Mark Pine

Some years ago, when the toxic scoop on trans fats became known, I switched from using margarine on my bread to virgin olive oil. Trans fats, which are abundant in margarine, turned out to be worse for clogging arteries than the saturated fats in butter. And if the Italians used olive oil on bread, well hey, then it must taste good too.

It does. Virgin olive oil is more pungent than butter or margarine, but also more flavorful. It’s different from butter, but just as satisfying. And now it turns out that it might possibly protect against Alzheimer’s, a disease that I frequently worry about at my age of 64.

For decades, scientists have known that Alzheimer’s patients developed plaques in their brains composed of large clumps of the protein ß-amyloid polymerized into long fibrils. But in the last decade, researchers discovered that it’s not the clumps that cause dementia but a small component of the fibrils made of two ß-amyloid molecules. The dimers (called ADDLs, amyloid-derived diffusible ligands) insert themselves into the synapses on dendrites of neurons, bind to the receptors and disrupt signal transmission.

Now a group of researchers at Northwestern University has found that a compound in virgin olive oil called oleocanthal increases the immunoreactivity of ß-amyloid compounds, which results in faster antibody-mediated clearance from the brain. But even more significant, it alters the structure of ADDLs, which results in “decreased binding to synapses, … accompanied by significantly less synaptic deterioration.” The research was also reported by ScienceDirect yesterday.

Recently and fortuitously, I began increasing my consumption of virgin olive, following recommendations of nutritional articles about eating fewer carbs and more unsaturated oils. It won’t be a problem for me to keep doing this delicious thing.

Medicare and Medicaid are the primary payers for more than half of all hospitalizations. Private insurers pay for about one third, and 6% are uninsured.

As has been reported, the Senate may today be debating whether to include a public option in the health care reform bill. But our health care system ALREADY is mostly on a public payer plan, for inpatient services at least.

Here’s another remarkable set of statistics:

The average patient treated in a hospital in 2007 in the U.S. stayed 4.6 days, and the hospital billed that patient an average of $26,100. (More than $5,600 per day!) But the hospitals’ average cost of services to the patients was only $8,700 per patient. (Less than $1,900 per day). In the decade 1997-2007, charges and costs increased by three-quarters.

The data comes from a newly released statistical report from the Agency for Healthcare Research and Quality (AHRQ). The agency calculates the hospitals’ costs based on their charges, using a ratio derived from the accounting data they submit to the Centers for Medicare and Medicaid Services (CMS). It’s my guess that the difference between charges and costs is consumed by contractual discounts to payers—which are common, capital expenditures, and profits. The report states

Hospital charges reflect the amount the hospital billed for the entire hospital stay and do not include professional (physician) fees. The charge is generally more than the amount paid to the hospital by payers for the hospitalization and is also generally far more than what it costs hospitals to provide care.

Here are some other noteworthy items in the report (italicized), along with my comments (plain text). The report presented data for the decade 1997-2007.

• Seniors 65 or older account for one-third of all hospitalizations, even though they make up only one-eight of the population. This helps to explain why the majority of hospital admissions are paid for by the government and why Obama administration spokespeople are correct to assert that improving the system will improve care for seniors
• When patients are discharged, they increasingly continue treatment at home and in nursing facilities. Discharges to such continuing care rose in the decade by 55% and 32%, respectively. That may explain in part why hospital stays shortened slightly from 4.8 to 4.6 days in the decade. Utilization of aftercare will likely increase in the future.
• There’s bad news about infectious disease. Admissions for skin infections rose by more than four-fifths, and systemic blood infections by more than three-fifths in the decade. Costs of inpatient treatment of infectious diseases doubled in the decade and rose faster than any other category of illness. It’s likely that the increase is related to antibiotic-resistant bacteria, like methicillin-resistant Staph and virulent E. coli. It’s well-recognized that bacterial resistance has resulted from over-prescription of antibiotics and the use of the drugs in factory farms that raise chickens, hogs, and beef in close quarters.
• But there’s good news about cardiovascular disease. Although such conditions continue to be the most frequent cause of hospitalization, accounting for 16% of admissions, hospital stays for coronary artery diseases dropped almost one-third, and heart attacks declined by 15% in the decade. Cerebrovascular admissions (mostly strokes) declined 14% My guess is that more people are eating “heart healthy” diets and exercising more. Also there’s the widespread prescription of statin drugs that lower cholesterol and reduce the risks of atherosclerosis.

