As a mother, I am a passionate advocate of breastfeeding and I breastfed my four children. As a clinician, though, I need to be mindful not to counsel patients based on my personal preferences, but rather based on the scientific evidence. While breastfeeding has indisputable advantages, the medical advantages are quite small. Many current efforts to promote breastfeeding, while well meaning, overstate the benefits of breastfeeding and distorts the risks of not breastfeeding, particularly in regard to longterm benefits.

As Joan Wolf explains in an article entitled Is Breast Really Best? Risk and Total Motherhood in the National Breastfeeding Awareness Campaign:

… Medical journals are replete with contradictory conclusions about the impact of breast-feeding: for every study linking it to better health, another finds it to be irrelevant, weakly significant, or inextricably tied to other unmeasured or unmeasurable factors. While many of these investigations describe a correlation between breast-feeding and more desirable outcomes, the notion that breast-feeding itself contributes to better health is far less certain, and this is a crucial distinction that breast-feeding proponents have consistently elided. If current research is a weak justification for public health recommendations, it is all the more so for a risk-based message that generates and then profits from the anxieties of soon-to-be and new mothers…

Wolf describes the problems with many studies of breastfeeding, particularly those that focus on long term outcomes:

In breast-feeding studies, potential confounding makes it difficult to isolate the protective powers of breast milk itself or to rule out the possibility that something associated with breast-feeding is responsible for the benefits attributed to breast milk. As the number of years between breastfeeding and the measured health outcome grows, so too does the list of possibly influential factors, which means that the challenge is magnifiedwhen trying to evaluate long-term benefits of breastfeeding… Breast-feeding, in other words, cannot be distinguished from the decision to breast-feed, which, irrespective of socioeconomic status or education,could represent an orientation toward parenting that is itself likely to have a positive impact on children’s health. In instances such as this, in which the exposure (breast-feeding) and confounder (behavior) are likely to be very highly correlated, confounding is especially difficult to detect. When behavior associated with breast-feeding has the potential to explain much of the statistical advantage attributed to breast milk, the scientific claim that breast-feeding confers health benefits … needs to be reexamined.

But even studies that may be biased show limited, if any, long term benefits of breastfeeding. The World Health Organization published a comprehensive review of the evidence  in 2007, Evidence on the long-term effects of breastfeeding, by Horta et al. According to the authors:

…[T]here is some controversy on the long-term consequences of breastfeeding. Whereas some studies reported that breastfed subjects present a higher level of school achievement and performance in intelligence tests, as well as lower blood pressure, lower total cholesterol and a lower prevalence of overweight and obesity, others have failed to detect such associations.

Objectives: The primary objective of this series of systematic reviews was to assess the effects of breastfeeding on blood pressure, diabetes and related indicators, serum cholesterol, overweight and obesity, and intellectual performance.

The authors reviewed the existing scientific literature on 5 specific claims.

1. Does breastfeeding leader to lower blood pressure?

The authors reviewed two meta analyses and three studies:

According to Owen et al, the association between breastfeeding and lower blood pressure was mainly due to publication bias, and any effect of breastfeeding was modest and of limited clinical or public health relevance. In spite of not being able to exclude residual confounding and publication bias, Martin et al concluded that breastfeeding was negatively associated with blood pressure. They argued that even a small protective effect of breastfeeding would be important from a public health perspective… Three large studies were published since the last review, two of which found no association and one found a protective effect of breastfeeding.

Both meta-analyses may have been affected by publication bias… Lack of control for confounding is another methodological issue, as pointed out by Martin et al…

In summary, the present updated meta-analyses show that there are small but significant protective effects of breastfeeding on systolic and diastolic blood pressure. Publication bias is unlikely to explain this finding because a significant protective effect was observed even among the larger studies. However, residual confounding cannot be excluded because of the marked reduction in effect size after adjustment for known confounders.

2. Does breastfeeding lead to lower cholesterol levels?

[N]o significant effect was observed in children or adolescents, mean cholesterol levels among adults who were breastfed were 0.18 mmol/L (6.9 mg/dl) lower than among non-breastfed subjects… [T]he observed reduction associated with breastfeeding corresponds to about 3.2% of [the] median.

3. Does breastfeeding reduce the risk of overweight and obesity?

The evidence suggests that breastfeeding may have a small protective effect on the prevalence of obesity. In spite of the evidence of publication bias, a protective effect of breastfeeding was still observed among the larger studies (>1500 participants),.. This effect seems to be more important against obesity than against overweight.

Because the great majority of the published studies were conducted in Western Europe and North America, we are not able to assess whether this association is present in low and middle-income settings.

4. Does breastfeeding lower the risk of type 2 diabetes?

Evidence on a possible programming effect of breastfeeding on glucose metabolism is sparse. Studies assessing the risk of type-2 diabetes reported a protective effect of breastfeeding, with a pooled odds ratio of 0.63 (95% CI: 0.45–0.89) in breastfed compared to non-breastfed subjects. On the other hand, two other studies failed to report an association between HOMA index, a measure of insulin resistance, and breastfeeding duration, and a study on fasting blood glucose levels was also negative. At this stage, it is not possible to draw firm conclusions about the longterm effect of breastfeeding on the risk of type-2 diabetes and related outcomes…

5. Does breastfeeding raise the level of school achievement or intelligence?

This meta-analysis suggests that breastfeeding is associated with increased cognitive development in childhood, in studies that controlled for confounding by socioeconomic status and stimulation at home. The practical implications of a relatively small increase in the performance in developmental tests in childhood may be open to debate. However, evidence from the only three studies on school performance in late adolescence or young adulthood suggests that breastfeeding is also positively associated with educational attainment.

The issue remains of whether the association is related to the properties of breastmilk itself, or whether breastfeeding enhances the bonding between mother and child, and thus contributes to intellectual development. Although in observational studies it is not possible to disentangle these two effects, the positive results from the randomized trial carried out by Lucas et al suggest that the nutritional properties of breastmilk alone seem to have an effect.

In the case of these five longterm outcomes, the existing scientific evidence shows that breastfeeding has either no benefit or a small benefit.

Adriano Canttaneo, an pediatric epidemiologist and enthusiastic supporter of breastfeeding, writing in the Journal of Pediatrics and Child Health in 2008 in The benefits of breastfeeding or the harm of formula feeding? cautions against making sweeping and unsupported claims about breastfeeding:

… We do not need to use weak and shaky arguments to convince mammals to breastfeed. What we need is effective care to let them breastfeed as much and as long as they wish.

Breastfeeding is desirable and beneficial, and we should promote breastfeeding as much as possible. However, breastfeeding advocates should not overstate the benefits of breastfeeding or overstate the risks of formula feeding. Rather, we should do whatever we can to allow women who wish to breastfeed to start and maintain breastfeeding for as long as they would like.

The primary reason that I and others favor science-based medicine, as opposed to the alternatives, is that science works. As Carl Sagan said, “Science delivers the good.” Science has other virtues – it is transparent and self-corrective also.

Recently two unrelated news items have provided an opportunity to compare a scientific vs a pseudoscientific approach to the same problem – that of communicating to patients who are locked-in.

Locked-in describes those who suffer from an injury or neurological disease that mostly paralyzes them, so that they cannot move or communicate. One scenario that leads to a locked-in state is a brainstem stroke, where patients are paralyzed below the eyes – they can only blink and move their eyes, but nothing else. Widespread trauma can lead to a similar situation. ALS, which leads to progressive loss of motor neurons, can also result in total or near total paralysis.

Traditionally communication with patients who are locked in has been limited to blinking once for “yes” and twice for “no,” or perhaps twitching a finger to indicate the same. The advent of computers has lead to more sophisticated communication, such as selecting letters by looking at them displayed on a computer screen, the subject’s choice noted by a built-in camera; or by moving a joy-stick with one finger. Physicist Stephen Hawking has managed to write books using similar methods.

But these methods are slow and cumbersome. They are invaluable to the patient, and I don’t want to diminish their importance, but the point is that there is tremendous room for improvement. The ultimate goal, of course, would be to produce real-time natural communication through either speech or writing.

Facilitated Communication

Recently the case of Rom Houben has come to media attention. He is a man in his 40’s who has been in an apparent coma for the last 23 years following a car accident. However it was recently discovered that he is not in a coma or, more precisely, persistent vegetative state as was previously diagnosed but is locked in. Sometime during the last 23 years his brain recovered enough so that Mr. Houben regained consciousness. But he was mostly paralyzed by his injuries and had no way of indicating he was conscious to those taking care of him.

Eventually, a neurologist, Steven Laureys, a specialist in disorders of consciousness, reevaluated Mr. Houben with a PET scan and a more detailed clinical assessment and found that he appeared to be conscious, and therefore locked-in. Dr. Laureys reports that, although he was unable to move his eyes or hands, he could move his toe and they were able to communicate with him in the traditional but tedious yes/no method.

Then Linda Wouters came into the picture. She is a speech therapist who uses facilitated communication (FC), a technique of holding the hand of a client who cannot communicate and “helping” them type out words on a board or computer screen. However, FC has been thoroughly studies and discredited. It turns out that alleged communication through FC is simply the ideomotor effect (subconscious movements responsible for ouija board and dowsing movements) – the facilitator is doing all the communicating, even if they are not aware of it.

Video of Wouters writing with Houben’s hand tell the tale. In some videos Houben is not even looking at the screen, and may not even be awake. Wouters claims she is detecting minute movements in Houben’s hand who is guiding her to the letters – meanwhile she is flying across the computer screen with Houben’s hand. Her claims are implausible to the point that they should be rejected, barring rigorous and solid evidence to substantiate them, which is lacking.

The claims of FC are implausible, and the scientific evidence demonstrates strongly that FC does not work – it is a sad self-deception. The FC claims of Wouters are highly implausible, and the video evidence strongly suggests that she is doing all the communicating, not Houben.

What this means is that Wouters, with FC, has stolen Houben’s ability to communicate with the world. Far from providing a method of communication to a person who is locked-in, it has robbed that person of any hope of communicating, and has also inflicted a cruel fiction on them and their family. If what we strongly suspect about FC in this case is true, then Wouters is now communicating in Houben’s name.

That is the legacy of FC, a disproved method that has descended into the abyss of pseudoscience.

Brain Machine Interface

By contrast, there are those who are trying to use science to truly give the ability to communicate to those who have lost it through neurological disease or injury.

Current methods for communicating with the paralyzed primarily involve exploiting what little voluntary muscle activity they have (whether in the eyes, hands, or feet) in order to control a computer to produce words. However, some paralyzed patients lack even the minimal motor activity necessary to control such devices.

Another option is to use brain-wave measurements (electroencephalogram – EEG – measurements) to control a communication device. This could theoretically allow for a person with zero motor function to communicate by thoughts alone.

There has been steady progress in brain machine interfaces (BM() in the last decade. They involve using scalp surface electrodes, or electrodes implanted on or in the brain itself, to read the electrical signals from the brain. Those signals are then interpreted by a computer and sorted into one of a few distinct states. Computer software can then use those states to designate different letters, move a cursor around a screen, or operate equipment.

The key features of such systems are the number of different states that can be distinguished and the accuracy of the computer’s interpretation. So far such systems can only distinguish a small number of states (3-4), require extensive training, and have accuracies in the 60-90% range.

Like many new technologies, this is modest, and not any better than motor controlled systems (for those who have any motor control). It is often the case, however, that new technology does not have any advantage over older but more mature technology, except that it has more potential to improve in the future.

