation, Aventis entered into a private deal with the HMO Kaiser Permanente that repackaged Aventis drugs under a new label, allowing them to overcharge Medicaid programs for the same product.
It seems that scarcely a week goes by without a settlement of charges of unethical behavior by some major health care organization. The ongoing parade of such cases ought to inspire some worry about the ethics of the leaders of such organization. Given the current very public discussion of how expensive health care has become, one would think that there would be some discussion of how much of this expense is due to various kinds of deceptive and unethical behavior by some of the biggest, richest, and most powerful health care organizations. But perhaps that would be too upsetting for those who make so much money running these organizations.
As we have said before, most recently here, while human beings authorized or committed the acts that got the organization in trouble, rarely do these people seem to suffer any negative consequences. At most, the organization may pay a fine. In this case, the fine was, in corporate terms, of modest size. However, even a large fine, may come out of dividends or the stock price, dispersing the cost to stock-holders, or out of salaries across the board, dispersing the cost to all employees. Thus, those who got the organization into trouble are unlikely to feel pain from it. Perhaps because of reverence for all organizations related to health care, and fear that the bankruptcy of any health care organization will leave patients in the lurch, prosecutors do not seem inclined to actually prosecute such organizations. The net effect, though, seems to be that dishonest executives of health care organizations can continue to act with impunity.Until bad leadership of health care organizations leads to negative consequences for those practicing it, health care leadership can be expected to continuously degrade.
ADDENDUM (2 June, 2009) - See these comments on the Effect Measure blog.
Canadian Health IT Ripoff ... Is Anyone in the U.S. Paying Attention?
In my Feb. 18, 2009 Wall Street Journal letter to the editor I wrote:
The Toronto Sun article concluded with this:
I reiterate, I hope patients in the U.S. actually get something for the $20+ billion we're about to spend to force health IT down doctors' throats.
-- SS
You observe that the true political goal is socialized medicine facilitated by health care information technology. You note that the public is being deceived, as the rules behind this takeover were stealthily inserted in the stimulus bill.Regarding my fears about waste and about the identity of the true beneficiaries, this in from the Toronto Sun in Canada:
I have a different view on who is deceiving whom. In fact, it is the government that has been deceived by the HIT industry and its pundits. Stated directly, the administration is deluded about the true difficulty of making large-scale health IT work. The beneficiaries will largely be the IT industry and IT management consultants.
For £12.7 billion the U.K., which already has socialized medicine, still does not have a working national HIT system, but instead has a major IT quagmire, some of it caused by U.S. HIT vendors.
HIT (with a few exceptions) is largely a disaster. I'm far more concerned about a mega-expensive IT misadventure than an IT-empowered takeover of medicine.
The stimulus bill, to its credit, recognizes the need for research on improving HIT. However this is a tool to facilitate clinical care, not a cybernetic miracle to revolutionize medicine. The government has bought the IT magic bullet exuberance hook, line and sinker.
I can only hope patients get something worthwhile for the $20 billion.
I stand by my Wall Street Journal letter, to the letter.eHealth making critics sick
Opposition wants 'walking papers' issued to minister, CEO over questionable expenditures
eNough, government critics say.
Opposition parties at Queen's Park are calling for heads to roll after the newest revelations of eye-popping expenditures at eHealth Ontario -- the taxpayer-funded agency established to produce electronic medical records for every citizen in the province.
One consultant with a four-month contract worth $210,600 billed taxpayers for items as small as her $1.57 Tim Hortons tea, her BBQ chicken sub, a $2.98 soup, and her muffins and pops, as well as travel to and from Alberta, and a $2,820-a-month apartment in Toronto.
Even Premier Dalton McGuinty is struggling to understand the spending and has said that he welcomes the results of an ongoing investigation of the agency by the auditor general.
... Freedom of Information documents obtained by the Progressive Conservatives have revealed that eHealth Ontario CEO Sarah Kramer approved nearly $5 million in contracts that weren't put out for a competitive bid.
Sun Media has learned that one consultant charged taxpayers $300 an hour to consult with her husband -- who also had a consulting contract with eHealth Ontario.
Taxpayers paid $7,000 to a consultant to write Kramer's speech to Health Active 2008, and hundreds of dollars more to update her biography.
Even the official spokesman for eHealth was a consultant who charged $1,600 a day to provide communications advice and talk to media, billing $33,200 for 20.75 days work in March alone.
Questions were also raised in the legislature about consultants who billed the Ontario taxpayer to read The New York Times, talk on the subway and watch TV.
On top of that, Kramer received a $114,000 bonus within months of beginning her $380,000-a-year position.
eHealth Ontario and its predecessor agency have spent $146 million on consultants since 2003, despite commitments to reign in billings for outside expertise, and overall agency spending has ballooned to $839 million.
Other provinces are ahead of Ontario in producing records although so far they have spent less money.
... During Question Period, Runciman called on the premier to give Kramer and Caplan their "walking papers."
The Toronto Sun article concluded with this:
NDP MPP France Gelinas also called for heads to roll, saying eHealth Ontario and its predecessor agency have produced next to nothing for more than three-quarters of a billion dollars.
I reiterate, I hope patients in the U.S. actually get something for the $20+ billion we're about to spend to force health IT down doctors' throats.
-- SS
Eicosanoids and Ischemic Heart Disease, Part II
Here's where it gets more complicated and more interesting. The ratio of omega-6 to omega-3 matters, but so does the total amount of each. This is a graph from a 1992 paper by Dr. Lands:
Allow me to explain. These lines are based on values predicted by a formula developed by Dr. Lands that determines the proportion of omega-6 in tissue HUFA (highly unsaturated fatty acids; includes 20- to 22-carbon omega-6 and omega-3 fats), based on dietary intake of omega-6 and omega-3 fats. This formula seems to be quite accurate, and has been validated both in rodents and humans. As a tissue's arachidonic acid content increases, its EPA and DHA content decreases proportionally.
On the Y-axis (vertical), we have the proportion of omega-6 HUFA in tissue. On the X-axis (horizontal), we have the proportion of omega-6 in the diet as a percentage of energy. Each line represents the relationship between dietary omega-6 and tissue HUFA at a given level of dietary omega-3.
Let's start at the top. The first line is the predicted proportion of omega-6 HUFA in the tissue of a person eating virtually no omega-3. You can see that it maxes out around 4% of calories from omega-6, but it can actually be fairly low if omega-6 is kept very low. The next line down is what happens when your omega-3 intake is 0.1% of calories. You can see that the proportion of omega-6 HUFA is lower than the curve above it at all omega-6 intakes, but it still maxes out around 4% omega-6. As omega-3 intake increases, the proportion of omega-6 HUFA decreases at all levels of dietary omega-6 because it has to compete with omega-3 HUFA for space in the membrane.
In the U.S., we get a small proportion of our calories from omega-3. The horizontal line marks our average tissue HUFA composition, which is about 75% omega-6. We get more than 7% of our calories from omega-6. This means our tissue contains nearly the maximum proportion of omega-6 HUFA, creating a potently inflammatory and thrombotic environment! This is a very significant fact, because it explains three major observations:
But the trend didn't continue into later trials. This makes perfect sense in light of the rising omega-6 intake over the course of the 20th century in the U.S. and other affluent nations. Once our omega-6 intake crossed the 4% threshold, more omega-6 had very little effect on the proportion of omega-6 HUFA in tissue. This may be why some of the very first PUFA diet trials caused increased mortality: there was a proportion of the population that was still getting less than 4% omega-6 in its regular diet at that time. By the 1980s, virtually everyone in the U.S. (and many other affluent nations) was eating more than 4% omega-6, and thus adding more did not significantly affect tissue HUFA or heart attack mortality.
If omega-3 intake is low, whether omega-6 intake is 5% or 10% doesn't matter much for heart disease. At that point, the only way to reduce tissue HUFA without cutting back on omega-6 consumption is to outcompete it with additional omega-3. That's what the Japanese do, and it's also what happened in several clinical trials including the DART trial.
This neatly explains why the French, Japanese and Kitavans have low rates of ischemic heart disease, despite the prevalence of smoking cigarettes in all three cultures. The French diet traditionally focuses on animal fats, eschews industrial vegetable oils, and includes seafood. They eat less omega-6 and more omega-3 than Americans. They have the lowest heart attack mortality rate of any affluent Western nation. The Japanese are known for their high intake of seafood. They also eat less omega-6 than Americans. They have the lowest heart attack death rate of any affluent nation. The traditional Kitavan diet contains very little omega-6 (probably less than 1% of calories), and a significant amount of omega-3 from seafood (about one teaspoon of fish fat per day). They have an undetectable incidence of heart attack and stroke.
In sum, this suggests that an effective way to avoid a heart attack is to reduce omega-6 consumption and ensure an adequate source of omega-3. The lower the omega-6, the less the omega-3 matters. This is a nice theory, but where's the direct evidence? In the next post, I'll discuss the controlled trial that proved this concept once and for all: the Lyon diet-heart trial.
Allow me to explain. These lines are based on values predicted by a formula developed by Dr. Lands that determines the proportion of omega-6 in tissue HUFA (highly unsaturated fatty acids; includes 20- to 22-carbon omega-6 and omega-3 fats), based on dietary intake of omega-6 and omega-3 fats. This formula seems to be quite accurate, and has been validated both in rodents and humans. As a tissue's arachidonic acid content increases, its EPA and DHA content decreases proportionally.On the Y-axis (vertical), we have the proportion of omega-6 HUFA in tissue. On the X-axis (horizontal), we have the proportion of omega-6 in the diet as a percentage of energy. Each line represents the relationship between dietary omega-6 and tissue HUFA at a given level of dietary omega-3.
Let's start at the top. The first line is the predicted proportion of omega-6 HUFA in the tissue of a person eating virtually no omega-3. You can see that it maxes out around 4% of calories from omega-6, but it can actually be fairly low if omega-6 is kept very low. The next line down is what happens when your omega-3 intake is 0.1% of calories. You can see that the proportion of omega-6 HUFA is lower than the curve above it at all omega-6 intakes, but it still maxes out around 4% omega-6. As omega-3 intake increases, the proportion of omega-6 HUFA decreases at all levels of dietary omega-6 because it has to compete with omega-3 HUFA for space in the membrane.