There’s a lot to be concerned about in the AHRQ report, but it’s heartening to end this post on this very positive item.

Growing old is no fun, of course, but one of the more disagreeable aspects of it for me has been the loss of muscle strength. I’ve noticed this since turning 60 in many little ways, but two stand out: My efforts at weight training are much harder and there’s less pay off. Compared to when I was younger, the weights I can now use are lighter, and it takes longer to put on muscle mass, as measured by how long it takes to go to the next heavier weight.

But the second problem is worse. I sprain more easily and frequently, and it takes longer to heal from the sprain. Not long ago, I injured my neck by too-enthusiastically performing an exercise called “good mornings,” during which you bow with a weight behind your neck. That happened in July, and now in late September, it still pains a little.

I used to dismissed the weakness as an inevitable part of growing old, but yesterday an article in ScienceDaily suggests a cause of this kind of old-age frailty having to do with insulin. Scientists at University of Texas Medical Branch at Galveston point to a less known function of the hormone related to muscle growth. Elena Volpi, the lead author of the report of the research in Diabetologia this month put it this way:

When you give insulin intravenously and increase the blood insulin levels to the same amount produced after a meal, you see that in young people it stimulates protein synthesis and muscle growth, while in older people it really doesn’t. But when we gave seniors double the insulin they would normally produce after eating, their muscles were stimulated like those of young people.

To test the hypothesis that this age-related difference in muscle growth is caused by insulin resistance, the scientists measured blood flow to the legs of 14 healthy elderly volunteers dosed with intravenous insulin either at a level typically seen after meals or at a supra-physiologic level twice as high. Simultaneously, they measured indices of muscle protein synthesis, amino acid consumption, and intracellular Akt/mTOR signaling, which increases during muscle growth. They found that only the high-dose group exhibited increased blood flow and muscle protein synthesis, and that group had higher Akt/mTOR signaling.

Volpi speculated that the difference is related to the vascular endothelium, cells which line the blood vessels and regulate the dilation the vessels. She said:

Having a capillary dilation induced by insulin is important, because it exposes more muscle to the nutrients and hormones and everything flows better and gets stored away better. But in even healthy older people, this dilation response doesn’t work, because they have this endothelial dysfunction.

Her current research is investigating whether drug treatment with a combination of a vasodilator and insulin can ameliorate the condition.

It makes sense that a state of decreased blood flow to muscles in elderly people could underlie muscle weakness, and that such a state might be mediated by a kind of insulin-resistance. (Especially, it make sense to me, since I have a family history of type II diabetes, a disease which results from another kind of insulin resistance.)

I wonder though about the toxicity of the treatment. Insulin administration may trigger hypoglycemia, and vasodilators may cause low blood pressure. Nevertheless, I’ll watch with interest how this research develops.

The term “consciousness” can mean various things. Online this week in Scientific American, an article describes research reported in Nature Neuroscience. The following passages from the SciAm article point to an ambiguity in the use of the term.

New research suggests that some vegetative patients are capable of simple learning—a sign of consciousness in many who failed other traditional tests. …

To decide whether patients are in a minimally conscious state (MCS), in which there is some evidence of perception, or intentional movement or have sunk into a vegetative state (VS), where there is neither, doctors have traditionally used a battery of tests and observations, many of which require some subjective interpretation, such as deciding whether a patient’s movements are purposeful—to indicate a sullied feeding tube, for example—or just random. …

Previous neuroimaging work had surprised doctors by showing that some vegetative patients, when asked to imagine performing physical tasks such as playing tennis, still had activity in premotor areas. In other patients, verbal cues sparked language sectors….

The Nature Neuroscience study, conducted in Argentina, used anesthetized patients and showed they were capable of a classical Pavlovian conditioned response, in this case, learning that a tone would be quickly followed by a puff of air to the eye causing a blink. Some anesthetized and vegetative patients developed the conditioned response, according to the article, and blinked when the tone sounded.