Recently another team has published the results of their research with BMI. A team led by Frank Guenther at Boston University have implanted electrodes in the speech area of the brain of a man who is locked in. These electrodes connect to radio transmitters which send signals to the external receiving device – so there is no need to have any wires going through the skin (a setup for infection). The implanted transmitters can be recharged through an external coil.
The computer that receives the signals interprets them as intended speech, and then makes sounds based upon its interpretation. The patient can then use the sounds as feedback, to fine tune their control.

They have now published their initial results. The patient has been trained to produce three distinct vowel sounds with his mind alone. This is an important proof of concept, but is very modest in practice. It is not sufficient for speech communication.

Other researchers have achieved similar results – distinguishing just a few states. So far it seems like the most practical application is moving a cursor across a screen. Up, down, left, and right are all that is needed in order to land the cursor on the desired letter or word.

Guenther and his team hope to increase the number of electrodes and therefore the precision of their system, to add more phonemes to its repertoire. They optimistically project that within 5 years their system will allow for some type of speech. We’ll see. I have learned to be skeptical of the 5 year optimistic projections of researchers – essentially they are saying that they will make impressive progress within the next funding cycle.

But that aside, this approach have obvious potential and progress is being made. Whether it is in 5 years or 20 or 50, progress is encouraging and it is likely we will cross significant functional thresholds in the future.

Or maybe, before this approach has a chance to mature, it will be supplanted by some other method that no one has thought of yet. The science will take time to work itself out.

Conclusion

The differences between FC and BMI are glaring. FC takes place all in the mind of the facilitator, who claims to have a highly developed skill to interpret movements that no one can see or detect. The claims are unbelievable, were made prior to meaningful research, and persist after they have been shown to be false by rigorous science.

BMI, on the other hand, is following a slow and steady research path with transparency. The claims that are being made are cautious and responsible. Sure, researchers are optimistic about the potential of their research – we expect that from researchers who need to be constantly on the prowl for competitive funding. But the only claims that matter are those they publish in the peer-reviewed literature, and they are dry and precise.

The bottom line is that getting the science right is what matters. Doing good science will help patients who are locked in. Pseudoscience will only exploit and further victimize them.

We owe it to them to remain dedicated to quality science as the standard of care in medicine.

Note: This is a slightly modified version of an article that was published in the magazine Skeptical Inquirer, Volume 34, No. 1, January/Februrary 2010. It is reprinted here with the kind permission of the Committee for Skeptical Inquiry.

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Chiropractors, homeopaths, naturopaths, acupuncturists, and other alternative medicine practitioners constantly criticize mainstream medicine for “only treating the symptoms,” while alternative medicine allegedly treats “the underlying causes” of disease.

Nope. Not true. Exactly backwards. Think about it. When you go to a doctor with a fever, does he just treat the symptom? No, he tries to figure out what’s causing the fever and if it’s pneumonia, he identifies which microbe is responsible and gives you the right drugs to treat that particular infection. If you have abdominal pain, does the doctor just give you narcotics to treat the symptom of pain? No, he tries to figure out what’s causing the pain and if he determines you have acute appendicitis he operates to remove your appendix.

I guess what they’re trying to say is that something must have been wrong in the first place to allow the disease to develop. But they don’t have any better insight into what that something might be than scientific medicine does. All they have is wild, imaginative guesses. And they all disagree with one another. The chiropractor says if your spine is in proper alignment you can’t get sick. Acupuncturists talk about the proper flow of qi through the meridians. Energy medicine practitioners talk about disturbances in energy fields. Nutrition faddists claim that people who eat right won’t get sick. None of them can produce any evidence to support those claims. No alternative medicine has been scientifically shown to prevent disease or to cure it. If it had, it would have been incorporated into conventional medicine and would no longer be “alternative.”

Are these practitioners treating the underlying cause, or are they simply applying their one chosen tool to treat everything? Chiropractors treat every patient with chiropractic adjustments. What if a doctor used one treatment for everything? You have pneumonia? Here’s some penicillin. You have a broken leg? Here’s some penicillin. You have diabetes? Here’s some penicillin. Acupuncturists only know to stick needles in people. Homeopaths only know to give out ridiculously high dilutions that amount to nothing but water. Therapeutic touch practitioners only know to smooth out the wrinkles in imaginary energy fields. They are not trying to determine any underlying cause: they are just using one treatment indiscriminately.

How do you define “cause”? We don’t know what “causes” gravity, but we understand enough about how it works to overcome it with elevators, airplanes, and rockets to the moon. We may not know what ultimately “causes” asthma, but we know enough about the causes of airway constriction and inflammation to devise effective treatments.

Let’s take a simple example: strep throat. The symptom is throat pain. Doctors don’t just treat the pain – they do a throat culture, they determine that a strep infection is causing the pain, and they treat the infection with an antibiotic. But what caused the strep infection? The body had to host the bacteria and respond to their presence by developing symptoms; the bacteria had to be capable of multiplying in the human body. The patient had to be exposed to another person who had a strep infection, who in turn had caught it from someone else – involving a chain of social and epidemiologic causes. The bacteria had to evolve from ancestor bacteria and the human from ancestor animals. In order for the life to develop, the circumstances on the early Earth had to be propitious. Keep going. The Earth had to have formed and cooled. Stars had to have created the necessary carbon, nitrogen, and other elements that were not present in the early universe. Keep going, and you will end up saying these words from the theme song of a popular TV show: “It all started with the Big Bang.” If you really want to be picky, you could go one step further and say the real cause was whatever caused the Big Bang. (But what caused that cause? Turtles all the way down?)

So you see, “cause” involves a chain of causation and there can even be several simultaneous causes. “Cause” can mean pretty much anything you want it to. But however you look at it, doctors definitely do not “just treat symptoms.”

Philosophy has studied causation. Aristotle said everything had four causes: material, formal, efficient, and final. And he introduced complications: proper (prior) causation and accidental (chance) causation. Potential or actual, particular or generic. Reciprocal or circular causality as a relation of mutual dependence or influence of cause upon effect. The same thing as the cause of contrary effects when its presence and absence result in different outcomes. He recognized that the subject of causation was complicated.

Alternative providers are more “simple” minded. They often claim to know the one true cause of all disease. That is curious, because medical science defines several categories of causes falling under the mnemonic VINDICATE:

V – Vascular
I – Infectious/inflammatory
N – Neoplastic
D – Drugs/toxins
I – Intervention/iatrogenic
C – Congenital/developmental
A – Autoimmune
T – Trauma
E – Endocrine/metabolic.

And sometimes more than one cause is involved: a traumatic injury gets infected. Where science finds complexity, alternative medicine imagines simplicity. As H.L. Mencken said:

For every complex problem, there is an answer that is clear, simple—and wrong.

Some homeopaths claim to treat “genetic” illness, tracing its origins to 6 main genetic causes: Tuberculosis, Syphilis, Gonorrhoea, Psora (scabies), Cancer, Leprosy. Bet you didn’t know tuberculosis was genetic! Neither did I. Science classifies all these as infectious except for cancer, which is neoplastic. Homeopathy disregards science and redefines “genetic” to suit its own inscrutable purposes.

Science finds many causes for disease and sometimes more than one cause for a given disease. Pseudoscience has identified the one true cause of all disease – many times. I did an Internet search and found the following 69 one causes of all disease. This is not an exhaustive list but rather an exhausted list (I stopped when I got tired of searching).

Toxemia
Subluxations
Oxygen deficiency
Psora
“Fearful, tight and negative minds”
Obstruction of ch’i along the meridians
Refined sugar
“Fault of awareness”
Grains in the diet
False beliefs and fears
“Imbalance”
Ama due to aggravated doshas
Stress
Anger
Modern medicine
Some morbid agent, producing irritation and inflammation
Arrogance
A “non-perceivable but very real attachment to the material aspect of creation”
Inadequate nutrition
A congested colon
“All disease is a learned experience which we can un-learn.”
“All illness is in our minds,” and we can cure it with faith in God, meditation, or whatever.
Spiritual vital force and its dynamic derangement
Holding on to energy within the physical, emotional and spiritual bodies that is not in harmony with us
Impairment of movement of the bones of the skull
Bad health habits
Nerves too tense or too slack
God
Lack of life
Witchcraft
Miasms
Poor sanitation
A shock experience that catches us completely off guard
Cellular memories
An excess or insufficiency of nervous tension
Poor digestion
Weak digestive fire
Exogenous toxins
Morbid matter
An unbalanced life style
Disharmony in the equilibrium of Yin and Yang
A breakdown of the immune system
A weak “immine” system
Malnutrition
Free radicals
An imbalance of electrons in the cellular atoms
Emotion
Sin
Food abuse
Allergies
Ignorance of reality
Dis-ease on any level (physical, emotional, mental, soul or spiritual) is incorrect vibratory rate(s), patterns which are not appropriate, or blocked energy pathway(s) within or between the various levels of existence
Repletion
The blood
Morbid humors
Poisonous chemicals
Emotional trauma
“Allurement” of the mind by sense objects and its “willfulness” in gratifying these desires
Toxic metals
Cold
Blocked nerves
Our inability to adapt
Overeating
Poverty
Food acidity
Violation of natural law
Liver flukes
Breaking taboos

And my favorite: “the United KKK States of America is the root cause of all disease…”

It never seems to bother them that others have found different one true causes. In his book Voodoo Science, Bob Park describes a press conference following a meeting to discuss government funding for alternative medicine research:

Perhaps the strangest part of the press conference consisted of brief statements by individual members of the editorial review board of what they saw as the most important issues for the Office of Alternative Medicine. One insisted that the number-one health problem in the United States is magnesium deficiency; another was convinced that the expanded use of acupuncture could revolutionize medicine; and so it went around the table, with each touting his or her preferred therapy. But there was no sense of conflict or rivalry. As each spoke, the others would nod in agreement. The purpose of the OAM, I began to realize, was to demonstrate that these disparate therapies all work. It was my first glimpse of what holds alternative medicine together: there is no internal dissent in a community that feels itself besieged from the outside.

When scientists encounter two mutually exclusive claims, it bothers them. They experience cognitive dissonance and try diligently to find evidence to reject one of the hypotheses and leave a winner. They eventually reach a consensus. Alternative medicine pseudoscientists don’t seem to mind cognitive dissonance. They are content to look for evidence to support their own chosen treatment while blithely disregarding competing claims. They don’t want to look for evidence that something doesn’t work. While each claims to know the one cause of disease, they don’t seem interested in looking for the one truth.

Live and let live? Create your own reality? Truth is only relative? The same thing may be simultaneously true for me and false for you? Maybe it boils down to a mutual tolerance of delusions (OK, I’ll believe that you are Jesus if you believe that I’m Napoleon). For the cynical, follow the money: “I won’t interfere with your livelihood if you don’t interfere with mine.”

I can play the cause-finding game too. I’ve discovered the one cause of all the “one cause” theories: a deficiency of critical thinking skills combined with an overactive imagination. And, of course, a failure to test beliefs using the scientific method.

Credibility alert: the following post contains assertions and speculations by yours truly that are subject to, er, different interpretations by those who actually know what the hell they’re talking about when it comes to statistics. With hat in hand, I thank reader BKsea for calling attention to some of them. I have changed some of the wording—competently, I hope—so as not to poison the minds of less wary readers, but my original faux pas are immortalized in BKsea’s comment.

Lies, Damned Lies, and…

A few days ago my colleague, Dr. Harriet Hall, posted an article about acupuncture treatment for chronic prostatitis/chronic pelvic pain syndrome. She discussed a study that had been performed in Malaysia and reported in the American Journal of Medicine. According to the investigators,

After 10 weeks of treatment, acupuncture proved almost twice as likely as sham treatment to improve CP/CPPS symptoms. Participants receiving acupuncture were 2.4-fold more likely to experience long-term benefit than were participants receiving sham acupuncture.