In the U.S., we get a small proportion of our calories from omega-3. The horizontal line marks our average tissue HUFA composition, which is about 75% omega-6. We get more than 7% of our calories from omega-6. This means our tissue contains nearly the maximum proportion of omega-6 HUFA, creating a potently inflammatory and thrombotic environment! This is a very significant fact, because it explains three major observations:
- The U.S has a very high rate of heart attack mortality.
- Recent diet trials in which saturated fat was replaced with omega-6-rich vegetable oils didn't cause an increase in mortality, although some of the very first trials in the 1960s did.
- Diet trials that increased omega-3 decreased mortality.
But the trend didn't continue into later trials. This makes perfect sense in light of the rising omega-6 intake over the course of the 20th century in the U.S. and other affluent nations. Once our omega-6 intake crossed the 4% threshold, more omega-6 had very little effect on the proportion of omega-6 HUFA in tissue. This may be why some of the very first PUFA diet trials caused increased mortality: there was a proportion of the population that was still getting less than 4% omega-6 in its regular diet at that time. By the 1980s, virtually everyone in the U.S. (and many other affluent nations) was eating more than 4% omega-6, and thus adding more did not significantly affect tissue HUFA or heart attack mortality.
If omega-3 intake is low, whether omega-6 intake is 5% or 10% doesn't matter much for heart disease. At that point, the only way to reduce tissue HUFA without cutting back on omega-6 consumption is to outcompete it with additional omega-3. That's what the Japanese do, and it's also what happened in several clinical trials including the DART trial.
This neatly explains why the French, Japanese and Kitavans have low rates of ischemic heart disease, despite the prevalence of smoking cigarettes in all three cultures. The French diet traditionally focuses on animal fats, eschews industrial vegetable oils, and includes seafood. They eat less omega-6 and more omega-3 than Americans. They have the lowest heart attack mortality rate of any affluent Western nation. The Japanese are known for their high intake of seafood. They also eat less omega-6 than Americans. They have the lowest heart attack death rate of any affluent nation. The traditional Kitavan diet contains very little omega-6 (probably less than 1% of calories), and a significant amount of omega-3 from seafood (about one teaspoon of fish fat per day). They have an undetectable incidence of heart attack and stroke.
In sum, this suggests that an effective way to avoid a heart attack is to reduce omega-6 consumption and ensure an adequate source of omega-3. The lower the omega-6, the less the omega-3 matters. This is a nice theory, but where's the direct evidence? In the next post, I'll discuss the controlled trial that proved this concept once and for all: the Lyon diet-heart trial.
Eicosanoids and Ischemic Heart Disease, Part II
Here's where it gets more complicated and more interesting. The ratio of omega-6 to omega-3 matters, but so does the total amount of each. This is a graph from a 1992 paper by Dr. Lands:
Allow me to explain. These lines are based on values predicted by a formula developed by Dr. Lands that determines the proportion of omega-6 in tissue HUFA (highly unsaturated fatty acids; includes 20- to 22-carbon omega-6 and omega-3 fats), based on dietary intake of omega-6 and omega-3 fats. This formula seems to be quite accurate, and has been validated both in rodents and humans. As a tissue's arachidonic acid content increases, its EPA and DHA content decreases proportionally.
On the Y-axis (vertical), we have the proportion of omega-6 HUFA in tissue. On the X-axis (horizontal), we have the proportion of omega-6 in the diet as a percentage of energy. Each line represents the relationship between dietary omega-6 and tissue HUFA at a given level of dietary omega-3.
Let's start at the top. The first line is the predicted proportion of omega-6 HUFA in the tissue of a person eating virtually no omega-3. You can see that it maxes out around 4% of calories from omega-6, but it can actually be fairly low if omega-6 is kept very low. The next line down is what happens when your omega-3 intake is 0.1% of calories. You can see that the proportion of omega-6 HUFA is lower than the curve above it at all omega-6 intakes, but it still maxes out around 4% omega-6. As omega-3 intake increases, the proportion of omega-6 HUFA decreases at all levels of dietary omega-6 because it has to compete with omega-3 HUFA for space in the membrane.
In the U.S., we get a small proportion of our calories from omega-3. The horizontal line marks our average tissue HUFA composition, which is about 75% omega-6. We get more than 7% of our calories from omega-6. This means our tissue contains nearly the maximum proportion of omega-6 HUFA, creating a potently inflammatory and thrombotic environment! This is a very significant fact, because it explains three major observations:
But the trend didn't continue into later trials. This makes perfect sense in light of the rising omega-6 intake over the course of the 20th century in the U.S. and other affluent nations. Once our omega-6 intake crossed the 4% threshold, more omega-6 had very little effect on the proportion of omega-6 HUFA in tissue. This may be why some of the very first PUFA diet trials caused increased mortality: there was a proportion of the population that was still getting less than 4% omega-6 in its regular diet at that time. By the 1980s, virtually everyone in the U.S. (and many other affluent nations) was eating more than 4% omega-6, and thus adding more did not significantly affect tissue HUFA or heart attack mortality.
If omega-3 intake is low, whether omega-6 intake is 5% or 10% doesn't matter much for heart disease. At that point, the only way to reduce tissue HUFA without cutting back on omega-6 consumption is to outcompete it with additional omega-3. That's what the Japanese do, and it's also what happened in several clinical trials including the DART trial.
This neatly explains why the French, Japanese and Kitavans have low rates of ischemic heart disease, despite the prevalence of smoking cigarettes in all three cultures. The French diet traditionally focuses on animal fats, eschews industrial vegetable oils, and includes seafood. They eat less omega-6 and more omega-3 than Americans. They have the lowest heart attack mortality rate of any affluent Western nation. The Japanese are known for their high intake of seafood. They also eat less omega-6 than Americans. They have the lowest heart attack death rate of any affluent nation. The traditional Kitavan diet contains very little omega-6 (probably less than 1% of calories), and a significant amount of omega-3 from seafood (about one teaspoon of fish fat per day). They have an undetectable incidence of heart attack and stroke.
In sum, this suggests that an effective way to avoid a heart attack is to reduce omega-6 consumption and ensure an adequate source of omega-3. The lower the omega-6, the less the omega-3 matters. This is a nice theory, but where's the direct evidence? In the next post, I'll discuss the controlled trial that proved this concept once and for all: the Lyon diet-heart trial.
Allow me to explain. These lines are based on values predicted by a formula developed by Dr. Lands that determines the proportion of omega-6 in tissue HUFA (highly unsaturated fatty acids; includes 20- to 22-carbon omega-6 and omega-3 fats), based on dietary intake of omega-6 and omega-3 fats. This formula seems to be quite accurate, and has been validated both in rodents and humans. As a tissue's arachidonic acid content increases, its EPA and DHA content decreases proportionally.On the Y-axis (vertical), we have the proportion of omega-6 HUFA in tissue. On the X-axis (horizontal), we have the proportion of omega-6 in the diet as a percentage of energy. Each line represents the relationship between dietary omega-6 and tissue HUFA at a given level of dietary omega-3.
Let's start at the top. The first line is the predicted proportion of omega-6 HUFA in the tissue of a person eating virtually no omega-3. You can see that it maxes out around 4% of calories from omega-6, but it can actually be fairly low if omega-6 is kept very low. The next line down is what happens when your omega-3 intake is 0.1% of calories. You can see that the proportion of omega-6 HUFA is lower than the curve above it at all omega-6 intakes, but it still maxes out around 4% omega-6. As omega-3 intake increases, the proportion of omega-6 HUFA decreases at all levels of dietary omega-6 because it has to compete with omega-3 HUFA for space in the membrane.
In the U.S., we get a small proportion of our calories from omega-3. The horizontal line marks our average tissue HUFA composition, which is about 75% omega-6. We get more than 7% of our calories from omega-6. This means our tissue contains nearly the maximum proportion of omega-6 HUFA, creating a potently inflammatory and thrombotic environment! This is a very significant fact, because it explains three major observations:
- The U.S has a very high rate of heart attack mortality.
- Recent diet trials in which saturated fat was replaced with omega-6-rich vegetable oils didn't cause an increase in mortality, although some of the very first trials in the 1960s did.
- Diet trials that increased omega-3 decreased mortality.
But the trend didn't continue into later trials. This makes perfect sense in light of the rising omega-6 intake over the course of the 20th century in the U.S. and other affluent nations. Once our omega-6 intake crossed the 4% threshold, more omega-6 had very little effect on the proportion of omega-6 HUFA in tissue. This may be why some of the very first PUFA diet trials caused increased mortality: there was a proportion of the population that was still getting less than 4% omega-6 in its regular diet at that time. By the 1980s, virtually everyone in the U.S. (and many other affluent nations) was eating more than 4% omega-6, and thus adding more did not significantly affect tissue HUFA or heart attack mortality.
If omega-3 intake is low, whether omega-6 intake is 5% or 10% doesn't matter much for heart disease. At that point, the only way to reduce tissue HUFA without cutting back on omega-6 consumption is to outcompete it with additional omega-3. That's what the Japanese do, and it's also what happened in several clinical trials including the DART trial.
This neatly explains why the French, Japanese and Kitavans have low rates of ischemic heart disease, despite the prevalence of smoking cigarettes in all three cultures. The French diet traditionally focuses on animal fats, eschews industrial vegetable oils, and includes seafood. They eat less omega-6 and more omega-3 than Americans. They have the lowest heart attack mortality rate of any affluent Western nation. The Japanese are known for their high intake of seafood. They also eat less omega-6 than Americans. They have the lowest heart attack death rate of any affluent nation. The traditional Kitavan diet contains very little omega-6 (probably less than 1% of calories), and a significant amount of omega-3 from seafood (about one teaspoon of fish fat per day). They have an undetectable incidence of heart attack and stroke.