Whether or not capacity for Pavlovian conditioning implies consciousness may be open to debate, and the issue is further considered in the report. But I have a somewhat different interest in discussing this article: Whatever the state of the comatose patients, it isn’t normal alert consciousness; if they are conscious, it can only be to some degree. Yet the authors of both articles (in SciAm and in Nature Neuroscience) used the term “consciousness” to refer to that state. Indeed, the SciAm reporter, Katherine Harmon, wrote at the beginning of one paragraph, “even less conscious organisms, such as snails, can be conditioned to equate the stimuli.”[Italics added.] This implies she used the word to describe something that can exist in various degrees.

Yet at another point in the report, Harmon noted that one of the Nature Neuroscience authors made a statement that implies consciousness is either present or absent. Quoting the scientist, she wrote, “Either the patients “‘have consciousness or maybe the test is wrong.’” In a posting in August, I described a similar confusion about consciousness in the writings of another SciAm reporter, Christopher Koch. He used the word to refer both to an all-or-nothing phenomenon and a phenomenon existing in various degrees.

The core confusion, I suspect, lies in blurring the difference between two concepts: (1) the state of being alert and attentive, and (2) the capacity for consciousness at all. The former is a narrow idea that refers to the locus and extension of a person’s consciousness at a particular moment. The second is a broad notion that refers to a person’s fundamental nature or being. When I use the term, I usually mean the latter, since I usually focus on consciousness itself.

The difference between attention—consciousness at one moment—and consciousness itself is not only a frequent source of confusion, but also a question of fundamental importance. In colloquial speech, we frequently refer to some idea as being unconscious or out of consciousness. The phrase seems almost a contradiction of terms, since if it is an idea, how can it be unconscious?

What neurophysiological state might correspond to an idea being out of consciousness?

The SciAm report suggests a possibility. It describes recent efforts to study vegetative patients with functional MRI scanners. Harmon wrote of this effort:

That fMRI findings of cognitive processes in vegetative patients have been trickling in recently leads John Whyte, the principal investigator at the Neuro-Cognitive Rehabilitation Research Network, who wasn’t involved in the [Argentine] research, to question the designation system itself. It may be that “there is a firm line” between vegetative and minimally conscious patients, “but our tools are too crude to tell us who is on which side of the line,” he says. Or it may be that categories of consciousness are not so easy to define. “It seems quite plausible that people can have neurocircuits that are capable of doing something and [others] that are not.”

Whyte is making the case for the possibility of consciousness existing in various degrees. But he elaborates a bit, suggesting that neurocircuits in the brain can operate independently. In vegetative a patient who exhibits the capacity for conditioned learning, it may be that the cluster of neurons executing that function is conscious. But the consciousness of that functional circuit may be disconnected and out of communication with other regions of the brain.

I’ve posted before about the intimate connection of communication and consciousness. In my view, communication and consciousness are much the same thing. For instance, imagine if you will a patient with many distinct functional centers of the brain each operating separately, performing their particular operations, but the do not communicate with each other.

I believe that such a patient would appear comatose. If communication between centers of the brain were severely disrupted, the patient might appear vegetative. If communication were present to some limited degree, the patient might seem minimally conscious.

I think it would be reasonable to describe each distinct brain center as conscious within itself, but the global brain would not be conscious as a functional whole. Partial conscious could perhaps be defined in terms of the amount of communication between separate functional centers of the brain.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) said “I don’t want to use a word like ‘breakthrough.’” He was quoted in the NY Times.

But back in the mid-1980, as I remember, after the discovery and identification of the AIDS virus HIV, researchers were confidently predicting that in a few years, we would have a vaccine to prevent the wasting, lethal scourge. That was a quarter century ago, and 12 years since President Clinton set a national goal of developing an AIDS vaccine within a decade.

Attempts to develop a vaccine have been stymied by HIV’s ability to evolve and change, and also because the virus invades and destroys the body’s T-cells, the very cells that defend against viruses.

In the results of a clinical trial announced yesterday, anti-HIV efficacy was only one-third, i.e., the percent of subjects who contracted an HIV infection after the vaccine was one-third less than the percent who got the virus after receiving the placebo. But even so, the limited success is occasion for rejoicing. At last something has worked to prevent catching the infection.

The clinical trial, designated RV 144, was conducted in Thailand by the U.S. Army and the Thailand Ministry of Public Health. Sixteen thousand healthy non-infected volunteers received either the vaccines or placebos starting in 2003 and ending in 2006. Afterward, the subjects were tested for HIV every six months for three years.