The primary endpoint was to be “a 6-point decrease in NIH-CSPI total score from baseline to week 10.” At week 10, 32 of 44 subjects (73%) in the acupuncture group had experienced such a decrease, compared to 21 of 45 subjects (47%) in the sham acupuncture group. Although the authors didn’t report these statistics per se, a simple “two-proportion Z-test” (Minitab) yields the following:

I won’t repeat everything from that post; rather, I’ll try to amplify the central problem of “frequentist statistics” (the kind that we’re all used to), and of the P-value in particular. Goodman explained that it is logically impossible for frequentist tools to “both control long-term error rates and judge whether conclusions from individual experiments
[are] true.” In the first article he quoted Neyman and Pearson, the creators of the hypothesis test:

…no test based upon a theory of probability can by itself provide any valuable evidence of the truth or falsehood of a hypothesis.

But we may look at the purpose of tests from another viewpoint. Without hoping to know whether each separate hypothesis is true or false, we may search for rules to govern our behaviour with regard to them, in following which we insure that, in the long run of experience, we shall not often be wrong.

Goodman continued:

It is hard to overstate the importance of this passage. In it, Neyman and Pearson outline the price that must be paid to enjoy the purported benefits of objectivity: We must abandon our ability to measure evidence, or judge truth, in an individual experiment. In practice, this meant reporting only whether or not the results were statistically significant and acting in accordance with that verdict.

…the question is whether we can use a single number, a probability, to represent both the strength of the evidence against the null hypothesis and the frequency of false-positive error under the null hypothesis. If so, then Neyman and Pearson must have erred when they said that we could not both control long-term error rates and judge whether conclusions from individual experiments were true. But they were not wrong; it is not logically possible.

The P Value Fallacy

The idea that the P value can play both of these roles is based on a fallacy: that an event can be viewed simultaneously both from a long-run and a short-run perspective. In the long-run perspective, which is error-based and deductive, we group the observed result together with other outcomes that might have occurred in hypothetical repetitions of the experiment. In the “short run” perspective, which is evidential and inductive, we try to evaluate the meaning of the observed result from a single experiment. If we could combine these perspectives, it would mean that inductive ends (drawing scientific conclusions) could be served with purely deductive methods (objective probability calculations).

These views are not reconcilable because a given result (the short run) can legitimately be included in many different long runs…

It is hard to overstate the importance of that passage. When applied to the acupuncture study under consideration, what it means is that the observed difference between the two proportions, 26%, is only one among many “outcomes that might have occurred in hypothetical repetitions of the experiment.” Look at the Minitab line above that reads “95% CI for difference: (0.0642303, 0.456982).” CI stands for Confidence Interval: in the words of BKsea, “in 95% of repetitions, the 95% CI (which would be different each time) would contain the true value.” We don’t know where, in the 95% CI generated by this trial (between 6.4% and 45.7%), the true difference lies; we don’t even know that the true difference lies within that interval at all (if we did, it would be a 100% Confidence Interval)! Put a different way, there is little reason to believe that the “center” of the Confidence Interval generated by this study, 26%, is the true proportion difference. 26% is merely a result that “can legitimately be included in many different long runs…”

Hence, the P-value fallacy. It is that point—26%—that is used to calculate the P-value, with no basis other than its being as good an estimate, in a sense, as any: it was observed here, so it can’t be impossible; when looked at from the point of view of whatever the true proportion difference is, it has a 95% chance of being within two standard deviations of that value, as do all other possible outcomes (which is why we can say with ‘95% confidence’ that the true proportion is within two standard deviations of 26%). You can see that the CI is a better way to report the statistic based on the data, because it doesn’t “privilege” any point within it (even if many people don’t know that), but the CI will also steer us away from being wrong only in “the long run of experience.” CIs, of course, will be different for each observed outcome. The P-value should not be used at all.

Now let’s look at a graph from the acupuncture report:

Hmmm. I dunno about you, but at first glance what I see are two curves that are pretty similar. They differ “significantly” at only two of the six observation times: week 10 and week 34. Why would there be a difference at 10 weeks (when the treatments ended), no difference at weeks 14 and 22, and then suddenly a difference again? Is it plausible that the delayed reappearance of the difference is a treatment effect? The “error bars” don’t even represent what you’re used to seeing: the 95% CI. Here they represent one standard deviation, not two, and thus only about a 68% CI. Not very convincing, eh?

OK, I’m gonna give this report a little benefit of the doubt. The graph shown here is of mean scores for each group at each time (lower scores are better). That is different from the question of how many subjects benefited in each group, because there could have been a few in the sham group who did especially well and a few in the ‘true’ group who did especially poorly. It is bothersome, though, that this is the only graph in the report, and that the raw data were not reported. Do you find it odd that the number of ‘responders’ in each group diminished over time, even as the mean scores continued to improve?

Just for fun, let’s see what we get if we use the Bayes Factor instead of the P-value as a measure of evidence in this trial. Now we’ll go back to the primary endpoint, not the mean scores. Look at Goodman’s second article:

Minimum Bayes factor = e^-Z²/2

At 10 weeks, according to our statistics package, Z = 2.60. Thus the Bayes factor is 0.034, which in Bayes reasoning is “moderate to strong” evidence against the null hypothesis. Not bad, but hardly the “P = 0.009″ that we have been raised on and most of us still cling to. The Bayes factor, of course, is used together with the Prior Probability to arrive at a posterior probability. If you look on p. 1008 of Goodman’s second paper, you’ll see that as strong as this evidence appears at first glance, it would take a prior probability estimate of the acupuncture hypothesis being true of close to 50% to result in a posterior probability (of the null being true) of 5%, our good-ol’ P-value benchmark. Some might be willing to give it that much; I’m not.

Now for the Hard Part

This has been a slog and I’m sure there are only 2-3 people reading at this point. Nevertheless, here’s a plug for previous discussions of topics that came up in the comments following Harriet’s piece about this study:

Science, Reason, Ethics, and Modern Medicine, Part 5: Penultimate Words

Science, Reason, Ethics, and Modern Medicine, Part 4: is “CAM” the only Alternative?

Science, Reason, Ethics, and Modern Medicine, Part 3

Science, Reason, Ethics, and Modern Medicine, Part 2: the Tortured Logic of David Katz

Science, Reason, Ethics, and Modern Medicine Part 1

A while back I wrote about rethinking how we screen for breast cancer using mammography. Basically, the USPSTF, an independent panel of physicians and health experts that makes nonbinding recommendations for the government on various health issues, reevaluated the evidence for routine screening mammography and concluded that for women at normal risk for breast cancer, mammography before age 50 should not be recommended routinely and should be ordered on an individualized basis, and that routine formalized breast self-examination (BSE) should also not be routinely recommended. In addition, for women over 50, it was recommended that they undergo mammography every other year, rather than every year. These recommendations were based on a review of the literature, including newer studies.

To say that these new recommendations caused a firestorm in the breast cancer world is an understatement. The USPSTF was accused of misogyny; opponents of health care reform leapt on them as evidence that President Obama really is preparing “death panels”; and HHS secretary Kathleen Sebelius couldn’t run away from the guidelines fast enough. Meanwhile, a society I belong to (the American Society of Breast Surgeons) issued a press release accusing the USPSTF of sending us back to the “pre-mammography” days when, presumably women only found breast cancer after it had grown to huge size (just like Europe and Canada, I guess, given that the recommendations for screening there closely mirrors those recommended by the USPSTF). Meanwhile, in the most blatant example of protecting its turf I’ve seen in a very long time, the American College of Radiology went full mental jacket with a press release that was as biased as it was insulting. Meanwhile some physicians even likened the recommendations to going back to being like Africa, Southeast Asia and China as far as breast screening goes in that he actually speculated that he’d now become very busy treating advanced, neglected breast cancers. Unfortunately, as Val pointed out, the communication of the USPSTF guidelines to the public was almost a perfect case study in how not to do it. Even though the science was in general sound and the USPSTF recommendations were in essence close to identical to what other industrialized nations do, they were communicated in just such a way as to produce maximum misunderstanding and misuse for political purposes.

Despite all the hysterical and in some cases disingenuous attacks on the new guidelines, there is one criticism that actually resonates with me because I work at a cancer center in a very urban environment with a large population of African-American women. Last week I heard on NPR this story:

Many African-American women don’t fit the profile of the average American woman who gets breast cancer. For them, putting off the first mammogram until 50 — as recommended by a government task force — could put their life in danger.

“One size doesn’t fit all,” says Lovell Jones, director of the Center for Research on Minority health at Houston’s M.D. Anderson Cancer Center. Jones says the guidelines recently put out by the U.S. Preventive Services Task Force covered a broad segment of American women based on the data available. “Unfortunately,” he says, “the data on African-Americans, Hispanics and to some extent Asian-Americans is limited.”

So while the recommendations may be appropriate for the general population, he says, it could have a deleterious affect on African-American women who appear to have a higher risk of developing very deadly breast cancers at early in life.

And this is actually true. Some of the studies used to develop the latest mammographic guidelines were performed in Scandanavian countries, and in the others arguably African-American women were underrepresented. As the article points out:

When you look at the death statistics for breast cancer in African-American women and compare them to white women, it’s stunning. Beginning in their 20s, into their 50s, black women are twice as likely to die of breast cancer as white women who have breast cancer. In older black women, cases of breast cancer decline, but the high death rates persist.

Overall, breast cancer deaths have been declining for nearly a decade (by 2 percent annually), yet deaths of African-American women have been dropping at a much slower pace. In 2009, an estimated 40,170 women will die from breast cancer. Nearly 6,000 will be African-American women.

Why this disparity exists is unclear. One potential reason is that, for whatever reason, African-American women tend to develop a more aggressive form of breast cancer known as “triple negative” cancer. What triple negative means is that the tumor is estrogen receptor negative [ER(-)], progesterone receptor negative [PR(-)], and HER2/neu negative [HER2/neu(-)]. The lack of estrogen receptor means that these tumors don’t respond to antiestrogen drugs, while the lack of HER2/neu means that they don’t respond to Herceptin. In other words, there are no targeted therapies for these tumors, only cytotoxic chemotherapy or nothing.

More importantly, there is something about the biology of these tumors that makes them more aggressive. They may respond well initially to chemotherapy but they tend to relapse rapidly and kill quickly. This subtype of tumor generally makes up around 15% of cancers among women who are not black, but among African Americans it makes up nearly 40% of tumors. This is a striking difference, and five year survival for women with triple negative cancer is considerably lower than for other types of breast cancer, particularly for young, premenopausal African-American women.

With that background, it’s not unreasonable to ask what “normal” risk for breast cancer is for purposes of recommending a program of screening mammography. On the one hand, if young African-American women are at a higher risk for breast cancer, then beginning their screening at an earlier age makes sense because it is the lower risk of breast cancer in women in their 40s that led the USPSTF to conclude that the risk-benefit ratio of mammography was less favorable in this age range. On the other hand, the more aggressive nature of breast cancer in young, premenopausal African-American women means that length bias becomes a consideration. Basically, length bias means that mammographic screening tends preferentially to pick up slower-growing, more indolent tumors. Faster-growing, more aggressive tumors tend to “pop up” between screening intervals. So, even if screening were started earlier for African-American women, it’s not clear that the benefits would be as dramatic as we might hope. Indeed, the NPR story alludes to this:

Sheppard even wonders if the old guideline of routine screening every year beginning at age 40 is good enough. “The tumors are growing fast and the intervals that we prescribe may not work,” she says. “How can we have better diagnostic tools, better screening tools that can capture the women that aren’t the average woman?”