In sum, this suggests that an effective way to avoid a heart attack is to reduce omega-6 consumption and ensure an adequate source of omega-3. The lower the omega-6, the less the omega-3 matters. This is a nice theory, but where's the direct evidence? In the next post, I'll discuss the controlled trial that proved this concept once and for all: the Lyon diet-heart trial.
Harvard's EMR Justification: We Just Have To Do Something?
I think what I termed "irrational exuberance" over health IT is now devolving into just simple irrationality.
I am unfamiliar with the reasoning employed below (in boldface) by the Harvard researcher, Ashish Jha, MD, MPH (who authored the April 2009 EHR usage survey "Use of Electronic Health Records in U.S. Hospitals" in the NEJM).
From "Cash for Computers", HealthLeaders Media, May 11, 2009. First, my opinions:
Then, Jha's:
$20+ billion and penalties upon already squeezed practitioners and hospitals for non-adoption of expensive, experimental technology is a lot of "doing something.", especially at a time when many are medically uninsured or underserved.
I am also not sure about what point critics are "missing." (Note: I am not a critic, but am a gadfly of healthcare IT mis-design, mismanagement and fraud.)
It appears that reasoning at Harvard has dropped to the level of "we should do it, because we have to do something." Good intentions trump outcomes. Not to make a comparison between HIT and other types of medical experimentation, but it's likely the PI's of the Tuskegee Experiment felt the same way.
Ironically, Harvard is home to Medical Informatics pioneers such as Dr. Octo Barnett, coauthor of the National Research Council report warning that approaches to today's HIT are inadequate.
-- SS
I am unfamiliar with the reasoning employed below (in boldface) by the Harvard researcher, Ashish Jha, MD, MPH (who authored the April 2009 EHR usage survey "Use of Electronic Health Records in U.S. Hospitals" in the NEJM).
From "Cash for Computers", HealthLeaders Media, May 11, 2009. First, my opinions:
... "This forced timeline [by 2014] is a very bad thing. I'm concerned it is going to take an experimental technology and turn it into a train wreck," Silverstein [me - ed.] says. "We need a more gradual process where we can learn from mistakes on a small scale to avoid reproducing them on a large scale ... So now, Silverstein says, healthcare providers are caught between their mission to provide quality care and the financial pressure to install an unproven technology that may threaten the mission.
"Health IT, when it's done correctly, can improve healthcare and reduce costs. But health IT when it is not done well has the exact reverse potential," Silverstein says. "It can impair healthcare, decrease quality, and create other adverse effects for patients. That is the missing element in this discussion."
Then, Jha's:
A need to act
Others aren't so pessimistic. Jha [Ashish Jha, MD, MPH, the lead author of the survey, and an associate professor of health policy and management at Harvard] says hospitals will have five years to establish EHR before federal penalties kick in. And because it involves the federal government, Jha says it's more than likely that those deadlines will get pushed back even further [not according to ONC chair and fellow Harvard professor David Blumenthal, who as I noted in this post said HIT timelines were "cemented in law" - ed.]
Jha says critics are "missing the point."
"I'm not suggesting EHR is going to be a panacea, but the one thing that is absolutely true is there is nothing else out there now that has any more political appeal," Jha says. "Everybody agrees, whether you are a conservative, moderate, or liberal, that we have to do something about healthcare. So the one place where we can all come to agreement is we have to do something about electronic records."
$20+ billion and penalties upon already squeezed practitioners and hospitals for non-adoption of expensive, experimental technology is a lot of "doing something.", especially at a time when many are medically uninsured or underserved.
I am also not sure about what point critics are "missing." (Note: I am not a critic, but am a gadfly of healthcare IT mis-design, mismanagement and fraud.)
It appears that reasoning at Harvard has dropped to the level of "we should do it, because we have to do something." Good intentions trump outcomes. Not to make a comparison between HIT and other types of medical experimentation, but it's likely the PI's of the Tuskegee Experiment felt the same way.
Ironically, Harvard is home to Medical Informatics pioneers such as Dr. Octo Barnett, coauthor of the National Research Council report warning that approaches to today's HIT are inadequate.
-- SS
Health IT Failure Never Puts Patients at Risk
At "Dangerous Health IT Mismanagement, Spin Control and the World's Longest Teething Pains" I commented that executives always find that "patient safety is not compromised" when health IT malfunctions.
Here's another hair-raising story from Down Under. Just a wee glitch:
Move along, nothing to see here. Patients were not put at risk. Who needs regulation? It would only stifle innovation.
-- SS
Here's another hair-raising story from Down Under. Just a wee glitch:
Power failure lasting 36 hours cripples hospital care
By Kate Benson
healthcareitaustralia.blogspot.com
DOCTORS at more than 100 hospitals in the state could not access patient records or vital test results for up to 36 hours last weekend after a power failure crippled NSW Health's computerised database.
Some records were lost, X-ray and pathology results could not be accessed and staff were forced to use whiteboards to keep track of emergency patients after the main server shut down at 9am on Saturday because of a faulty circuit-breaker.
Back-up power from the Cumberland Data Centre, which provides computer access to the Greater Western, Greater Southern and Sydney West area health services also failed, plunging some of the busiest hospitals in the state into chaos.
Thousands of patients were affected, with doctors and nurses forced to take notes on paper and go to other parts of the hospital to collect hard copies of results, extending treatment times and adding to the confusion.
Some staff, who did not want to be named, said the weekend was chaotic and a shambles. One surgeon said it was fortunate no lives were lost.
The chief executive of Sydney West Area Health Service, Steven Boyages, said hospital blackouts that lasted more than 30 to 60 minutes were unacceptable, but the Health Minister, John Della Bosca, insisted patients were not put at risk. "At no time was there any threat to patient care or safety," he said yesterday.
The Opposition spokeswoman on health, Jillian Skinner, said the blackout was "a serious failure" with great potential for disaster.
"Hospitals affected not only lost access to patient records, some lost some patient records altogether … and couldn't access X-rays unless they physically went to the X-ray department for a film copy," she said. "John Della Bosca should explain why the patient records system lost power, why back-up systems also failed, and whether patient safety was compromised."
A spokesman for Mr Della Bosca said workers doing routine maintenance at the data centre had triggered the outage. No patients had reported problems connected to the blackout but a full investigation would be launched. "If necessary changes will be implemented to prevent a recurrence," he said.
with Louise Hall
BLACKED OUT
Hospitals at Westmead, Auburn, Blacktown, Nepean, Lithgow, Mount Druitt, Cumberland, Blue Mountains, Dubbo, Bathurst, Orange, Mudgee, Parkes, Bourke, Albury, Queanbeyan and Goulburn were affected.
Move along, nothing to see here. Patients were not put at risk. Who needs regulation? It would only stifle innovation.
-- SS
The FDA Commissioner Divests
Dr Margaret Hamburg, having been confirmed by the US Senate, is the new commissioner of the US Food and Drug Administration (FDA). We posted twice about whether her and her family's financial relationships might be relevant to her nomination.
Here we discussed her position on the board of directors of Henry Schein, Inc a medical supply company. My concern was whether someone who had spent years being ultimately responsible for maximizing the profits of a medical supply company would be able to be a fair, and when necessary, tough regulator of the companies that supply Henry Schein with products to sell.
Here we discussed Dr Hamburg's husband's leadership of the hedge fund management company, Renaissance Technologies. My concern was whether someone who is part of a family that had gotten rich from buying and selling stocks and financial instruments, of which a likely substantial but unknown fraction were of health care corporations, would again be able to be a fair, and when necessary tough regulator of some of these same companies.
At the time, it did not seem that anyone else shared these concerns. As far as I could tell, there was no discussion of them in the press, or at Dr Hamburg's confirmation hearings.
However, today the Wall Street Journal reported:
So it appears, in retrospect, that the Government Ethics Office also felt that Dr Hamburg's position on the Henry Schein Inc board constituted a conflict of interest. Furthermore, the Office felt that Dr Hamburg's and Mr Brown's holdings in several hedge funds constituted conflicts of interest. So, in retrospect, it is odd that these financial relationships attracted no attention other than that of Health Care Renewal prior to Dr Hamburg's confirmation by the Senate. I do hope that now, having severed significant relationships and sold financial holdings, Dr Hamburg will prove to be a fair, and tough when necessary regulator of companies that have too often misbehaved.
Here we discussed her position on the board of directors of Henry Schein, Inc a medical supply company. My concern was whether someone who had spent years being ultimately responsible for maximizing the profits of a medical supply company would be able to be a fair, and when necessary, tough regulator of the companies that supply Henry Schein with products to sell.
Here we discussed Dr Hamburg's husband's leadership of the hedge fund management company, Renaissance Technologies. My concern was whether someone who is part of a family that had gotten rich from buying and selling stocks and financial instruments, of which a likely substantial but unknown fraction were of health care corporations, would again be able to be a fair, and when necessary tough regulator of some of these same companies.
At the time, it did not seem that anyone else shared these concerns. As far as I could tell, there was no discussion of them in the press, or at Dr Hamburg's confirmation hearings.
However, today the Wall Street Journal reported:
The new commissioner of the Food and Drug Administration is among the wealthiest Obama administration appointees, with income of at least $10 million in 2008 thanks mostly to her husband, a hedge-fund executive, according to financial disclosure forms.
Margaret Hamburg and her husband, Peter Fitzhugh Brown, must divest themselves of several hedge-fund holdings as well as some of Mr. Brown's inherited drug-company stocks so Dr. Hamburg can take the post as the nation's top food and drug regulator. Mr. Brown is a lieutenant to hedge-fund magnate James Simons
The couple's income in 2008 came from stocks, money-market accounts, trusts and funds including several affiliated with hedge-fund sponsor Renaissance Technologies, where Mr. Brown works.
The couple controls assets worth between $21 million and $40 million, according to disclosure forms Dr. Hamburg gave the White House. The forms don't reveal exact figures, just ranges.