Actually, the trial didn’t test one vaccine but two, the first administered as a primer dose, the second as a booster.

The primer, which simulates an infection and provokes an immune response, is a modified bird virus for canarypox that can’t harm humans. The virus has been modified to carry copies of HIV genes and produces HIV proteins when administered to humans. The booster vaccine contains a synthetic surface protein of the HIV virus.

According to the Times article, scientists are puzzled by the results of the trial. The don’t understand why, if the vaccine works in one-third of the subjects, it doesn’t at least stimulate some immunity—even if it’s not protective—in the other patients. But among all the subjects who contracted HIV after vaccination, the number of virus particles in the blood was the same whether they received the vaccines or the placebo.

But the scientists don’t even understand why the vaccine works at all, since the vaccines administered alone haven’t worked in previous clinical trials.

As tantalizing as these questions are, discoveries that generate more puzzles are the rule in science. The main thing now is that something has worked, and that gives the scientists something to work on—to understand what’s going on and to improve the effectiveness of the treatment.

Last evening, Senate Democrats had a “rollicking brawl” over the $80 billion deal between the White House and PhRMA, the big drug lobby, according to the NY Times. Sen. Ben Nelson proposed an amendment to the health care bill being marked up in the Finance Committee today. His proposal would require $86 billion from the drug companies, essentially undoing the deal.

The Washington Post reported that several senators stoked tensions by calling for raising rebates that drug companies must return to the government from money for Medicaid patients, suggesting that the $86 billion in the Nelson amendment would come from Medicaid payments to the companies for drugs.

Last June, White House officials trumpeted a “historic agreement to lower drug costs” with PhRMA. It was part of the $80 billion deal, and it brought the pharmaceutical companies on board the health reform train the White House wanted to get rolling. But the terms of the deal aren’t entirely clear.

When the deal was announced, the Times reported that about $30 billion would go for 50%-off drug discounts to seniors caught in the “doughnut hole,” the gap in the Medicare prescription drug benefit between $2,700 and $6,100 in yearly drug costs. The remaining $50 billion in the agreement would come in unspecified future concessions over 10 years.

But because the government pays nothing for drugs for seniors in the hole, it accrues no benefit from that part of the agreement. And one wonders what the Obama administration has given up to the companies to get them to come aboard.

One possibility is that the administration may agree to forebear from prohibiting a common industry practice mentioned in the article in June. The companies often protect their brand-name drugs from generic competition when the drugs go off patent by paying generic manufacturers to delay bringing the cheaper drug equivalent to market. Even a six-month delay can yield a company billions in revenues from a popular drug. Previously, the President had criticized the industry practice, and members of Congress had proposed banning it.

Another possibility could be that PhRMA may have sought agreement to extend the ban, passed by Congress in 2003, that prohibits the government from negotiating with drug companies over drug prices charged to Medicare plans, setting drug prices, or establishing a uniform list of covered drugs. The proscriptions have been a financial boon to the PhRMA companies.

It seems to be a question of morality. The rich, industrialized nations of the world, like the U.S. and European countries, have ordered hundreds of millions of doses of swine flu (H1N1) vaccine from manufacturers. Effectively, the nations have bought the entire vaccine supply—at least of the first lots to be administered starting next month. But that will leave little for third world nations, which can’t pay top dollar and didn’t have the public health agencies or funding to order the vaccine early this year. What will happen to their people?

One way of dealing with the problem would be to add a substance called an adjuvant to doses of the vaccine. Adjuvants stimulate the immune response, so that less vaccine is required to attain immunity. If adjuvants were added to the H1N1 vaccine, according to an article in today’s NY Times, perhaps four times as many doses could come from the supplies, leaving more for use in poor nations.

A World Health Organization official has argued for doing that, and Canada and some European nations have decided to use adjuvanted vaccine. But our F.D.A. has denied permission to use adjuvants in vaccine administered in the U.S. because of potential safety issues. While there’s no evidence that the adjuvanted H1N1 vaccine would be more toxic, according to an agency official, it’s safety is less certain than that of the unadjuvanted vaccine, which was tested in large clinical trials this summer.