A blogger going by the pseudonym of Isis the Scientist brought up this very issue the other day has a point when she wonders:

The other thing I wonder about is the effect these recommendations will have on the perception of health care equity. A black woman is more likely to develop aggressive cancer than a white woman before age 50, yet the USPSTF has recommended not to actively screen women less than. I wonder how this will be interpreted by that community? Black women experience a distrust of scientists performing clinical trials (second reference here), operate within a healthcare that is not always sensitive to their needs, and use mammography as a resource less frequently than white women. Will these new recommendations foster feelings of distrust and reinforce the notion that the current health care system does not adequately meet their needs?

There is a legitimate concern that the USPSTF guidelines may not be a good fit to African-American women because not only do they tend to have more aggressive disease at a younger age but they have been underrepresented in many of the large screening trials that have been used to formulate the recommended mammography guidelines. For that reason, upon further reflection I don’t think that the USPSTF guidelines should be used to determine how and when African-American women should undergo screening, as I consider them to be at a high enough risk that screening beginning at 40 makes sense.

However, as much as she did raise a valid point when she questioned whether the current mammography guidelines should apply to African-American women, still I must remonstrate with Isis and point out that the article by Nicholas Kristof that she cited in support of her speculations is dubious at best and a load of grade-A woo at worst. For example, Kristof states:

Dr. Philip Landrigan, the chairman of the department of preventive medicine at Mount Sinai, said that the risk that a 50-year-old white woman will develop breast cancer has soared to 12 percent today, from 1 percent in 1975. (Some of that is probably a result of better detection.)

What’s very important to realize is that 12% of women do not get invasive breast cancer as compared to 1% in the past. Moreover, “some of that” is not “probably” a result of better detection. Most of it is almost certainly a result of better detection of earlier breast cancer, including pre-invasive lesions like ductal carcinoma in situ (DCIS), through widespread mammography screening programs. Indeed, as this report by the American Cancer Society shows, the incidence of invasive breast cancer per 100,000 women is not increasing nearly that fast. In fact, it’s not increasing at all. On the contrary, since 2002 breast cancer incidence has actually declined, very likely due to the massive decrease in hormone replacement therapy use in the wake of the 2002 report from the Women’s Health Initiative showing that HRT doesn’t decrease cardiovascular risk but does increase the risk of breast cancer. Figure 1 in particular shows this trend, while Figure 2 shows what’s really driving the apparent increase in breast cancer diagnoses, a massive increase in the incidence of preinvasive DCIS.

We’ve known for quite some time that what’s driving this increase is nearly all mammographic screening; indeed, the article speculates that we may have finally reached the plateau in the increase of DCIS cases with the widespread use of mammographic screening over the last 20 years. That 12% figure is not just invasive cancer; it includes DCIS. While invasive cancer diagnoses are more or less stable, diagnoses of DCIS skyrocketed due to mammography. Indeed, this dovetails nicely with my earlier discussions of overdiagnosis due to mammography, because this is exactly what I’m talking about. Mammography picks up early cancers that may or may not ever threaten the life of the woman; that’s what overdiagnosis is. Moreover, overdiagnosis leads to overtreatment, as we don’t have a good handle on what percentage of DCIS lesions progress to life-threatening breast cancers if left alone. So we treat them all with surgery, nearly all of them with radiation, and most of them with Tamoxifen after surgery and radiation.

Unfortunately, in the article Kristof takes a somewhat reasonable suspicion and runs right off the dock with it into woo land, and Isis appears not to have been skeptical enough about his claims, given that she then used Kristof’s article as the basis for speculation that maybe African-American women, tending to be of lower socioeconomic status than Caucasian women, are exposed to more toxic chemicals and endocrine disruptors. Unfortunately, as Peter Lipson characterized his article, Kristof has clearly fallen for the “one true cause” fallacy so beloved of practitioners of woo, labeling endocrine disruptors such as BPA as a major environmental cause of the apparent increase in breast cancer diagnoses. Don’t get me wrong, there may well be something there in that BPA and endocrine disruptors may contribute to breast cancer, but almost certainly not to the extent that Kristof claims, even given the evidence he cites.

In addition, if there’s one thing about breast cancer, it’s that no single environmental exposure has been found to be strongly correlated with it; most of the correlations other than family history and exposure to hormone replacement therapy, including both positive and negative correlations, have been in general pretty weak. Indeed, I was recently peripherally involved in an effort to design a project to study environmental influences in breast cancer, and there are amazingly few validated environmental factors that increase the risk of breast cancer. Also, timing is very important; it may well be that it is exposure to these factors in adolescence or childhood in a “window” of susceptibility, not in adulthood, which is when they are normally studied. Right now, that’s where the current research efforts seem to be focused. In addition, breast density, which is primarily genetically determined, is a known risk factor for breast cancer as well, and investigators are actually planning to study that at our institution. All in all, it’s a hideously complicated business combining genetic and environmental factors that I am only beginning to wrap my brain around, while Kristof’s article was simplistic and alarmist in the extreme. For better information, I recommend a report from the Endocrine Society for the more sober, balanced perspective, and a report from the Breast Cancer Fund for arguments more explicitly in favor of a link. More information, including the chemical industry’s viewpoint (if you’re interested), can be found here.

I firmly believe that the recommendations for how we screen for breast cancer were overdue for an overhaul. Badly. However, the USPSTF guidelines may have gone too far too fast, at least for public consumption in light of the years of urging by the government and private advocacy organizations for all women over 40 to be screened, recommendations that say that mammography before age 50 may not be particularly beneficial were a hard pill to swallow. As I think about it more, though, one big flaw in the guidelines is that there was little consideration of how changing screening recommendations would impact special populations that may be at higher risk, such young African-American women. Worst of all, the USPSTF recommendations are an example of some of the astoundingly worst science communication I’ve seen in a long time. No groundwork was laid to prepare the public; the guidelines were just announced; and the spokespeople for the USPSTF looked like deer in the headlights when they showed up in the media to defend the guidelines. Specialty groups protecting their interests such as the American Radiologial Society and its President Dr. Kopans ate them for lunch and then laughed at their discomfiture. Meanwhile high ranking government officials couldn’t distance themselves fast enough, and lawmakers and ideologues had a field day playing politics with the guidelines.

In the end, while I still think that the new guidelines are reasonable for most non-black women, after thinking about it I doubt that they should be applied to African Americans. Finally, I’m now convinced more than ever that screening will only have limited effects in decreasing mortality from breast cancer, regardless of the test used, as long as we have so poor an understanding of the aspects of breast cancer biology that govern which early cancerous lesions will progress, which will not, and which will regress. Until we do, if there were developed a test to replace mammography, the same problems of overdiagnosis and overtreatment would remain. More than ever, we need to develop an understanding of the biology of breast cancer sufficiently advanced that it permits us to develop imaging tools and biological markers that can differentiate breast cancers that will progress and those that are not going to threaten the life of the woman. At the very least we need better indicators of risk. Until we have these things, screening will remain a highly imperfect tool that doesn’t save as many lives as it has the potential to.

ADDITIONAL READING ON MAMMOGRAPHY, BREAST CANCER, AND CANCER SCREENING:

1. The early detection of cancer and improved survival: More complicated than most people think
2. Early detection of cancer, part 2: Breast cancer and MRI
3. Do over one in five breast cancers detected by mammography alone really spontaneously regress?
4. PSA – To Screen or Not to Screen
5. Are one in three breast cancers really overdiagnosed and overtreated?
6. The cancer screening kerfuffle erupts again: “Rethinking” screening for breast and prostate cancer
7. The USPSTF recommendations for breast cancer screening: Not the final word
8. The Mammogram Post-Mortem

It’s been about a year and a half since I’ve written about this topic; so I thought I’d better update the disclaimer that I wrote at the beginning:

Before I start into the meat of this post, I feel the need to emphasize, as strongly as I can, four things:

1. I do not receive any funding from the telecommunications industry in general, or wireless phone companies in particular. None at all. In other words, I’m not in the pocket of “big mobile” any more than I am in the pocket of big pharma.
2. I don’t own any stock in telecommunications companies, other than as parts of mutual funds in which my retirement funds are invested that purchase shares in many, many different companies, some of which may or may not be telecommunications companies.
3. None of my friends or family work for cell phone companies.
4. I don’t have a dog in this hunt. I really don’t.

There. That’s better. Hopefully that will, as it did last time, serve as a shield against the “shill” argument, which is among the frequent accusations I hear whenever I venture into this particular topic area. So, as I did back in 2008, I just thought I’d clear that up right away in order (hopefully) to preempt any similar comments after this post. Unfortunately, as I have known for a long time, I’m sure someone will probably show his or her lack of reading comprehension and post one of those very criticisms of me. It’s almost inevitable, either here or elsewhere. Posting such disclaimers never seems to work against the “pharma shill” gambit when I write about vaccines or dubious cancer cures. Even so, even after nearly ten years involved in skepticism and promoting science-based medicine, hope still springs eternal.

There are two reasons that I think the issue of mobile phones and cancer needs an update on our blog: First, it has been a year and a half since I last wrote about it. At that time I castigated Dr. Ronald B. Herberman, who at that time was director of the University of Pittsburgh Cancer Institute for what I viewed as fear mongering over cell phones and cancer based on at best flimsy evidence. Second, there have been two fairly high profile studies looking at whether there is a link between mobile phone use and cancer. One of these our fearless leader Steve Novella has already discussed, but there was another one that he didn’t see because it didn’t get quite as much publicity, possibly because the corresponding author is based in Korea. I will take this opportunity to discuss them both.

Over the last several years, as cell phones have become not only ubiquitous but have morphed into in essence pocket computers with Internet connections, there has developed a cottage industry of cell phone “shields” that allegedly protect people from horrible microwaves emitted by cell phones that supposedly cause cancer. These shields, of course, do nothing of the sort; objective tests of many of them show that they don’t even do a good job of blocking electromagnetic radiation emitted by cell phones. However, the data looking at the question of whether cell phones can cause some form of cancer has been mixed at best and consistent with no detectable association or possibly a very tiny association that just rises above the background noise, but even that is arguable.

One reason we have a lot of doubts over whether cell phone radiation can actually cause cancer goes back to a longtime focus of this blog and one reason why we emphasize science-based medicine rather than evidence-based medicine, namely scientific plausibility. From a biological standpoint, a strong link between cell phone use and brain cancer (or any other cancer) is not very plausible at all; in fact, it’s highly implausible. Cell phones do not emit ionizing radiation; they emit electromagnetic radiation in the microwave spectrum whose energy is far too low to cause the DNA damage that leads to mutations that lead to cancer. True, it is possible that perhaps heating effects might contribute somehow to cancer, but most cell phones, at least ones manufactured in the last decade or so, are low power radio transmitters. It is also possible that there is an as yet undiscovered biological mechanism by which low power radio waves can cause cancer, perhaps epigenetic or other, but the evidence there is very weak to nonexistent as well. Worse, as has been pointed out many times, epidemiological evidence for people who have used cell phones heavily for more than 10 years is sparse.

Moreover, it’s not possible to study the issue by randomized studies, because it is impractical to the point of being virtually impossible to randomize people into groups that do and do not use cell phones given how essential cell phones have become to most people in industrialized nations and then to follow them for the 20 years or so that it would take to identify a link. That leaves retrospective data, with all the perils and pitfalls inherent in retrospective studies. One potential approach to such a study is to formulate a simple hypothesis. If mobile phone use causes cancer, then after the widespread introduction of cell phones into a population there should be a detectable significant increase in the incidence of tumors that could potentially be due to cell phone use, particularly 10 to 20 years later. That is the hypothesis that the investigators who published recent Danish study (Deltour et al, Time Trends in Brain Tumor Incidence Rates in Denmark, Finland, Norway, and Sweden, 1974–2003) decided to examine. It is a good population to examine this question in because the populations of these countries is homogeneous, cell phone use became widespread earlier than it did in the U.S., and these countries have nationalized health systems that allow centralized collection of cancer data in national cancer registries.