Before her FDA nomination, Dr. Hamburg also served for five years on the board of Henry Schein Inc., a $4 billion firm that distributes medical and dental supplies including vaccines. Her remuneration has been in the form of Schein shares.
She will forfeit $100,000 to $250,000 in restricted stock and more than 11,000 unvested stock options, all of which have a strike price above market value. She will also have to sell vested stock, valued between $250,000 and $500,000.
Mr. Brown, an expert in artificial intelligence, is vice president and director at Renaissance Technologies. The fund company said recently its total assets were about $18 billion. Mr. Simons was the top-paid hedge-fund manager in 2008, receiving $2.5 billion, according to Alpha magazine.
A lengthy review by the Government Ethics Office, which included direct discussions with Renaissance managers, determined that both Dr. Hamburg and her husband will have to get rid of their interest in four Renaissance funds—the Renaissance Institutional Equities Fund, the Renaissance Institutional Futures Fund, Meritage Investors and Topspin Partners.
However, the couple will be allowed to retain their interest in Renaissance's Medallion fund. An administration official said Medallion was exempted because its computerized quantitative model trades rapidly and holds shares only briefly, creating the equivalent of 'a very blind trust.'
Mr. Brown has already sold his stock in Abbott Laboratories and shares in Johnson & Johnson, Merck & Co. and Medco Health Solutions Inc., which he inherited from his father.
So it appears, in retrospect, that the Government Ethics Office also felt that Dr Hamburg's position on the Henry Schein Inc board constituted a conflict of interest. Furthermore, the Office felt that Dr Hamburg's and Mr Brown's holdings in several hedge funds constituted conflicts of interest. So, in retrospect, it is odd that these financial relationships attracted no attention other than that of Health Care Renewal prior to Dr Hamburg's confirmation by the Senate. I do hope that now, having severed significant relationships and sold financial holdings, Dr Hamburg will prove to be a fair, and tough when necessary regulator of companies that have too often misbehaved.
What Influenced a Paean to Karen Ignagne?
As the discussion here in the US about health care reform gathers steam, the Washington Post published a rather uncritical profile of one of the prominent participants, Ms Karen Ignagni, CEO of America's Health Insurance Plans (AHIP), the trade group for the health insurance/ managed care industry. It included some compliments from Princeton Professor and prominent health care economist Uwe Reinhardt:
What the Washington Post article did not bother to mention was that in addition to being on the Princeton faculty, Professor Reinhardt is a member of the board of directors of Amerigroup, a health insurance company specializing in providing Medicaid and Medicare managed care (see this previous post), and a member of AHIP. Former Amerigroup CEO Jeffrey McWalters was on the board of AHIP. According to Amerigroup's 2009 proxy statement, Professor Reinhardt controls (via ownership or options) 144,558 shares of Amerigroup stock, and received $226,531 in compensation from Amerigroup in 2008.
Perhaps Professor Reinhardt's enthusiasm for Karen Ignagne's performance as CEO of AHIP derived more from his leadership of Amerigroup than a scholarly analysis.
Note also that Professor Reinhardt is a member of the board of directors of Boston Scientific, a medical device company. Furthermore, per proxy statements from the above companies, Professor Reinhardt is on the board of two funds from H&Q Healthcare Investors, and is a Trustee of Duke University and the Duke University Health System.
Professor Reinhardt's leadership roles in US publicly traded corporations are public, but not easily found unless one knows where to look. We had first discussed these relationships on Health Care Renewal in 2006. However, many of the more academically tinged biographies of him publicly available omit his leadership roles in the for-profit world. At the moment, biographies of Professor Reinhardt on the Princeton web-site, and furnished by the Princeton Bioethics Forum, the Commonwealth Fund, and the Henry J Kaiser Foundation did not note these relationships.
This illustrates once more participation in the current health policy debate may be driven by vested interests, rather than ideology, much less dispassionate analysis. Were the participants yo disclose, at least, their financial interests, the debate would become that much clearer. Meanwhile, when listening to the debate, always ask, "cui bono?" (Who benefits?)
Hat tip to the Health Care Blog.
'Whatever AHIP pays her, it's not enough. She's unbelievably effective,' said Princeton economist Uwe Reinhardt. 'It's just amazing what she's achieved for them against all odds.'
Ignagni's total compensation, according to AHIP's most recent filing from 2007, was $1.58 million, which includes $700,000 in base salary, $370,000 in deferred compensation and a bonus. Ignagni won't say how many hours a week she works. The number's so high it's embarrassing, she said.
Among successes cited by Reinhardt and others is helping persuade the Bush administration to develop private insurance plans within Medicare that are producing unexpectedly high payments for private insurers.
What the Washington Post article did not bother to mention was that in addition to being on the Princeton faculty, Professor Reinhardt is a member of the board of directors of Amerigroup, a health insurance company specializing in providing Medicaid and Medicare managed care (see this previous post), and a member of AHIP. Former Amerigroup CEO Jeffrey McWalters was on the board of AHIP. According to Amerigroup's 2009 proxy statement, Professor Reinhardt controls (via ownership or options) 144,558 shares of Amerigroup stock, and received $226,531 in compensation from Amerigroup in 2008.
Perhaps Professor Reinhardt's enthusiasm for Karen Ignagne's performance as CEO of AHIP derived more from his leadership of Amerigroup than a scholarly analysis.
Note also that Professor Reinhardt is a member of the board of directors of Boston Scientific, a medical device company. Furthermore, per proxy statements from the above companies, Professor Reinhardt is on the board of two funds from H&Q Healthcare Investors, and is a Trustee of Duke University and the Duke University Health System.
Professor Reinhardt's leadership roles in US publicly traded corporations are public, but not easily found unless one knows where to look. We had first discussed these relationships on Health Care Renewal in 2006. However, many of the more academically tinged biographies of him publicly available omit his leadership roles in the for-profit world. At the moment, biographies of Professor Reinhardt on the Princeton web-site, and furnished by the Princeton Bioethics Forum, the Commonwealth Fund, and the Henry J Kaiser Foundation did not note these relationships.
This illustrates once more participation in the current health policy debate may be driven by vested interests, rather than ideology, much less dispassionate analysis. Were the participants yo disclose, at least, their financial interests, the debate would become that much clearer. Meanwhile, when listening to the debate, always ask, "cui bono?" (Who benefits?)
Hat tip to the Health Care Blog.
Eicosanoids and Ischemic Heart Disease
Dr. William Lands, one of the pioneers of the eicosanoid field, compiled this graph. It may be the single most important clue we have about the relationship between diet and ischemic heart disease (heart attacks).To explain it fully, we have to take a few steps back. Dietary polyunsaturated fatty acids (PUFA) are primarily omega-6 and omega-3. This is a chemical designation that refers to the position of a double bond along the fatty acid's carbon chain. Omega-6 fats are found abundantly in industrial vegetable oils (corn, soybean, sunflower, cottonseed, etc.) and certain nuts, and in lesser amounts in meats, dairy and grains. Omega-3 fats are found abundantly in seafood and a few seeds such as flax and walnuts, and in smaller amounts in meats, green vegetables and dairy.
The body uses a multi-step process to convert omega-3 and omega-6 fats into eicosanoids, which are a diverse and potent class of signaling molecules. The first step is to convert PUFA into highly unsaturated fatty acids, or HUFA. These include arachidonic acid (AA), an omega-6 HUFA, eicosapentaenoic acid (EPA), an omega-3 HUFA, and several others in the 20- to 22-carbon length range.
HUFA are stored in cell membranes and they are the direct precursors of eicosanoids. When the cell needs eicosanoids, it liberates HUFA from the membrane and converts it. The proportion of omega-6 to omega-3 HUFA in the membrane is proportional to the long-term proportion of omega-6 and omega-3 in the diet. Enzymes do not discriminate between omega-6 and omega-3 HUFA when they create eicosanoids. Therefore, the proportion of omega-6- to omega-3-derived eicosanoids is proportional to dietary intake.
Omega-6 eicosanoids are potently inflammatory and thrombotic (promote blood clotting, such as thromboxane A2), while omega-3 eicosanoids are less inflammatory, less thrombotic and participate in long-term repair processes.
Many of the studies that have looked at the relationship between HUFA and heart attacks used blood plasma (serum lipids). Dr. Lands has pointed out that plasma HUFA do not accurately reflect dietary omega-6/3 balance, and they don't correlate well with heart attack risk. What does correlate strikingly well with both dietary intake and heart attack risk is the proportion of omega-6 HUFA in tissue, which reflects the amount contained in cell membranes. That's what we're looking at in the graph above: the proportion of omega-6 HUFA in the total tissue HUFA pool, vs. coronary heart disease death rate.
You can see that the correlation is striking, both between populations and within them. Greenland Inuit have the lowest proportion of omega-6 HUFA, due to a low intake of omega-6 and an exceptionally high intake of seafood. They also have an extraordinarily low risk of heart attack death. The red dots are from the Multiple Risk Factor Intervention Trial (MRFIT), which I'll be covering in a bit more detail in a later post. They're important because they confirm that the trend holds true within a population, and not just between populations.
In the next post, I'll be delving into this concept in more detail, and explaining why it's not just the ratio that matters, but also the total intake of omega-6. I'll also be providing more evidence to support the theory.
Eicosanoids and Ischemic Heart Disease
Dr. William Lands, one of the pioneers of the eicosanoid field, compiled this graph. It may be the single most important clue we have about the relationship between diet and ischemic heart disease (heart attacks).To explain it fully, we have to take a few steps back. Dietary polyunsaturated fatty acids (PUFA) are primarily omega-6 and omega-3. This is a chemical designation that refers to the position of a double bond along the fatty acid's carbon chain. Omega-6 fats are found abundantly in industrial vegetable oils (corn, soybean, sunflower, cottonseed, etc.) and certain nuts, and in lesser amounts in meats, dairy and grains. Omega-3 fats are found abundantly in seafood and a few seeds such as flax and walnuts, and in smaller amounts in meats, green vegetables and dairy.