So is America wrong? Are we being selfish, hogging the world vaccine supply just to make absolutely certain the vaccine given to our own people doesn’t cause any serious adverse reactions? But meanwhile, the people in the poor countries of the world are left to suffer and die from the flu, which is expected to spread around the northern hemisphere this Fall and Winter.

The dilemma is made thornier because at least one vaccine manufacturer, Novartis, has produced an adjuvanted vaccine to seasonal (ordinary flu) since 1997, and according to the article, the company says 40 million doses have been administered in Europe without problems. So there is safety data on an adjuvant in flu vaccines.

In essence the American position rests on two geeky, technical fine points:
(1) the particular combination of the Novartis adjuvant and the H1N1 vaccine has not been tested in a clinical trial, and (2) according to Anthony Fauci, head of the National Institute of Infectious Diseases, the Novartis vaccines have been used mostly in older people, and there’s less data about the safety of the product in children, young adults and pregnant women, who are scheduled to get the first doses of the vaccine.

So who is right, the American officials or those at the WHO?

In my view, it is a moral question, but it’s not the one I asked at the beginning of the post. The principle involved is whether a medication should be used in treatment without adequate testing to establish both its safety and effectiveness. It’s not a question of whether more vaccine should be given here or more should be available elsewhere. It’s whether untested vaccine should be given anywhere at all.

Without prior testing of the combination of H1N1 + Novartis adjuvant we don’t know whether it’s safe—and we don’t truly know whether it’s effective. Treating without testing means making guesses, which can very often be wrong.

Too many people both in American and around the world—including many young healthy people and many fetuses—would receive the vaccine. If there were a problem, it could affect people in the third world as often as Americans.

Modern medicine has advanced because of adherence to the principle of evidence-based medicine. Treatment decisions must be based on the results of prior testing. That principle lies at the core of doing medicine in a way that’s effective and safe. It’s too important a principle to sacrifice unless there’s no alternative.

In yesterday’s Business Section of the NY Times, N. Gregory Mankiw, an economics adviser to President George W. Bush, told us “Why Health Care Will Never Be Equal.” He ended the piece with this question about magic pills, adding only one more, “and who pays for them?”

It is magic that he’s wondering about, because his notion of health care is mostly an imaginary idea—widely held, perhaps, but not the reality of health and illness. Here’s his main thesis:

Imagine that someone invented a pill … call it the Dorian Gray pill, after the Oscar Wilde character. Every day that you take the Dorian Gray, you will not die, get sick, or even age. … A year’s supply costs $150,000.
… Most likely, thousands of upper-income Americans would gladly shell out $150,000 a year for immortality. Most Americans, however, would not be so lucky. Because the price of these new pills well exceeds average income … So here is the hard question: How should we, as a society, decide who gets the benefits of this medical breakthrough?

Mankiw’s bases his question on a false premise. Many years ago a teacher of medicine told me about a researcher who traced the relationship of the length of the average life span to medical advances, expecting that it would jump dramatically following the discovery of penicillin. It didn’t. In fact, life span has been lengthening linearly since 1840, when a person lived on average only 40 years. That’s long before modern improvements in medicine and surgery.

What produced the increased longevity? Most likely improvements in nutrition, sanitation, working conditions, and other broad societal advances related to health. Not pills, certainly, or even medical treatment in general.

Mankiw wrote his piece, I suspect, because he wants to make a case widely held among conservatives and the far right: Life is inherently unequal and unfair, and all the current Sturm und Drang to make health care universal is ultimately futile. The wealthy will always get better care and live longer.

The reality, however, is that the wealthy live longer, not because they are able to pay for magic pills, but because they eat better, have better sanitation, and live lives of less stress.

The point of health care reform isn’t to make hi-tech treatments available for everyone as Mankiw presupposes. Indeed, to succeed, health care must move away from paying for every new medical marvel. Instead it must pay for good health outcomes that depend mostly on life-style measures and preventive care.

People will be healthy and live long if they eat the right diet, exercise regularly, get regular medical checkups and do the time-tested things their doctor advises for their health. And that won’t cost $150,000 per year.

Do you expect your doctor to decide about your medicines based on scientifically accurate and truthful information? One big obstacle to meeting your expectation comes from the ghostwriting of articles about drugs.