The basic design of the study was as follows. Investigators examined the cancer registries of these nations for the first incidence of brain tumors in patients aged 20-79, noting this background:

Previous investigations in Denmark, Finland, Norway, and Sweden found that the incidence of glioma was relatively stable from 1983 to 1998 ( 7 ) and that the incidence of meningioma increased from 1968 to 1997, more so for women than for men (8). Time trends in brain tumor incidence after 1998 are likely to be relevant for evaluating possible associations with respect to radio frequency exposure from mobile phones after 5 – 10 years of exposure. We investigated time trends in brain tumor incidence rates in these four Nordic countries to evaluate whether trends in the incidence of brain tumor changed in Denmark, Finland, Norway, and Sweden from 1998 to 2003.

This information is important to know, because if brain tumor incidence were rising before the widespread use of cell phones, then to find a correlation that might indicate causation, there would have to be a more rapid increase in brain cancer, starting with an appropriate lag time after the use of cell phones became so prevalent, likely at least five to ten years. This is very much like the evidence for an epidemiological link between smoking tobacco and lung cancer, except that for the tobacco-lung cancer link there was a 20-30 year lag between the introduction of inexpensive, mass-marketed cigarettes and the increase in lung cancer incidence. In any case, the resultant population examined in this study was, in essence, the entire populations of these four countries, where 59,984 brain tumor cases that were diagnosed from 1974 to 2003 among 16 million adults aged 20 –79 years. They say that a picture is worth a thousand words; so here is Figure 1 from the paper:

Panels A and B present incidence rates for gliomas and meningiomas, respectively, in men; panels C and D present incidence rates for gliomas and meningiomas, respectively, in women. Circles indicate rates for those aged 20 – 39 years, squares indicate rates for those aged 40–59 years, triangles indicate rates for those aged 60–79 years, and a solid line indicates the regression curve. As described in the paper:

During this time, the incidence rate of cancers known as gliomas increased gradually by 0.5% per year among men and by 0.2% per year among women.

For cancers known as meningioma, the incidence rate increased by 0.8% among men and, after the early 1990’s, by 3.8% among women.

This more rapid change for women was driven, the researchers say, by the 60-79 year age group.

In other words, there was a slow rate of increase in these tumors that did not change in the 1998-2003 cohort. The reasons for this slow rate of increase are unclear, but because it began before the widespread insinuation of mobile phones into the population it is almost certainly not due to mobile phone radiation. One possibility that could have contributed to this is the increasing use and sophistication of imaging technology like CT and MRI, which, as the authors pointed out in the introduction, can lead to an increased apparent incidence without any changes in etiological factors through the detection of asymptomatic meningioma, for example. (Sound familiar?) In any case, there was no detectable evidence of an uptick in the incidence of these brain tumors after 1998. The lack of evidence for a change in the rate of increase of these tumors is consistent with three conclusions. Either there is no link between cell phone use and these brain tumors; the “lag time” for such an effect is greater than 5-10 years; or the effect is too small to be detected in an overall population level. One area where I will disagree with our fearless leader (somewhat) is that I don’t consider this study to be weak evidence. It is, in fact, strong evidence that, if a link between cell phone use and brain cancer exists, it is almost certainly weak and small. Add to that the biological implausibility of a link, given our current knowledge about cancer, and I remain less than impressed with the claims that cell phones cause brain cancer. I would be happy to change my mind if new evidence, either in the form of a biological mechanism being discovered that could explain how long term exposure to low energy radio signals could cause cancer or epidemiological evidence showing a clear association between cell phone use and cancer (preferably both), came to light.

Unfortunately, the second study does not qualify as either form of evidence. (How’s that for a segue?) In fact, from my perspective, it is one of the best examples of how meta-analyses can be tortured to find tenuous correlations where none probably exist. The study, which appeared in the November 20 issue of the Journal of Clinical Oncology, apparently slipped by my notice when it first appeared as an online publication on October 13. In any case, the study (Myung et al, Mobile Phone Use and Risk of Tumors: A Meta-Analysis) is, as the title says, a meta-analysis, meaning it’s a formal way of combining multiple studies that may or may not have statistically significant results on their own, that may or may not have found a correlation, and trying to see if the weight of the evidence suggests a correlation between mobile phone use and cancer. In this case, 465 articles were winnowed down to 22 articles using specific selection criteria, which were:

We included epidemiologic studies that met all of the following criteria: case-control study (to date, no randomized controlled trials and only one retrospective cohort study published in four different articles have been reported; therefore, we included only case-control studies in this study); investigated the associations between the use of mobile phones, cellular phones, or cordless phones and malignant or benign tumors; reported outcome measures with adjusted odds ratios and 95% CIs, crude odds ratios and 95% CIs, or values in cells of a 2(1)2 table (from which odds ratios could be calculated). If data were duplicated or shared in more than one study, the first published or more comprehensive study was included in the analysis.

I’ll cut to the chase right now. This meta-analysis does not–I repeat, does not–show any correlation between cell phone use and cancer, at least not in the overall results. The authors even say so:

As shown in Figure 2, the overall use of mobile phones (use v never or rarely use) was not significantly associated with the risk of tumors in a random-effects model meta-analysis of all 23 case-control studies (odds ratio 0.98; 95% CI, 0.89 to 1.07).

Let me repeat that again. The overall meta-analysis did not find any significant association between mobile phone use and tumors.

Of course, whenever an investigator does a meta-analysis and finds a result like this, he can never rest there. He has to slice and dice the data to try to find a group for which there is a correlation. There’s nothing wrong with that in and of itself. In prospective studies, post hoc subgroup analyses that were not planned in the original protocol right from the beginning are generally frowned upon because they have a high tendency to find associations that are usually spurious. I tend to look at it as being a lot like making multiple comparisons but not controlling for them. By doing a study to look at one population and a set of outcome measures but then, upon finding a negative result, going back and doing subgroup analyses, one is basically doing multiple comparisons without correcting for multiple comparisons. Anyone who’s been a regular reader of this blog should know that if one doesn’t correct for multiple comparisons, the more comparisons the higher the likelihood of finding one or more false positives.

Even so, it’s not necessarily scientifically dubious to do subgroup analyses if one looks at it as a hypothesis-generating exercise, rather than any actual conclusions. Correlations that are found may or may not be “real,” but strong correlations may be worth further investigation. What bothers me about this study is not so much that it did subgroup analysis on the populations studied, but rather how it did a sort of dubious “subgroup analysis” on the actual studies themselves:

However, a significant positive association (ie, harmful effect) was observed in eight studies ^{7,12,14-16,18,23} and one study by another group¹⁰) using blinding (odds ratio1.17; 95% CI, 1.02 to 1.36), whereas a significant negative association (ie, protective effect) was observed in 15 studies (nine INTERPHONE-related studies^{17,20-22,24-28} and six studies by other groups^8,9,11,13,19) not using blinding (odds ratio 0.85; 95% CI, 0.80 to 0.91). No publication bias was observed in the selected studies (Begg’s funnel plot was symmetric; Egger’s test, P for bias .21; Fig 3)

[...]

Subgroup meta-analyses by methodologic quality of study revealed a significant positive association in the high-quality studies (odds ratio 1.09; 95% CI, 1.01 to 1.18), whereas a negative association was observed in the low-quality studies. In subgroup meta-analyses by malignancy of tumor, no significant association was observed for malignant tumors. However, a significant negative association was observed for benign tumors. Neither the use of analog phones nor the use of digital phones was associated with the risk of tumors.

First, note that these odds ratios are barely statistically significant, ranging from 1.02 to 1.36 and 1.01 to 1.18; in other words, the 95% confidence interval barely misses overlapping with 1.0. More importantly, I was very puzzled by the way that they chose to differentiate “high” quality studies from “low” quality studies. Basically, although it is only one of the eight criteria used in the Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Case-Control Studies to evaluate study quality, for some reason the Myung et al decided to focus primarily on whether the studies were blinded or not, specifically whether the status of patient cases and controls was blinded at interview (blinded or not blinded/no description). This struck me as most curious. So studies that were blinded showed a positive association between cell phone use and brain tumors upon meta-analysis of just their results. The authors also report that their subgroup analysis demonstrated that studies of higher methodological quality (greater than or equal 7 points) also showed a positive association between cell phone use and cancer for just these studies.

So does it mean anything that lumping the studies together that are of “high quality” produces a positive result where the low quality studies don’t? Normally, I’d think that it might. After all, the studies showing the positive result are considered to be methodologically rigorous, although it should be noted that several of them individually didn’t find a significant association. In this case, I doubt it means much of anything, and here’s why. Seven of the eight “high quality” studies were all by a single group of researchers, Dr. Lennart Hardell’s group in Sweden. Whenever one group of researchers keeps finding a result that no other group seems able to replicate or that otherwise disagrees with what everyone else is finding, that’s a huge red flag for me. Remove those studies, and even the wisp of a hint of a shadow of the association between cell phone use and cancer found in this study disappears. I’d have a lot more confidence in this seeming association in “high quality” studies if the association didn’t depend upon a single researcher and if this researcher was not also known for being an expert witness in lawsuits against mobile phone companies. Don’t get me wrong; these studies could be correct, but replication is one of the checks on research in science-based medicine. If other groups can’t replicate Dr. Hardell’s work, I wonder why. Is it something about the methodology? Is it something specific about Swedes? Is it something about the population? Are there confounders unique to his work that aren’t operative elsewhere? Until I see other researchers independent of Dr. Hardell and using a variety of different analyses find the same results, I don’t have a lot of confidence in them. Even the authors acknowledge that a weakness of their study is that “we did not explore potential confounding factors in the studies by Hardell et al that reported positive results not found by other study groups.”

There was another passage in this paper that I also found most curious:

We feel the need to mention the funding sources for each research group because it is possible that these may have influenced the respective study designs and results. According to the acknowledgments that appeared in the publications, the Hardell et al group was supported by grants from the Swedish Work Environment Fund, Orebro Cancer Fund, Orebro University Hospital Cancer Fund, and so on. Most of the INTERPHONE-related studies were mainly supported by the Quality of Life and Management of Living Resources program of the European Union and the International Union Against Cancer; the International Union Against Cancer received funds for those studies from the Mobile Manufacturers Forum and the Global System for Mobile Communication Association.

I don’t know about you, but I’ve never seen a passage like this in a research paper or meta-analysis before. It stands out like the proverbial sore thumb, and I can only think that it was placed there to try to cast aspersions, representing Dr. Hardell as the exemplar of Truth, Justice, and Science while painting the studies that failed to find an association between cell phone use and cancer as hopelessly biased, the product of Big Cellular. At least that’s how it came across to me. It struck me as gratuitous.