The body uses a multi-step process to convert omega-3 and omega-6 fats into eicosanoids, which are a diverse and potent class of signaling molecules. The first step is to convert PUFA into highly unsaturated fatty acids, or HUFA. These include arachidonic acid (AA), an omega-6 HUFA, eicosapentaenoic acid (EPA), an omega-3 HUFA, and several others in the 20- to 22-carbon length range.
HUFA are stored in cell membranes and they are the direct precursors of eicosanoids. When the cell needs eicosanoids, it liberates HUFA from the membrane and converts it. The proportion of omega-6 to omega-3 HUFA in the membrane is proportional to the long-term proportion of omega-6 and omega-3 in the diet. Enzymes do not discriminate between omega-6 and omega-3 HUFA when they create eicosanoids. Therefore, the proportion of omega-6- to omega-3-derived eicosanoids is proportional to dietary intake.
Omega-6 eicosanoids are potently inflammatory and thrombotic (promote blood clotting, such as thromboxane A2), while omega-3 eicosanoids are less inflammatory, less thrombotic and participate in long-term repair processes.
Many of the studies that have looked at the relationship between HUFA and heart attacks used blood plasma (serum lipids). Dr. Lands has pointed out that plasma HUFA do not accurately reflect dietary omega-6/3 balance, and they don't correlate well with heart attack risk. What does correlate strikingly well with both dietary intake and heart attack risk is the proportion of omega-6 HUFA in tissue, which reflects the amount contained in cell membranes. That's what we're looking at in the graph above: the proportion of omega-6 HUFA in the total tissue HUFA pool, vs. coronary heart disease death rate.
You can see that the correlation is striking, both between populations and within them. Greenland Inuit have the lowest proportion of omega-6 HUFA, due to a low intake of omega-6 and an exceptionally high intake of seafood. They also have an extraordinarily low risk of heart attack death. The red dots are from the Multiple Risk Factor Intervention Trial (MRFIT), which I'll be covering in a bit more detail in a later post. They're important because they confirm that the trend holds true within a population, and not just between populations.
In the next post, I'll be delving into this concept in more detail, and explaining why it's not just the ratio that matters, but also the total intake of omega-6. I'll also be providing more evidence to support the theory.
BLOGSCAN - Comparative Effectiveness Research, the Partnership to Improve Patient Care, and PhRMA
On the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody dissected a campaign to redirect comparative effectiveness research by making it responsible to a new governing board that would include "insurance" and "industry" members. And surprise, surprise, the campaign is run by the Partnership to Improve Patient Care, a group that seems to have multiple connections to PhRMA, the pharmaceutical industry trade organization. More stealth health policy advocacy?
Eicosanoids, Fatty Liver and Insulin Resistance
I have to take a brief intermission from the heart disease series to write about a very important paper I just read in the journal Obesity, "COX-2-mediated Inflammation in Fat is Crucial for Obesity-linked Insulin Resistance and Fatty Liver". It's actually related to cardiovascular disease, although indirectly.
First, some background. Polyunsaturated fatty acids (PUFA) come mostly from omega-6 and omega-3 sources. Omega-6 and omega-3 are precursors to eicosanoids, a large and poorly understood class of signaling molecules that play a role in basically everything. Eicosanoids are either omega-6-derived or omega-3-derived. Omega-6 and omega-3 compete for the enzymes that convert PUFA into eicosanoids. Therefore, the ratio of omega-6 to omega-3 in tissues (related to the ratio in the diet) determines the ratio of omega-6-derived eicosanoids to omega-3-derived eicosanoids.
Omega-6 eicosanoids are very potent and play a central role in inflammation. They aren't "bad", in fact they're essential, but an excess of them is probably not good. Omega-3 eicosanoids are generally less potent, less inflammatory, and tend to participate in long-term repair processes. So in sum, the ratio of omega-6 to omega-3 in the diet will determine the potency and quality of eicosanoid signaling, which will determine an animal's susceptibility to inflammation-mediated disorders.
One of the key enzymes in the pathway from PUFA to eicosanoids (specifically, a subset of them called prostanoids) is cyclooxygenase (COX). COX-1 is expressed all the time and serves a "housekeeping" function, while COX-2 is induced by cellular stressors and contributes to the the formation of inflammatory eicosanoids. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit COX enzymes, which is why they are effective against inflammatory problems like pain and fever. They are also used as a preventive measure against cardiovascular disease. Basically, they reduce the excessive inflammatory signaling promoted by a diet with a poor omega-6:3 balance. You wouldn't need to inhibit COX if it were producing the proper balance of eicosanoids to begin with.
Dr. Kuang-Chung Shih's group at the Department of Internal Medicine in Taipei placed rats on five different diets:
Rats in group 2 not only gained weight, they also experienced increased fasting glucose, leptin, insulin, triglycerides, blood pressure and a massive decline in insulin sensitivity (seven-fold relative to group 1). Rats in groups 3 and 4 gained weight, but saw much less of a deterioration in insulin and leptin sensitivity, and blood pressure. Group 2 also developed fatty liver, which was attenuated in groups 3 and 4. If you're interested, group 5 (energy restricted high-fat) was similar to groups 3 and 4 on pretty much everything, including insulin sensitivity.
So there you have it folks: direct evidence that insulin resistance, leptin resistance, high blood pressure and fatty liver are mediated by excessive inflammatory eicosanoid signaling. I wrote about something similar before when I reviewed a paper showing that fish oil reverses many of the consequences of a high-vegetable oil, high-sugar diet in rats. I also reviewed two papers showing that in pigs and rats, a high omega-6:3 ratio promotes inflammation (mediated by COX-2) and lipid peroxidation in the heart. Are you going to quench the fire by taking drugs, or by reducing your intake of omega-6 and ensuring an adequate intake of omega-3?
*Of course, they didn't mention the sucrose in the methods section. I had to go digging around for the diet's composition. This is typical of papers on "high-fat diets". They load them up with sugar, and blame everything on the fat.
**Rats gain fat mass when fed a high-fat diet (even if it's not loaded with sugar). But humans don't necessarily gain weight on a high-fat diet (i.e. low-carb weight loss diet). What's the difference? Low-carbohydrate diet trials indicate that humans spontaneously reduce their caloric intake when eating low carbohydrate, high-fat food.
First, some background. Polyunsaturated fatty acids (PUFA) come mostly from omega-6 and omega-3 sources. Omega-6 and omega-3 are precursors to eicosanoids, a large and poorly understood class of signaling molecules that play a role in basically everything. Eicosanoids are either omega-6-derived or omega-3-derived. Omega-6 and omega-3 compete for the enzymes that convert PUFA into eicosanoids. Therefore, the ratio of omega-6 to omega-3 in tissues (related to the ratio in the diet) determines the ratio of omega-6-derived eicosanoids to omega-3-derived eicosanoids.
Omega-6 eicosanoids are very potent and play a central role in inflammation. They aren't "bad", in fact they're essential, but an excess of them is probably not good. Omega-3 eicosanoids are generally less potent, less inflammatory, and tend to participate in long-term repair processes. So in sum, the ratio of omega-6 to omega-3 in the diet will determine the potency and quality of eicosanoid signaling, which will determine an animal's susceptibility to inflammation-mediated disorders.
One of the key enzymes in the pathway from PUFA to eicosanoids (specifically, a subset of them called prostanoids) is cyclooxygenase (COX). COX-1 is expressed all the time and serves a "housekeeping" function, while COX-2 is induced by cellular stressors and contributes to the the formation of inflammatory eicosanoids. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit COX enzymes, which is why they are effective against inflammatory problems like pain and fever. They are also used as a preventive measure against cardiovascular disease. Basically, they reduce the excessive inflammatory signaling promoted by a diet with a poor omega-6:3 balance. You wouldn't need to inhibit COX if it were producing the proper balance of eicosanoids to begin with.
Dr. Kuang-Chung Shih's group at the Department of Internal Medicine in Taipei placed rats on five different diets:
- A control diet, eating normal low-fat rat chow.
- A "high-fat diet", in which 45% of calories came from a combination of industrial lard and soybean oil, and 17% of calories came from sucrose*.
- A "high-fat diet" (same as above), plus the COX-2 inhibitor celecoxib (Celebrex).
- A "high-fat diet" (same as above), plus the COX-2 inhibitor mesulid.
- An energy-restricted "high-fat diet".
Rats in group 2 not only gained weight, they also experienced increased fasting glucose, leptin, insulin, triglycerides, blood pressure and a massive decline in insulin sensitivity (seven-fold relative to group 1). Rats in groups 3 and 4 gained weight, but saw much less of a deterioration in insulin and leptin sensitivity, and blood pressure. Group 2 also developed fatty liver, which was attenuated in groups 3 and 4. If you're interested, group 5 (energy restricted high-fat) was similar to groups 3 and 4 on pretty much everything, including insulin sensitivity.
So there you have it folks: direct evidence that insulin resistance, leptin resistance, high blood pressure and fatty liver are mediated by excessive inflammatory eicosanoid signaling. I wrote about something similar before when I reviewed a paper showing that fish oil reverses many of the consequences of a high-vegetable oil, high-sugar diet in rats. I also reviewed two papers showing that in pigs and rats, a high omega-6:3 ratio promotes inflammation (mediated by COX-2) and lipid peroxidation in the heart. Are you going to quench the fire by taking drugs, or by reducing your intake of omega-6 and ensuring an adequate intake of omega-3?
*Of course, they didn't mention the sucrose in the methods section. I had to go digging around for the diet's composition. This is typical of papers on "high-fat diets". They load them up with sugar, and blame everything on the fat.
**Rats gain fat mass when fed a high-fat diet (even if it's not loaded with sugar). But humans don't necessarily gain weight on a high-fat diet (i.e. low-carb weight loss diet). What's the difference? Low-carbohydrate diet trials indicate that humans spontaneously reduce their caloric intake when eating low carbohydrate, high-fat food.
Eicosanoids, Fatty Liver and Insulin Resistance
I have to take a brief intermission from the heart disease series to write about a very important paper I just read in the journal Obesity, "COX-2-mediated Inflammation in Fat is Crucial for Obesity-linked Insulin Resistance and Fatty Liver". It's actually related to cardiovascular disease, although indirectly.