In this month’s issue, the editors of PLOS Medicine are decrying “the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public.”

The journal is a publication of the Public Library of Science, which makes scientific articles publicly available online.

Pharmaceutical company executives are sometimes dissatisfied with the results of clinical trials they perform to support the approval and marketing of their new drugs. In such situations, they sometimes turn to ghostwriters to spruce up the articles they submit to medical journals—articles that are suppose to report the results of the studies objectively. Their idea is to accentuate the positive and eliminate the negative. Frequently the authorship of such “enhanced” reports is attributed to a respectable academic researcher, while the true author remains unknown.

A notorious example of this kind of thing occurred with Vioxx, Merck’s drug for arthritis, which was withdrawn from the market in 2004 for causing heart attacks. After reviewing documents obtained from Merck as part of litigation, doctors writing last year in the AMA’s journal JAMA exposed the widespread used of ghost authors in the company’s Vioxx publications:

…documents were found describing Merck employees working either independently or in collaboration with medical publishing companies to prepare manuscripts and subsequently recruiting external, academically affiliated investigators to be authors. Recruited authors were frequently placed in the first and second positions of the authorship list. …documents were found describing Merck marketing employees developing plans for manuscripts, contracting with medical publishing companies to ghostwrite manuscripts, and recruiting external, academically affiliated investigators to be authors. Recruited authors were commonly the sole author on the manuscript and offered honoraria for their participation. …This case-study review of industry documents demonstrates that clinical trial manuscripts related to rofecoxib were authored by sponsor employees but often attributed first authorship to academically affiliated investigators who did not always disclose industry financial support. Review manuscripts were often prepared by unacknowledged authors and subsequently attributed authorship to academically affiliated investigators who often did not disclose industry financial support.

The Vioxx publications in question likely played a role in promoting the medicine to doctors and spurring them to prescribe the drug to tens of millions of patients. Vioxx may have caused “the single greatest drug safety catastrophe in the history of this country or the history of the world,” according to an epidemiologist at the FDA, in his testimony to Congress in 2004. He estimated that around 100,000 Americans had suffered heart attacks as a result of taking Vioxx.

This morning, the NY Times reported that eight editors of leading medical journals have responded to Sen. Charles Grassley, who has been investigating the ghostwriting issue and asked the editors in July “whether, since 2004, the journals had taken action against any author who had failed to report the involvement of a third party in the development of a manuscript.”

The newspaper, which obtained a copy of the responses, said none of the editors reported taking action. But the article said some researchers say that the practices common and ongoing.

Sen. Grassley intends to pursue the problem, according to the paper.

The Max Baucus Health Care Bill—that’s another name you can give it, because no one else joined him in announcing it—ensures huge increases in profits for insurance companies, while it pays for them partly by increasing health costs of working families.

The Washington Post reported this morning that the plan Sen. Baucus’ proposed yesterday, which requires everyone to get health insurance or pay a penalty, would produce “30 million new customers” for health insurance companies. The article also said that health industries, including insurers, who would be subject to new fees under the bill, would get rewarded with much more money than they pay out from all the new customers.

But Baucus’ bill won’t make health insurance more affordable for all those new customers. Salon.com reported today that the upper limit on insurance charges specified in the bill would still allow that “a family of four making $88,000 could pay more than $11,000 a year in insurance costs.” Yet, if such a family decided it could not afford to buy coverage costing that much, the family might have to pay a penalty of up to $3,800 a year, according to a report in the NY Times.

Moreover, Baucus’ plan allows insurers to charge the elderly up to 5 times as much as the young, according to an article in the Huffington Post. This provision contrasts with a bill in the House of Representatives that limits premium differentials based on age to 2:1. Since the elderly are more likely to get ill, the bill would allow much higher charges for many people who are more likely to need coverage. Thus, the bill undermines the fundamental principle of insurance, which is to spread costs over a pool of people, some of whom will need to use the insurance but most of whom won’t.

Since healthy young people often don’t buy health insurance, they would be among many of the new customers the bill would produce for insurance companies by requiring everyone to buy coverage. Thus, it would guarantee a new stream of revenue from people who likely won’t need treatment. But in a doubly good deal for the companies, it would also allow them to get much more money from older people, who would thereby compensate the companies for the treatment they are more likely to need.