So where do we stand now? My interpretation of the evidence thus far is that we can say with some confidence that there is no short term risk of brain cancer from cell phone use. However, after more than ten years the evidence is less clear but trends towards either no detectable risk or a very small risk that barely rises above the noise. It’s possible that there may well be a risk; it’s possible that there is hitherto undiscovered biology that provides a mechanism by which non-ionizing radiation like the radio waves from cell phones could over time induce cancer beyond ten years. Because more and more people are using cell phones over longer and longer periods of time, it’s worth studying this issue. If there is an increased risk, it may be possible to mitigate that risk by using headsets or through the design of phones that use less energy. Mobile phone technology is a relatively new technology, though, and has only been widely available since the mid-1990s. In the U.S., it didn’t become truly ubiquitous until the early part of this decade. Consequently, there hasn’t been enough lag time for us to be truly confident of studies showing little or no risk. On the other hand, it is reassuring that early studies are pretty resoundingly negative and that there really is no good biological mechanism that we have been able to find by which cell phone radiation could cause cancer. In the next 5-10 years, more studies will be done, and, over that time, I expect evidence will answer the question one way or the other.

In the meantime, it’s useful to keep things in perspective. Each and every year, there are approximately 40,000 to 45,000 fatalities due to auto collisions. Getting in a car and driving to work every day is among the most dangerous things the average person does. Yet we accept this risk because automobiles are such an incredibly useful tool in modern life; indeed, they are indispensable to most people. Cell phones are clearly in that category as well; so even if cell phones are ultimately found to increase the risk of brain cancer by, for example, 10-20% after 10-20 years, it would most likely be a risk that most people would end up living with in order to be able to use these incredibly useful devices. My personal reading of the data is that there probably isn’t a significant risk of brain tumors due to the use of cell phones, but I am not sufficiently certain to make any blanket statements. I, like everyone else, will have to wait for the evidence to settle things one way or the other.

REFERENCES:

Myung, S., Ju, W., McDonnell, D., Lee, Y., Kazinets, G., Cheng, C., & Moskowitz, J. (2009). Mobile Phone Use and Risk of Tumors: A Meta-Analysis Journal of Clinical Oncology, 27 (33), 5565-5572 DOI: 10.1200/JCO.2008.21.6366

Deltour, I., Johansen, C., Auvinen, A., Feychting, M., Klaeboe, L., & Schuz, J. (2009). Time Trends in Brain Tumor Incidence Rates in Denmark, Finland, Norway, and Sweden, 1974-2003 JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djp415

An article written by 3 chiropractors and a PhD in physical education and published on December 2, 2009 in the journal Chiropractic and Osteopathy may have sounded the death knell for chiropractic.

The chiropractic subluxation is the essential basis of chiropractic theory. A true subluxation is a partial dislocation: chiropractors originally believed bones were actually out of place. When x-rays proved this was not true, they were forced to re-define the chiropractic subluxation as “a complex of functional and/or structural and/or pathological articular changes that compromise neural integrity and may influence organ system function and general health.” Yet most chiropractors are still telling patients their spine is out of alignment and they are going to fix it. Early chiropractors believed that 100% of disease was caused by subluxation. Today most chiropractors still claim that subluxations cause interference with the nervous system, leading to suboptimal health and causing disease.

What’s the evidence? In the 114 years since chiropractic began, the existence of chiropractic subluxations has never been objectively demonstrated. They have never been shown to cause interference with the nervous system. They have never been shown to cause disease. Critics of chiropractic have been pointing this out for decades, but now chiropractors themselves have come to the same conclusion.

In “An epidemiological examination of the subluxation construct using Hill’s criteria of causation” Timothy A. Mirtz, Lon Morgan, Lawrence H. Wyatt, and Leon Greene analyze the peer-reviewed chiropractic literature in the light of Hill’s criteria, the most commonly used model for evaluating whether a suspected cause is a real cause. They ask whether the evidence shows that chiropractic subluxations cause interference with the nervous system and whether they cause disease. The evidence fails to fulfill even a single one of Hill’s nine criteria of causation. They conclude:

There is a significant lack of evidence in the literature to fulfill Hill’s criteria of causation as regards chiropractic subluxation. No supportive evidence is found for the chiropractic subluxation being associated with any disease process or of creating suboptimal health conditions requiring intervention. Regardless of popular appeal this leaves the subluxation construct in the realm of unsupported speculation. This lack of supportive evidence suggests the subluxation construct has no valid clinical applicability. [emphasis added]

While some chiropractors have rejected the subluxation paradigm, it is supported by the major chiropractic organizations and schools and is considered essential by the great majority of practicing chiropractors. In two recent studies cited in the Mirtz et al. article, 98% of chiropractors believed that “most” or “many” diseases were caused by spinal misalignments and over 75% of chiropractors believed that subluxation was a significant contributing factor to 50% or more of visceral disorders (such as asthma and colic), an implausible idea that is not supported by any evidence whatsoever. Simon Singh was sued for saying so when he correctly referred to “wacky ideas” and “bogus treatments.”

When chiropractors use spinal manipulation therapy for symptomatic relief of mechanical low back pain, they are employing an evidence-based method also used by physical therapists, doctors of osteopathy, and others. When they do “chiropractic adjustments” to correct a “subluxation” for other conditions, especially for non-musculoskeletal conditions or “health maintenance,” they are employing a non-scientific belief system that is no longer viable.

As the authors of this paper indicate, the subluxation construct must go. And without the subluxation, the whole rationale for chiropractic collapses, leaving chiropractors no justifiable place in modern medical care except as competitors of physical therapists in providing treatment of certain musculoskeletal conditions.

The absence of publicity is astounding. This study has not even been noticed by the media. Where are the sensationalist journalists who usually exaggerate the news and make up provocative headlines? They could be trumpeting “Chiropractic Is Dead!” “Chiropractors Admit They Were Deluded by False Beliefs” “Simon Singh Vindicated: Chiropractic Really Is Bogus” and so on. Chiropractors demolishing the basis for chiropractic ought to be big news.

When the news finally gets out, I predict contorted efforts at damage control. Chiropractors will claim that it is not appropriate to apply the Hill criteria in this way, and that the criteria are not a valid test of causality. That’s a straw man: not even Hill suggested that the criteria were a definitive test. They are more of a guide to thinking about causality. Edzard Ernst, the world’s first professor of complementary and alternative medicine, finds them useful. He has recently applied Hill’s criteria to neck manipulation as a cause of stroke: he found that it fulfilled all but one of the criteria for causation. (Article pending publication). Chiropractors won’t like that either.

I predict the authors of this paper will be attacked as traitors by their colleagues. And I predict my own comments will be misinterpreted as some kind of personal vendetta and I will be called ugly names. I also predict that no one will dispassionately offer acceptable scientific evidence to contradict the findings of the paper (They can’t, because there isn’t any!). The first comment (and so far the only comment) on the Chiropractic and Osteopathy website offers no counter-evidence but rather calls for not letting evidence-based protocols overshadow clinical experience.(!) The Weekly Waluation of the Weasel Words of Woo could have a lot of fun translating that statement.

If chiropractors reject the conclusions of the Mirtz et al. paper, the burden of proof falls on them to show

1.  that the subluxation can be objectively demonstrated,
2.  that it does cause interference with the nervous system, and
3.  that it does cause disease.

They have failed to do so for 114 years.

Most chiropractic research falls under the category of Tooth Fairy Science. Instead of doing good basic research to examine the subluxation construct as a falsifiable hypothesis, they blindly forged ahead, implemented it for diagnosis and treatment, and studied various aspects of its clinical use.

The chiropractic emperor has no clothes, and now even some chiropractors have realized that. This study should mark the beginning of the end for chiropractic, but it won’t. Superstition never dies, particularly when it is essential to livelihood.

We are nearing the end of the second wave of the 2009 H1N1 pandemic, and are now a few months out from the release of the vaccine directed against it.  Two topics have dominated the conversation: the safety of the 2009 H1N1 influenza vaccine, and the actual severity of the 2009 H1N1 infection.  Considering the amount of attention SBM has paid the pandemic and its surrounding issues, and in light of a couple of studies just released, it seems time for an update.

2009 H1N1 Vaccine Safety

This week the CDC released a report that evaluated the safety record of the 2009 H1N1 vaccine.  The first two months of the vaccine’s use were examined, from October 1^st through November 24^th using data from two of the larger surveillance systems monitoring the 2009 H1N1 vaccine’s safety: the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD).  This report represents the largest, and to date best, evaluation of the 2009 H1N1 vaccine’s safety profile since its initial testing and release.  The findings are reassuring.

We’ve talked about VAERS’ uses (and abuses) in the past.  Nevertheless, used properly as a surveillance tool, a “canary in a coal mine,” it can be quite helpful.  In that two-month span of time when 46.2 million doses of H1N1 vaccine were distributed, 3,783 adverse events associated with it were reported to VAERS.  204 of these events were classified as “serious,” including 13 deaths that occurred within 19 days of vaccine administration.

At first blush people may assume (unwisely) that the vaccine directly caused each of these reported events, and would thus yield an adverse event rate of 82 total adverse events and 4.4 serious adverse events per 1 million doses.  This is indeed the assumption (and mistake) made by people claiming for instance that the flu vaccine has caused X number of deaths or Y cases of Guillain Barre Syndrome (GBS).  Even taken (again, unwisely) at face value, these rates would be impressively low, particularly when compared to the risks of H1N1 infection, as we shall see later.

The story is even more reassuring once we look properly at the data.  It bears repeating that VAERS does not (nor was it meant to) establish causation, it only holds the potential to suggest a correlation.  We should also bear in mind that GBS, death, all adverse events in fact, occur at a baseline rate in the population in the absence of the vaccine (a hypothetical vaccine causing zero adverse events would still have a list of adverse events reported to VAERS reflecting the population’s baseline rates).  Thus to even determine if there is a significant correlation between the vaccine and any given adverse event, we need to determine not only how many adverse events occur in relation to the 2009 H1N1 vaccine, but the number that occur above the expected baseline.

That having been said, let’s examine the most concerning number first, the 13 reported deaths.  Each of the 13 are detailed on this chart.  It’s very much worth taking a look.  There is no discernable pattern to the ages of these unfortunate people, their underlying diseases, or their causes of death.  9 of these 13 people had significant underlying diseases, and one of them died in a car accident. Indeed, considering the population’s baseline mortality rate, it’s remarkable that only 13 people out of 46.2 million died within 3 weeks of receiving the vaccine by chance alone.  This doesn’t definitively exonerate the 2009 H1N1 vaccine from these deaths (well, we can probably safely rule out the car accident), but it certainly makes its involvement highly unlikely.

H1N1 Vaccine and GBS?

What of the concern of Guillain Barre Syndrome (GBS) following vaccine administration?  After all, at least one influenza vaccine in the last three decades has been shown to cause GBS in rare cases, and some poorly handled stories in the media have further elevated public concern.

The first two months of vaccine use saw 12 cases of suspected GBS reported to VAERS.  Investigation into these reports has confirmed four of these to be cases of GBS, four were not GBS, and the final four are still under scrutiny.

Again, these cases require context.  As the baseline rate of GBS is ~1/100,000 people per year, ~550 cases can be expected to occur in the US during the two months of this report.  These 8 likely cases of GBS in 46.2 million doses of vaccine is certainly not higher (and is in fact far less) than what one would expect to see by chance.  The VAERS database provides no reason to suspect the 2009 H1N1 vaccine has anything but chance correlation with cases of GBS.

H1N1 and Other Severe Adverse Events?

There is no correlation between the H1N1 vaccine and either GBS or death, but what of other concerning adverse events?  An evaluation of the 204 serious events reported reveals a scattershot of diseases, none of which have a signal that rises above baseline rates.

The CDC report contains a similar analysis using data from the VSD, where 438,376 doses of the H1N1 vaccine had been administered and adverse events tracked.  As with the VAERS data, no serious adverse events rose above their baseline rates.

In short, after the first two months of use and 46.2 million doses, the VAERS and VSD data fails to provide any evidence to correlate the 2009 H1N1 vaccine to any serious adverse event.  Given the seasonal influenza vaccine’s similar record over the past several decades, that the 2009 H1N1 vaccine continues to display an exemplary safety profile is not unexpected, but it is reassuring.