First, some background. Polyunsaturated fatty acids (PUFA) come mostly from omega-6 and omega-3 sources. Omega-6 and omega-3 are precursors to eicosanoids, a large and poorly understood class of signaling molecules that play a role in basically everything. Eicosanoids are either omega-6-derived or omega-3-derived. Omega-6 and omega-3 compete for the enzymes that convert PUFA into eicosanoids. Therefore, the ratio of omega-6 to omega-3 in tissues (related to the ratio in the diet) determines the ratio of omega-6-derived eicosanoids to omega-3-derived eicosanoids.
Omega-6 eicosanoids are very potent and play a central role in inflammation. They aren't "bad", in fact they're essential, but an excess of them is probably not good. Omega-3 eicosanoids are generally less potent, less inflammatory, and tend to participate in long-term repair processes. So in sum, the ratio of omega-6 to omega-3 in the diet will determine the potency and quality of eicosanoid signaling, which will determine an animal's susceptibility to inflammation-mediated disorders.
One of the key enzymes in the pathway from PUFA to eicosanoids (specifically, a subset of them called prostanoids) is cyclooxygenase (COX). COX-1 is expressed all the time and serves a "housekeeping" function, while COX-2 is induced by cellular stressors and contributes to the the formation of inflammatory eicosanoids. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit COX enzymes, which is why they are effective against inflammatory problems like pain and fever. They are also used as a preventive measure against cardiovascular disease. Basically, they reduce the excessive inflammatory signaling promoted by a diet with a poor omega-6:3 balance. You wouldn't need to inhibit COX if it were producing the proper balance of eicosanoids to begin with.
Dr. Kuang-Chung Shih's group at the Department of Internal Medicine in Taipei placed rats on five different diets:
Rats in group 2 not only gained weight, they also experienced increased fasting glucose, leptin, insulin, triglycerides, blood pressure and a massive decline in insulin sensitivity (seven-fold relative to group 1). Rats in groups 3 and 4 gained weight, but saw much less of a deterioration in insulin and leptin sensitivity, and blood pressure. Group 2 also developed fatty liver, which was attenuated in groups 3 and 4. If you're interested, group 5 (energy restricted high-fat) was similar to groups 3 and 4 on pretty much everything, including insulin sensitivity.
So there you have it folks: direct evidence that insulin resistance, leptin resistance, high blood pressure and fatty liver are mediated by excessive inflammatory eicosanoid signaling. I wrote about something similar before when I reviewed a paper showing that fish oil reverses many of the consequences of a high-vegetable oil, high-sugar diet in rats. I also reviewed two papers showing that in pigs and rats, a high omega-6:3 ratio promotes inflammation (mediated by COX-2) and lipid peroxidation in the heart. Are you going to quench the fire by taking drugs, or by reducing your intake of omega-6 and ensuring an adequate intake of omega-3?
*Of course, they didn't mention the sucrose in the methods section. I had to go digging around for the diet's composition. This is typical of papers on "high-fat diets". They load them up with sugar, and blame everything on the fat.
**Rats gain fat mass when fed a high-fat diet (even if it's not loaded with sugar). But humans don't necessarily gain weight on a high-fat diet (i.e. low-carb weight loss diet). What's the difference? Low-carbohydrate diet trials indicate that humans spontaneously reduce their caloric intake when eating low carbohydrate, high-fat food.
First, some background. Polyunsaturated fatty acids (PUFA) come mostly from omega-6 and omega-3 sources. Omega-6 and omega-3 are precursors to eicosanoids, a large and poorly understood class of signaling molecules that play a role in basically everything. Eicosanoids are either omega-6-derived or omega-3-derived. Omega-6 and omega-3 compete for the enzymes that convert PUFA into eicosanoids. Therefore, the ratio of omega-6 to omega-3 in tissues (related to the ratio in the diet) determines the ratio of omega-6-derived eicosanoids to omega-3-derived eicosanoids.
Omega-6 eicosanoids are very potent and play a central role in inflammation. They aren't "bad", in fact they're essential, but an excess of them is probably not good. Omega-3 eicosanoids are generally less potent, less inflammatory, and tend to participate in long-term repair processes. So in sum, the ratio of omega-6 to omega-3 in the diet will determine the potency and quality of eicosanoid signaling, which will determine an animal's susceptibility to inflammation-mediated disorders.
One of the key enzymes in the pathway from PUFA to eicosanoids (specifically, a subset of them called prostanoids) is cyclooxygenase (COX). COX-1 is expressed all the time and serves a "housekeeping" function, while COX-2 is induced by cellular stressors and contributes to the the formation of inflammatory eicosanoids. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit COX enzymes, which is why they are effective against inflammatory problems like pain and fever. They are also used as a preventive measure against cardiovascular disease. Basically, they reduce the excessive inflammatory signaling promoted by a diet with a poor omega-6:3 balance. You wouldn't need to inhibit COX if it were producing the proper balance of eicosanoids to begin with.
Dr. Kuang-Chung Shih's group at the Department of Internal Medicine in Taipei placed rats on five different diets:
- A control diet, eating normal low-fat rat chow.
- A "high-fat diet", in which 45% of calories came from a combination of industrial lard and soybean oil, and 17% of calories came from sucrose*.
- A "high-fat diet" (same as above), plus the COX-2 inhibitor celecoxib (Celebrex).
- A "high-fat diet" (same as above), plus the COX-2 inhibitor mesulid.
- An energy-restricted "high-fat diet".
Rats in group 2 not only gained weight, they also experienced increased fasting glucose, leptin, insulin, triglycerides, blood pressure and a massive decline in insulin sensitivity (seven-fold relative to group 1). Rats in groups 3 and 4 gained weight, but saw much less of a deterioration in insulin and leptin sensitivity, and blood pressure. Group 2 also developed fatty liver, which was attenuated in groups 3 and 4. If you're interested, group 5 (energy restricted high-fat) was similar to groups 3 and 4 on pretty much everything, including insulin sensitivity.
So there you have it folks: direct evidence that insulin resistance, leptin resistance, high blood pressure and fatty liver are mediated by excessive inflammatory eicosanoid signaling. I wrote about something similar before when I reviewed a paper showing that fish oil reverses many of the consequences of a high-vegetable oil, high-sugar diet in rats. I also reviewed two papers showing that in pigs and rats, a high omega-6:3 ratio promotes inflammation (mediated by COX-2) and lipid peroxidation in the heart. Are you going to quench the fire by taking drugs, or by reducing your intake of omega-6 and ensuring an adequate intake of omega-3?
*Of course, they didn't mention the sucrose in the methods section. I had to go digging around for the diet's composition. This is typical of papers on "high-fat diets". They load them up with sugar, and blame everything on the fat.
**Rats gain fat mass when fed a high-fat diet (even if it's not loaded with sugar). But humans don't necessarily gain weight on a high-fat diet (i.e. low-carb weight loss diet). What's the difference? Low-carbohydrate diet trials indicate that humans spontaneously reduce their caloric intake when eating low carbohydrate, high-fat food.
"A Breach of Trust"
This new variation on a now old theme first appeared in the New York Times:
This story has several familiar elements, but combines them in some interesting ways.
We have discussed how health care corporations, particularly pharmaceutical manufacturers, cultivate "key opinion leaders," and use them to market their products. This may amount to stealth marketing, since KOLs rarely disclose in detail their relationships with corporate sponsors, and instead further their marketing objectives cloaked as academics.
We have also discussed how health care corporations, particularly pharmaceutical manufacturers, may sponsor clinical research on their own products. However, such sponsors often manipulate the research projects' design, implementation, analysis, and dissemination so as to favor their products. While the sponsorship may be disclosed, the extent of the sponsors' control over the project may not be. Furthermore, scientific investigators running such projects may have their own personal financial relationships with the sponsors.
This case apparently shows how a medical academic can both be a paid "key opinion leader," and manipulative clinical researcher. While many examples of key opinion leaders as stealth marketers, and manipulated research involved pharmaceutical companies, this one involves a medical device company. In addition, this research project was not just manipulated, but allegedly falsified.
This variation has at least one other interesting element. Again, from the New York Times,
Furthermore, the New York Times reported,
The most recent development, again according to the NY Times, is
Finally, note that we posted last year that Medtronic had submitted to a corporate integrity agreement after the US Department of Justice accused it of defrauding Medicare in connection with activities by its Kyphon subsidiary. So this case additionally suggests that such agreements have little effect on the actual integrity of corporate leaders.
Hat tip to and see further commentary by Prof Margaret Soltan on the University Diaries blog.
ADDENDUM (24 May, 2009) - see further comments by Prof Soltan on the University Diaries blog.
A former surgeon at Walter Reed Army Medical Center, who is a paid consultant for a medical company, published a study that made false claims and overstated the benefits of the company’s product in treating soldiers severely injured in Iraq, the hospital’s commander said Tuesday.An investigation by Walter Reed found that the study cited higher numbers of patients and injuries than the hospital could account for, said the commander, Col. Norvell V. Coots.
'It’s like a ghost population that were reported in the article as having been treated that we have no record of ever having existed,' Colonel Coots said in a telephone interview on Tuesday. 'So this really was all falsified information.'
The former Army surgeon, Dr. Timothy R. Kuklo, reported that a bone-growth product sold by Medtronic Inc. had much higher success in healing the shattered legs of wounded soldiers at Walter Reed than other doctors there had experienced, according to Colonel Coots and a summary of an Army investigation of the matter.
Dr. Kuklo, 48, now an associate professor at the Washington University medical school in St. Louis, did not respond to numerous e-mail messages and telephone calls to his office and home seeking comment over the last two weeks. Walter Reed officials say he did not respond to their inquiries during their investigation.
Army investigators found that Dr. Kuklo forged the signatures of four Walter Reed doctors on the article before submitting it last year to a British medical journal, falsely claiming them as co-authors. He also did not obtain the Army’s required permission to conduct the study.