How Severe is 2009 H1N1?

What of H1N1’s severity?  What toll has it exacted?  The CDC has made detailed information, updated weekly, available to the public on its Fluview website.  Containing a wealth of information, there you can see 2009 H1N1’s unique and peculiar epidemiology, the unseasonable spikes in outpatient visits for influenza-like illnesses that have troubled our EDs for the last few months, and the trend of lab-confirmed influenza hospitalizations and mortality over time.

Hard numbers are also available.  As of November 28^th, at least 31,320 people in the US have been hospitalized and 1,336 have died from 2009 H1N1 since August 30^th.  The 2009 H1N1 has thus far claimed the lives of at least 250 children in between the traditional flu seasons, which is more than the two prior flu seasons combined.

This data is most helpful if viewed as the minimum confirmed impact of the disease, and as a catalogue of the most severe cases to date.  What you will not find on the Fluview site is the actual incidence of influenza infection, the total number of people infected, including minor infections.  This number is extremely valuable when trying to gauge the true severity of any infection, but fiendishly difficult to acquire.

A study published in PLoS Medicine this week contains one of the latest attempts to quantify 2009 H1N1’s severity to date.  Drawing from the data of two US cities during the initial wave of infections between April and July, they estimated that of all 2009 H1N1 infections, between 0.16-1.44% will require hospitalization, 0.028-0.239% will require ICU care, and 0.007-0.048% will die.

This study has garnered a significant amount of attention, for its estimates of severity are considerably lower (thankfully) than those made by the President’s Council of Advisors on Science and Technology in early August.  The accuracy and differences between these estimates, the inherent difficulty of determining the true incidence, severity, and future course of diseases like influenza warrants its own post, and I’ll not address this particular angle in greater depth here.

I’d like to instead reflect on what these two studies might tell us about the risks of contracting 2009 H1N1 compared to the risks of receiving the vaccine to protect against it.

On the one hand, we have a virus that has proven itself to be widespread and highly contagious, to have claimed the lives of at least 1,336 and hospitalized over 30,000.  Conservative estimates from the PLoS study place one’s risk of hospitalization if infected at ~1/625, and risk of death ~1/14,285.  Furthermore, though we have completed the second wave of the pandemic, a third wave is almost certain to come.  A small minority of the population has thus far been infected, past influenza pandemics have featured a triple peak, and we have now entered the beginning of the traditional influenza season.

On the other hand, we have an inexpensive vaccine which is an excellent match to this strain, generates an appropriate antibody response in most people (particularly those in the highest risk groups for 2009 H1N1), and after over 46 million doses has yet to be significantly correlated with any severe adverse events.

Conclusion

There are still a lot of uncertainties regarding the rest of this influenza season.  Will we have a third peak of H1N1, and if so, how severe will it be?  Will it continue to preferentially afflict the young, or will the elderly suffer a greater impact than they have to date?  How will the presence of 2009 H1N1 impact the normal flu season, will it be cumulative, or will 2009 H1N1 “crowd out” the seasonal strains?  The list goes on, and it absolutely includes the possibility that with ongoing surveillance and studies we may identify a serious but rare side effect caused by the vaccine.

As time goes on we will continue to refine our knowledge of influenza, and these questions will be answered, but it is unlikely that the big picture will significantly change.  Influenza is a virus with serious potential for harm that can be prevented by one of the safest interventions in modern medicine.  Please, particularly if you or yours are in a high-risk group, get vaccinated; I already know far too many of the names on this list.

Steve Novella whimsically opined on a recent phone call that irrationality must convey a survival advantage for humans. I’m afraid he has a point.

It’s much easier to scare people than to reassure them, and we have a difficult time with objectivity in the face of a good story. In fact, our brains seem to be hard wired for bias – and we’re great at drawing subtle inferences from interactions, and making our observations fit preconceived notions. A few of us try to fight that urge, and we call ourselves scientists.

Given this context of human frailty, it’s rather unsurprising that the recent USPSTF mammogram guidelines resulted in a national media meltdown of epic proportions. Just for fun, and because David Gorski nudged me towards this topic, I’m going to review some of the key reasons why the drama was both predictable and preventable.  (And for an excellent, and more detailed review of the science behind the kerfuffle, David’s recent SBM article is required reading.)

Preamble

In an effort to increase early detection of breast cancer, American women have been encouraged to get annual screening mammograms starting at age 40. Even though mammograms aren’t as sensitive and specific as we’d like, they’re the best screening test we have – and so with all the caveats and vagaries associated with what I’d call a “messy test,” we somehow collectively agreed that it was worth it to do them in this age group.

Now, given the life-threatening nature of breast cancer, it’s only natural that advocacy groups and professional societies want to do everything in their power to save women from it. So of course they threw all their weight behind improving compliance with screening mammograms, and spent millions on educating women about the importance of the test. Because, after all, there is no good alternative.

However, the downside of an imprecise test is the false positive results that require (in some cases) invasive studies to refute them.  And so this leaves us with 2 value judgments:

1. How many women is it acceptable to harm (with unnecessary biopsies) in order to save one life? Roughly, the answer is a maximum of 250 over 10 years (I came up with that number from the data here -  if as many as half of women receive a “false alarm” mammogram over a period of 10 years of testing, and half of those undergo an unnecessary biopsy).

2. How many tests are we willing to do (this is more-or-less an economic question) to save 1 life?  The answer is roughly 1900.

So when the USPSTF took a fresh look at the risks and benefits of mammography and recommended against screening average risk women between 40-50 (and reducing mammogram frequency to every other year for those over 50), what they were saying is that they would rather lose a few lives to save a vast number of injuries (unnecessary biopsies) and costly annual testing. In fact, their answer was that they were willing to perform 1300 mammograms to save 1 life, not 1900 (as has been our standard of care).

This value judgment is actually not, in and of itself, earth shattering or irresponsible. But it’s the societal context into which this judgment was released that made all the difference.

Timing Is Everything -Or – Why Not To Bring A Party Hat To A Funeral

First of all, the timing of the USPSTF guidelines couldn’t have been worse. The country was in the midst of trying to pass our first serious healthcare reform bill in decades (at least, the house reform bill was being voted upon the week that the USPSTF guidelines were released) and opponents of the bill had already expressed vehement concern about arbitrary government rationing of healthcare services.

Is there a more inopportune moment for a government agency to (against the commonly held views of the rest of the medical establishment) recommend reduction in frequency of a life-saving screening test for women? The fact that the vice chair of the USPSTF (Dr. Diana Petitti) said she hadn’t thought about the greater context when she scheduled the press release is quite astonishing. On the one hand, I suppose it shows that the workgroup wasn’t particularly politically biased. On the other hand, it violates Public Relations 101 so completely as to call into question the judgment of those making… er… judgments.

You Can’t Replace Something With Nothing -Or – How To Take Scissors From A Baby

Let’s just say for a moment that we all agree that mammograms aren’t the greatest screening test for breast cancer. They’re rather expensive, and wasteful. Perhaps one might even argue that in a healthcare system with limited resources, one healthy woman’s screening test is another woman’s insulin.  But – it’s all we have. And they do save lives… occasionally.

Anyone who’s seen a child pick up something harmful realizes that the only way to take it from them without tears is to replace it with something harmless. You can’t just take away mammograms from women who have come to expect it, without offering them something more sensible. If there is nothing, then I’m afraid that discontinuing them will result in considerable outrage which you may or may not wish to engage. Given the size and power of the breast cancer lobby – I’d say it’s pretty much political suicide. (And of course, after the USPSTF released their guidelines, HHS Secretary Kathleen Sebelius virtually denounced it, and congress moved immediately to create legislation to require health insurers to cover mammograms for women in their 40s-50s).

Know Your Opposition -Or- Don’t Bring A Knife To A Gun Fight

And that brings me to my next point. The breast cancer movement is one of the most powerful and successful disease fighting machines in the history of medicine. And bravo to all the women and men who made it such a visible disease. The amount of funding, research, and PR that this cancer gets is astounding – it dwarfs many other worthy diseases (like pancreatic cancer or lymphoma), and is a force to be reckoned with.

Which is why, before you undermine a cherished tenet of such a group, you take a long hard look at what you’re going to say… Because it will be shouted from the hilltops, scrutinized from every conceivable angle, and used to rally all of Hollywood, the medical establishment, and everyone in Washington to its cause. Yeah, you better be darn sure you’re “right” (whatever that means in this context) before attempting to promote a service cut back to this group.

Know Who You Are -Or- Unilateral Decision Making Is Not A Great Idea, Especially For Government

And finally, it’s important not only to know who you’re dealing with, but to know your mission in society so you can be maximally effective. The US government exists to honor the will of the people and serve its citizens. The best way to do that is to listen to them carefully, engage in consensus-building, and try to be a good steward of resources. When government behaves in ways counter to our expectations, it provokes legitimate negativity.

So, for example, when a small group of civil servants hole themselves up in a room to create guidelines that will potentially take preventive health services away from women – resulting in a larger number of deaths each year, they don’t invite input from key stakeholders, and then announce their views in the midst of a firestorm about “rationing,” you’re going to get nuclear level blowback.

Summary

The new USPSTF guidelines for mammogram screenings debacle serves as a perfect public relations case study in what not to do in advancing healthcare reform. It was the perfect storm of high profile subject, bad timing, poor argument preparation, and lack of back up planning. Though we could have had a rational discussion about the cost/benefit analysis of this particular screening test, what we got instead was the appearance of a unilateral rationing decision by an out-of-touch government organization, devaluing women to the point of death. Throw that chum in the water of human frailty and you’ll get the same result every time: a media feeding frenzy that makes you regret the moment that guideline development became a twinkle in your task-force eye.

The new mantra of midwives and their advocates is “evidence based practice.” Lamaze, the childbirth education organization has changed the name of their blog to “Science and Sensibility” emphasizing the importance of science and promising:

Lamaze education and practices are based on the best, most current medical evidence available, and can help reduce the overuse of unnecessary interventions while improving overall outcomes for mothers and babies.

But midwives and childbirth educators like Lamaze have a problem. The scientific evidence often conflicts with their ideology. They could address this problem in several ways. Midwives could modify their specific ideological beliefs on the basis of scientific evidence. Childbirth educators could question whether ideology has had an inappropriate impact on the promulgation and validation of their recommendations. Both those approaches would involve a threat to cherished beliefs. They, therefore, have taken a different approach. They’ve tried to justify ignoring scientific evidence.

As midwives Jane Munro and Helen Spiby have documented in The Nature and Use of Evidence in Midwifery, the first chapter of their book Evidenced Based Midwifery, midwives were initially enthusiastic about basing clinical practice on scientific evidence. That’s because they had long told each other that midwifery was “science based” while obstetrics was not:

At the beginning of the evidence based practice movement, much of the midwifery profession responded enthusiastically to the potential for change… Evidence based practice was seen to be offering a powerful tool to question and examine obstetric-led models of care that had dominated the previous decades. The results of such examination could have meant ’starting stopping’ the unhelpful interventions that had embedded themselves in common practice …

But it turned out that obstetrics had been based on scientific evidence all along and it was midwifery that ignored the scientific evidence in favor of ideology. Indeed, almost all practices exclusive to midwifery (as opposed to copied from obstetrics) have never been tested. They might be valuable; they might be useless; they might even be harmful. No one bothered to check before implementing them because they were based on ideology.