In its March edition, at the Army’s request, the journal retracted the article — something that has gone largely unnoticed outside orthopedic circles.
While at Walter Reed and since, Dr. Kuklo has given talks to other doctors around the country about the bone-growth product, a protein called Infuse, according to meeting agendas and published documents.
A Medtronic spokeswoman, Marybeth Thorsgaard, confirmed that Dr. Kuklo was a paid consultant to the company and that the company financially supported some of his research at Walter Reed, through a foundation affiliated with the hospital.
During his time at Walter Reed Dr. Kuklo was extensively involved in research and writing about various Medtronic products, including editing two books published by the company and conducting three studies that were approved by his Army superiors, according to his list of publications and an Army report.
Colonel Coots said Tuesday that the total number of patients Dr. Kuklo reported as having been treated for extensive lower leg wounds at Walter Reed during the study period — 138 soldiers — was greater than the number for which the hospital could find records.
'It is a significant breach of academic protocol,' Colonel Coots said. 'It’s a breach of trust.'
This story has several familiar elements, but combines them in some interesting ways.
We have discussed how health care corporations, particularly pharmaceutical manufacturers, cultivate "key opinion leaders," and use them to market their products. This may amount to stealth marketing, since KOLs rarely disclose in detail their relationships with corporate sponsors, and instead further their marketing objectives cloaked as academics.
We have also discussed how health care corporations, particularly pharmaceutical manufacturers, may sponsor clinical research on their own products. However, such sponsors often manipulate the research projects' design, implementation, analysis, and dissemination so as to favor their products. While the sponsorship may be disclosed, the extent of the sponsors' control over the project may not be. Furthermore, scientific investigators running such projects may have their own personal financial relationships with the sponsors.
This case apparently shows how a medical academic can both be a paid "key opinion leader," and manipulative clinical researcher. While many examples of key opinion leaders as stealth marketers, and manipulated research involved pharmaceutical companies, this one involves a medical device company. In addition, this research project was not just manipulated, but allegedly falsified.
This variation has at least one other interesting element. Again, from the New York Times,
A former Walter Reed colleague, Dr. David W. Polly Jr., who is also a Medtronic consultant, said he believed that Dr. Kuklo’s data was “strong” and the episode had been overblown.According to the Center for Public Integrity Paper Trail blog,
A former colleague of Kuklo’s at Walter Reed Army Medical Center, Dr. David W. Polly Jr., took even more expensive trips than Kuklo. Polly went on at least 12 Medtronic-sponsored trips costing about $30,000, including a $10,000 trip to Switzerland.
Furthermore, the New York Times reported,
[Senator Charles] Grassley, the ranking Republican [from Iowa] on the Senate Finance Committee, has been investigating since last year whether Medtronic illegally promoted unapproved uses for Infuse. Medtronic, which has denied that accusation, provided him last year with a list of Infuse consultants.So, as soon as this case came to light, the spinning of public discussion to favor Medtronic and its key opinion leaders began. Thus, this case also involved stealth policy advocacy. Stealth marketing, clinical research manipulation, and stealth advocacy all in one case, we seem to have hit the jackpot.
After Dr. Kuklo’s links to Medtronic and Infuse came to light last week in a New York Times article, Mr. Grassley’s staff checked the consultants list and noted that Dr. Kuklo’s name was not on it. In reaction, he wrote a letter to Medtronic’s president and chief executive, William A. Hawkins III, asking why Dr. Kuklo had been omitted. Mr. Grassley entered that letter and the list he had received into The Congressional Record.
'In the future, I hope that instead of not providing me with the name of the physician involved in Infuse, or any other matter that I am looking into, that Medtronic contact me to avoid the situation in which we find ourselves,' Mr. Grassley wrote to Mr. Hawkins.
The most recent development, again according to the NY Times, is
At least his absence was not ascribed to the need to spend more time with his family or pursue other opportunities.
Dr. Timothy R. Kuklo, a former Army physician accused of falsifying research involving injured soldiers, has taken a leave of absence from the Washington University School of Medicine in St. Louis and its affiliated hospitals, the medical school said Friday.
Dr. Kuklo, an associate professor of orthopedic surgery, will not be performing operations, conducting research or teaching students, said a medical school spokeswoman, Joni Westerhouse. The university granted the leave, she said, so that Dr. Kuklo 'can focus on responding to queries about his research and consulting.'
Finally, note that we posted last year that Medtronic had submitted to a corporate integrity agreement after the US Department of Justice accused it of defrauding Medicare in connection with activities by its Kyphon subsidiary. So this case additionally suggests that such agreements have little effect on the actual integrity of corporate leaders.
Hat tip to and see further commentary by Prof Margaret Soltan on the University Diaries blog.
ADDENDUM (24 May, 2009) - see further comments by Prof Soltan on the University Diaries blog.
BLOGSCAN - "Money-Driven Medicine," the Film
On the Health Care Blog, Maggie Mahar announced the screening of the new documentary film based on her book "Money-Driven Medicine."
HealthSouth's "Digital Hospital," from the "Era of Cyber Hospitals" to an Unfinished "Pipe Dream"
The trial for a civil law-suit against Richard Scrushy, the former CEO of for-profit rehabilitation hospital chain HealthSouth, is currently in progress. One bit of testimony provided a reminder about how supposed "innovations" in health care are uncritically accepted. As reported by the Birmingham (Alabama, US) News:
In additional coverage by a local television station (NBC13.com),
What a contrast this was to the hype that surrounded the announcement of Scrushy's intention to build the "digital hospital." Let me provide some samples.
ComputerWorld allowed Scrushy to wax eloquent:
Bio-Medicine gushed:
Managed Care Magazine was only somewhat more measured:
An article in the MIT Technology Review was just a little bit skeptical:
But the article's conclusion was less cautious:
Finally, I was able to find some discussion of the proposed "digital hospital" in a scholarly publication, in fact, in probably the most authoritative and well-read journal on health care policy in the US, Health Affairs. [Burns LR, Pauly MV. Integrated delivery networks: a detour on the road to integrated health care? Health Affairs 2002; 21: 128-143.] I would not call it gushy, but it hardly seemed skeptical:
So we have gone from "the hospital model for the world," with great "promise," which "could save lives," proclaiming the "era of cyber hospitals," to a "pipe dream," just the shell of half-finished building.
So I wonder, if one were to identify every highly hyped, rapidly spun, magic new "innovation" promising to revolutionize patient care, and follow them forward in time, how many would even marginally improve health care, or provide benefits that marginally out-weighed their harms? How many would never come to be, or prove to be unworkable, useless, or even harmful?
But the short-term incentives for leaders of health care organizations push them to announce innovation after innovation, collect their bonuses and perks, and be somewhere else by the time their wondrous innovations prove to be not so good.
Keep in mind that some heavily promoted innovations, such as new pharmaceuticals, must be subject to randomized controlled trials and government approval. Yet, as perusing Health Care Renewal will show, many pharmaceutical companies have managed to make their glitzy innovations appear more efficacious and less hazardous by lavish, shrewd, and sometimes deceptive marketing, and by manipulating clinical research, and sometimes suppressing results. Medical devices are not subject to as much scrutiny. Health care information technology, and programmatic innovations by hospitals, health systems, managed care and health insurance companies can appear without any research evidence to support them.
This is why we all should be extremely skeptical of whatever new "innovations" our multi-million dollar health care CEOs and their cronies are hawking these days.
HealthSouth Corp. Chief Executive Jay Grinney has concluded his testimony in the Richard Scrushy civil trial, ending with a devastating critique of the so-called 'digital hospital.'
'It was a very bad business decision that made no sense,' Grinney said of the half-completed Scrushy brainchild on U.S. 280 he inherited when he took over in 2004.
Ending his sixth hour of testimony over two days, Grinney said the hospital had an original budget of $200 million, and that much had already been spent when the the project was stopped halfway through. Another $200 million was required, he said.
When it came time to cut the $3.5 billion of debt that was burdening the company, Grinney said he had no hesitation about selling the building. Scrushy had envisioned the medical center as a 200-bed centerpiece of the HealthSouth empire, and called it the 'digital hospital' because of its planned technology component.
The building has been sold to real-estate developers,....
Scrushy is on trial in Jefferson County Circuit Court after being sued by HealthSouth shareholders. They are seeking $2.6 billion in damages from him for costs related to accounting fraud, corporate waste and insider stock trading while he ran the physical therapy company from 1996 through 2002
The 56-year-old Selma native is in the Shelby County Jail awaiting his court appearance in the case. He was brought to Birmingham from federal prison in Texas, where he is two years into a seven-year sentence for bribing former Alabama Gov. Don Siegelman.
In additional coverage by a local television station (NBC13.com),
When asked about the unfinished digital hospital on Highway 280, Grinney said, 'It was a pipe dream and a figment of the imagination. It never had a chance.'
Grinney testifed on Wednesday that HealthSouth would have had to forego investments in all of the company’s other 93 hospital for 2 to 3 years to finish the digital hospital.
What a contrast this was to the hype that surrounded the announcement of Scrushy's intention to build the "digital hospital." Let me provide some samples.
ComputerWorld allowed Scrushy to wax eloquent:
Hospital chain HealthSouth Corp. and software manufacturer Oracle Corp. are teaming to build what they say is the world's first all-digital, automated hospital.
The technological features will include patient beds with display screens connected to the Internet; electronic medical records storage; digital imaging instead of traditional X-ray film; and a wireless communications network that will allow doctors, nurses and other health care professionals to securely update and access patients' medical records using handheld devices.
'This will be the hospital model for the world,' HealthSouth Chairman and CEO Richard Scrushy said in the statement. 'By creating the first automated hospital ... we will demonstrate how technology can lower health care costs, greatly reduce human errors and provide patients with the best medical care available.'
Bio-Medicine gushed:
The project will be fast tracked and hopefully completed by 2003. From the moment a patient registers at the hospital, every blood test and MRI will be recorded in a central patient record, and pharmacy visits will be tracked. All charting will be done at the patient's bedside, 'getting the nurses' back to the patient's side' and making doctors more efficient. Oracle will provide the technology that will allow Health South to improve record-keeping and patient care, officials of the two companies said in a briefing on Monday. Ultimately, they said, the improvements will reduce the overall cost of care. It was also added at the briefing that another 10 sites where the hospital can be duplicated have been identified. Its now the era of cyber hospitals!!!
Managed Care Magazine was only somewhat more measured:
The promise of HealthSouth's digital hospital is great. By planning for integration on a common platform with all suppliers involved from the start, HealthSouth is maximizing the likelihood of success.
Also, HealthSouth is attempting to make the physical facility as flexible as possible to allow for the adoption of additional new technologies as they become available.
If this hospital works, it is likely to set standards for a high level of patient care. HealthSouth is anticipating that the increased efficiency of the new facility will translate into a decrease in overall length of stay.
On the other hand, everything is still in the planning stages, and details are scarce. HealthSouth has no agreements in place with insurers. Of course, the paperless hospital evokes memories of the heralded paperless office of a generation ago — and we're still waiting.
The cutting edge can be painful. But the concept of the digital hospital, automating care and administrative operations, is so appealing, we can only hope it will succeed. Time will tell.
An article in the MIT Technology Review was just a little bit skeptical:
While others have previously failed to carry off such grand visions of high-tech medicine, the deep pockets of HealthSouth and Oracle could give them a fighting chance.
But the article's conclusion was less cautious:
Not only could electronic information management help eliminate errors, it could also eliminate two to three hours a day that nurses spend charting patient data, and dramatically improve communication between different departments. The bottom line: it could save lives.
Finally, I was able to find some discussion of the proposed "digital hospital" in a scholarly publication, in fact, in probably the most authoritative and well-read journal on health care policy in the US, Health Affairs. [Burns LR, Pauly MV. Integrated delivery networks: a detour on the road to integrated health care? Health Affairs 2002; 21: 128-143.] I would not call it gushy, but it hardly seemed skeptical:
The most radical development is the incorporation of all of these technological advances into newly designed and built 'digital hospitals.'HealthSouth, traditionally a provider of integrated rehabilitation services, has announced plans to build several digital acute care hospitals over the next decade (the first is now under way in Birmingham, Alabama). The publicity surrounding the new hospital and its partnership with Oracle not only has attracted other prominent product vendors but also has enabled HealthSouth to negotiate large discounts on all equipment supplied—in effect, lowering the cost of construction.
What are the likely prospects for this intervention, either at these beta-test
sites or diffused more generally? It is plausible (although difficult to demonstrate so far) that routine patient medical and billing records can be stored or exchanged electronically. It is less obvious that this technology should lead to changes in the cost of care or help to integrate different providers of service. Indeed, the biggest chasm to bridge may be the office systems of different physicians. Kaiser Permanente is reportedly struggling to develop a clinical information system that covers its thousands of physicians and other clinicians. The (as yet undocumented) benefits will likely depend on the ability to harness technological interventions with managerial innovations and interorganizational networks, in effect creating 'socio-technical systems of care.'
So we have gone from "the hospital model for the world," with great "promise," which "could save lives," proclaiming the "era of cyber hospitals," to a "pipe dream," just the shell of half-finished building.
So I wonder, if one were to identify every highly hyped, rapidly spun, magic new "innovation" promising to revolutionize patient care, and follow them forward in time, how many would even marginally improve health care, or provide benefits that marginally out-weighed their harms? How many would never come to be, or prove to be unworkable, useless, or even harmful?
But the short-term incentives for leaders of health care organizations push them to announce innovation after innovation, collect their bonuses and perks, and be somewhere else by the time their wondrous innovations prove to be not so good.
Keep in mind that some heavily promoted innovations, such as new pharmaceuticals, must be subject to randomized controlled trials and government approval. Yet, as perusing Health Care Renewal will show, many pharmaceutical companies have managed to make their glitzy innovations appear more efficacious and less hazardous by lavish, shrewd, and sometimes deceptive marketing, and by manipulating clinical research, and sometimes suppressing results. Medical devices are not subject to as much scrutiny. Health care information technology, and programmatic innovations by hospitals, health systems, managed care and health insurance companies can appear without any research evidence to support them.
This is why we all should be extremely skeptical of whatever new "innovations" our multi-million dollar health care CEOs and their cronies are hawking these days.
The Coronary Heart Disease Epidemic: Possible Culprits Part II
In the last post, I reviewed some of the factors that I believe could have contributed to the epidemic of heart attacks that began in the 1920s and 1930s in the U.S. and U.K., and continues today. I ended on smoking, which appears to be a major player. But even smoking is clearly trumped by another factor or combination of factors, judging by the unusually low incidence of heart attacks in France, Japan and on Kitava.
One of the major changes in diet that I didn't mention in the last post was the rise of industrial liquid vegetable oils over the course of the 20th century. In the U.S. in 1900, the primary cooking fats were lard, beef tallow and butter. The following data only include cooking fats and spreads, because the USDA does not track the fats that naturally occur in milk and meat (source):
Animal fat is off the hook. This is the type of information that makes mainstream nutrition advice ring hollow. Let's see what happened to industrial vegetable oils in the early 1900s:
I do believe we're getting warmer. Now let's consider the composition of traditional American animal fats and industrial vegetable oils:
It's not hard to see that the two classes of fats (animal and industrial vegetable) are quite different. Animal fats are more saturated (blue). However, the biggest difference is that industrial vegetable oils contain a massive amount of omega-6 (yellow), far more than animal fats. If you accept that humans evolved eating primarily animal fats, which is well supported by the archaeological and anthropological literature, then you can begin to see the nature of the problem.
Omega-6 and omega-3 fats are polyunsaturated fatty acids that are precursors to a very important class of signaling molecules called eicosanoids, which have a hand in virtually every bodily process. Omega-6 and omega-3 fats compete with one another for the enzymes (desaturases and elongases) that convert them into eicosanoid precursors. Omega-6-derived eicosanoids and omega-3-derived eicosanoids have different functions. Therefore, the balance of omega-6 to omega-3 fats in the diet influences the function of the body on virtually every level. Omega-6 eicosanoids tend to be more inflammatory, although the eicosanoid system is extraordinarily complex and poorly understood.
What's better understood is the fact that our current omega-6 consumption is well outside of our ecological niche. In other words, we evolved in an environment that did not provide large amounts of omega-6 all year round. Industrial vegetable oils are a product of food processing techniques that have been widespread for about 100 years, not enough time for even the slightest genetic adaptation. Our current level of omega-6 intake, and our current balance between omega-6 and omega-3, are therefore unnatural.
The ideal ratio is probably very roughly 2:1 omega-6:omega-3. Leaf lard is 6.8, beef tallow is 2.4, good quality butter is 1.4, corn oil is 45, cottonseed oil is 260. It's clear that a large qualitative change in our fat consumption occurred over the course of the 20th century.
I believe this was a major factor in the rise of heart attacks from an obscure condition to the primary cause of death. I'll be reviewing the data that convinced me in the next few posts.
The Coronary Heart Disease Epidemic
The Coronary Heart Disease Epidemic: Possible Culprits Part I
The Omega Ratio
A Practical Approach to Omega Fats
Polyunsaturated Fat Intake: Effects on the Heart and Brain
Polyunsaturated Fat Intake: What About Humans?
Vegetable Oil and Homicide
One of the major changes in diet that I didn't mention in the last post was the rise of industrial liquid vegetable oils over the course of the 20th century. In the U.S. in 1900, the primary cooking fats were lard, beef tallow and butter. The following data only include cooking fats and spreads, because the USDA does not track the fats that naturally occur in milk and meat (source):
Animal fat is off the hook. This is the type of information that makes mainstream nutrition advice ring hollow. Let's see what happened to industrial vegetable oils in the early 1900s:
I do believe we're getting warmer. Now let's consider the composition of traditional American animal fats and industrial vegetable oils:
It's not hard to see that the two classes of fats (animal and industrial vegetable) are quite different. Animal fats are more saturated (blue). However, the biggest difference is that industrial vegetable oils contain a massive amount of omega-6 (yellow), far more than animal fats. If you accept that humans evolved eating primarily animal fats, which is well supported by the archaeological and anthropological literature, then you can begin to see the nature of the problem.Omega-6 and omega-3 fats are polyunsaturated fatty acids that are precursors to a very important class of signaling molecules called eicosanoids, which have a hand in virtually every bodily process. Omega-6 and omega-3 fats compete with one another for the enzymes (desaturases and elongases) that convert them into eicosanoid precursors. Omega-6-derived eicosanoids and omega-3-derived eicosanoids have different functions. Therefore, the balance of omega-6 to omega-3 fats in the diet influences the function of the body on virtually every level. Omega-6 eicosanoids tend to be more inflammatory, although the eicosanoid system is extraordinarily complex and poorly understood.
What's better understood is the fact that our current omega-6 consumption is well outside of our ecological niche. In other words, we evolved in an environment that did not provide large amounts of omega-6 all year round. Industrial vegetable oils are a product of food processing techniques that have been widespread for about 100 years, not enough time for even the slightest genetic adaptation. Our current level of omega-6 intake, and our current balance between omega-6 and omega-3, are therefore unnatural.
The ideal ratio is probably very roughly 2:1 omega-6:omega-3. Leaf lard is 6.8, beef tallow is 2.4, good quality butter is 1.4, corn oil is 45, cottonseed oil is 260. It's clear that a large qualitative change in our fat consumption occurred over the course of the 20th century. I believe this was a major factor in the rise of heart attacks from an obscure condition to the primary cause of death. I'll be reviewing the data that convinced me in the next few posts.
The Coronary Heart Disease Epidemic
The Coronary Heart Disease Epidemic: Possible Culprits Part I
The Omega Ratio
A Practical Approach to Omega Fats
Polyunsaturated Fat Intake: Effects on the Heart and Brain
Polyunsaturated Fat Intake: What About Humans?
Vegetable Oil and Homicide
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