It has been quite a shock to midwives and childbirth educators to learn that most of their own practices have never been scientifically validated. Even worse, much of their critique of modern obstetrics flies in the face of the existing scientific evidence. As Munro and Spiby explain:

… [S]ome midwives have not been so enthusiastic [about evidence based practice], viewing the drive to create and implement evidence as a threat to their clinical freedom.

In other words, cherished ideological beliefs conflict with scientific evidence. Thus began the attack on scientific evidence.

As a first approach, midwives and childbirth educators have rejected the definition of evidence. As defined by Sackett, the founder of evidence based practice, it is “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.” That sounds objective, and evidently, objectivity is a problem. They have attempted to solve that problem by insisting that evidence can only be defined in context. “Context” in this case really means “ideology.”

Scientists see the ideology free nature of scientific evidence as one of its strengths and therefore privilege it as the ideal form of evidence. But Lomas, writing about midwifery critics of evidence, explains that they reject this privileged status:

[I]t is important that context evidence should not be viewed as any less ’scientific’. They advocate moving forward from the epistemological argument about what is ‘best evidence’ towards a ‘balanced consensus’ …

The use of the word “consensus” is illuminating. Evidence can only be evidence if it includes the opinions of midwives and childbirth educators, whether those opinions are based on science or not. Indeed, the scientific facts are merely one aspect of evidence. “Social science oriented research” and “the views of stakeholders” are supposed to have equivalent weight.

Such is the genesis of midwifery papers like Wickham’s Evidence Informed Midwifery, and, my personal favorite, Parrat and Fahy’s Including the nonrational is sensible midwifery. When the evidence does not support your claims, the use of adjuncts, including nonrational ones, will justify any beliefs.

The Parrat and Fahy paper is particularly instructive on this point. Their central claim is that the inclusion of the non-rational is midwifery “enhances safety”:

When the concept of ’safety’ is considered in childbearing it can illustrate how insensible rationality can be and how negative consequences can occur. Safety is an abstract concept because it is difficult to define and can only be considered in general terms. Rational dichotomous thought, however, provides ’safety’ with the following defining boundaries:

- ’safe’ has a precise opposite called ‘unsafe’,
- every situation/person/thing must be either be safe or unsafe,
- a situation/person/thing cannot be both safe and unsafe,and
- it is not possible for a situation/person/thing to be anything
other than safe or unsafe.

Furthermore:

…What is deemed as safe is aligned with what is rational and what is unsafe is aligned with what is irrational. As irrationality is not acceptable this essentially forces the definition of safety to be thought of as ‘true’ even though it may not fit with personal experience and all situations… As the standard birth environment is the medicotechnical environment of the hospital this is presumed to be the safest. Its ‘opposite’, the home environment, is therefore rationalised to be unsafe. To argue otherwise would define the rational person as irrational… In the purely rationalist way of thinking there is no other option except to consider that honouring the nonrational variabilities of individual bodily experience is irrational and unsafe.

The authors end with a flourish of outright stupidity:

For example, when a woman and midwife have agreed to use expectant management of third stage, but bleeding begins unexpectedly, the expert midwife will respond with either or both rational and nonrational ways of thinking. Depending upon all the particularities of the situation the midwife may focus on supporting love between the woman and her baby; she may call the woman back to her body; and/or she may change to active management of third stage. It is sensible practice to respond to in-the-moment clinical situations in this way…

This paper is but one example of a disturbing trend: many midwives and childbirth educators use the term “scientific evidence” merely as a rhetorical device, in the same way that creationism and other form of pseudoscience use the term “scientific evidence.” As Coker details in his article Distinguishing Science and Pseudoscience:

Pseudoscience appeals to the truth-criteria of scientific methodology while simultaneously denying their validity.

Similarly, midwives and childbirth educators invoke the criteria of scientific methodology while simultaneously insisting that their personal beliefs matter as much if not more.

Several weeks ago I wrote the first in a brief series of posts discussing the different types of evidence used in medicine. In that post I discussed the role of correlation in determining cause and effect.

In this post I will discuss the basic features of an experimental study, which can sere as a check-list in evaluating the quality of a clinical trial.

Medical studies can be divided into two main categories – pre-clinical or basic science studies, and clinical studies. Basic science studies involve looking at how parts of the biological system work and how they can be manipulated. They typically involve so-called in vitro studies (literally in glass) – using test tubes, petri dishes, genetic sequencers, etc. Or they can involve animal studies.

Clinical trials involve people. They are further divided into two main categories – observational studies and experimental studies. I will be discussing experimental studies in this post – studies in which an intervention is done to study subjects. Observational studies, on the other hand, look at what is happening or what has happened in the world, but does not involve any intervention.

Experimental Studies

The primary advantage of experimental studies is that they allow for the direct control of variables – in the hopes of isolating the variable of interest. Results are therefore capable of being highly reliable, although good clinical experiments are difficult to design and execute. When assessing a clinical trial here are the features to examine.

Prospective vs Retrospective

A prospective trial is one in which the treatment and the outcomes are determined prior to any intervention being done. Experimental trials are almost by definition prospective. A retrospective trial is one in which the data is gathered after the fact – taking patient records, for example, and looking at treatments and outcomes.

In a retrospective study you can try to account for variables, but you cannot control for them. It is therefore much more likely that there are confounding factors and the results are not as reliable.Also, retrospective studies can be biased by the way information is obtained – there can be a bias in the way patients are identified, for example.

Prospective trials are therefore considered superior to retrospective trials, which are at best preliminary in their conclusions.

Placebo-Controlled

Not all prospective trials are placebo-controlled, however. A non-controlled trial might identify potential subjects, give them all a treatment, and then see how they do. Such open-label single arm trials cannot control for placebo effects or experimenter biases, and again results should be considered preliminary.

Open or uncontrolled trials are not useless, however. The outcome of subjects in such trials can be compared to historical controls, and if a significant result is apparent (along with safety) can be used to justify a larger and more rigorous trial.

Controlled trials have one or more comparison groups in the trial itself – different groups of subjects receive different treatments or no treatment. All subjects can be followed in same manner. Control groups allow the experimenter to make sure that all the subjects have the same disease or symptoms, that they receive known treatments, and many variables (such as other treatments they may be receiving, severity at inclusion, age, sex, race, etc.) can be accounted for.

Controlling for variables

With controlled trials the experimenter can start to control for variables. If the question is – does treatment A improve outcome in disease X, a controlled prospective trial can attempt to isolate treatment A from other factors that may affect outcome.

One method for controlling variables is stratification – the study protocol can place subjects in different treatment groups so that the groups end up with the same proportion of different sexes, ages, races, and other known variables that may be pertinent. Stratification can control for known or obvious confounding factors.

But of course there can always be unknown confounding factors. The only way to deal with these is through randomization and large study size. If a large number of subjects are randomly assigned (once stratified for age, sex, etc.) into the different treatment groups, then any unknown variables should average out. Of course, this requires sufficient numbers – small studies are always suspect because the groups may be significantly different by chance alone.

Randomization is important because when patients select their own treatments this opens the door for selection bias. For example, sicker patients may opt for more aggressive therapy. They will do worse because they were sicker to begin with, making the more aggressive therapy look less effective.

Blinding

A randomized prospective trial can control for many variables, but the only way to control for placebo effects and the bias of the experimenters is with blinding – meaning that participants don’t know who is getting the real treatment and who is getting a different treatment or a placebo.

A single-blind study is one in which subjects do not know which treatment they are getting. A double-blind study is one in which the experimenter does not know either – until the study is done and the “code is broken.”

When subjects are blinded, placebo effects should be the same. It is often difficult, however, to fully blind subjects. Medications may have obvious side effects, and subjects who experience the side effects know they are getting active medication.

Physical interventions, like acupuncture, surgery, massage, or physical therapy, are difficult to impossible to blind. A person knows if they have been massaged or not. For these studies creative blinding techniques may need to be used. Or, “sham” procedures can be used for placebos.

Studies may also assess how successful the blinding was – by asking subject if they think they received the placebo or the treatment.

Experimenters also need to be blinded to eliminate placebo and biasing effects. This is easy for drug trials, but may be impossible for physical intervention trials. However, a study can be partially double-blinded if there is a blinded evaluator – an experimenter whose only involvement with the study is to assess the subjects, while carefully avoiding any information that would clue them in as to which treatment arm each subject was in.

But the best studies are ones in which everyone involved is completely blinded until the results are completely in.

Outcome measures

Deciding how to determine if an intervention “works” is not always trivial. Outcome measure need to be a good and reliable marker of the disease or syndrome you are following. For example, in a diabetes study, do you follow HgA1C, random glucose checks, glucose tolerance tests, end-organ damage, need for medication, or some other biological marker?

In addition to being a good marker for what you are studying, the outcome should be meaningful. Do we care if a cholesterol lowering drug lowers total cholesterol, or if it prevents heart attacks and strokes? And if it prevents heart events, does it prolong survival (or just reduces angina without affecting survival)?

Outcomes also need to be free of confounding. For example, early stroke trials looked at stroke incidence, which may seem reasonable. However, if more subjects on a treatment died of heart attacks, they would not be around to have a stroke, so the treatment reduces stroke but only by allowing more heart attacks. So stroke-free survival is a better outcome to follow.

Outcome measures also vary on how objective or subjective they are. Just asking patients how they feel is not a very reliable outcome measure. You can pseudo-quantify this by asking them to put a number on their pain or other symptoms, but it is still a subjective reports. Measuring the volume of lesions in the brain, however, is an objective outcome measure, and is therefore more reliable.

Many studies will follow several outcomes – some subjective but important, and others objective and quantifiable if an indirect marker rather than a direct outcome we care about.

Statistical analysis

I won’t go into statistics in any detail, as that is a highly technical area and any reasonable treatment would be much longer than the rest of this post. Here even medical professionals rely upon statistical experts to make sure we get it right.

But it is good to understand the basics (as long as you don’t rely upon basic knowledge – then it is easy to be fooled by fancy statistical tricks).

The most basic concept of clinical trials is statistical significance – is there an effect or correlation that is probably greater than chance. Most studies rely upon the P-value, which is a measure of the chance the result occurring if the the null hypothesis (no effect) is correct. A P-value of 0.05 means (roughly) that 5% (or 1 in 20) probability that the outcome is due to chance alone, and not a real effect. P-value of 0.05 is commonly used as a cutoff of statistical significance, but it is important to realize with this cutoff 1 in 20 studies of worthless treatments will appear positive due to chance alone. Lower P-values, such as 0.01, are more significant.

But P-value isn’t everything.  A poorly designed study can result in an impressive P-value. Also, the size of the effect must be considered. You can have a low P-value for a tiny effect (if there are large numbers of subjects in the trial) – the effect may be clinically insignifcant, and small effects are more likely to be due to hidden biases or confounders.

Therefore, we generally are only impressed when a clinically large effect also has a low P-value.

In addition to P-value, the number of subjects in the trial is very important. Even though these are related, the larger the study the more impressive the results, as random fluctuations are less likely to play a role.

One common trick to look out for is multiple analysis.  A study may, for example, look at 10 variables (or one variable at 10 different points in time), and find statistical significance for one, and present that as a positive study. However, this is equivalent to taking 10 chances at that 1 in 20 chance of hitting significance. Proper statistical analysis will account for multiple comparisons.

Other factors to look out for

There are features that are important to consider is evaluating a clinical trial. What was the dropout rate? If half of the subjects dropped out, that unrandomizes or biases the groups, because drop outs are not random. For example, subjects that do not respond to treatment may drop out, leaving only those who do well.

Not all controls are equal as well. Sometime the control group is not an inactive placebo but standard care. What if the standard treatment is too effective, or what if it is not effective at all. You need to know what the study treatment is being compared to.

Conclusion

When a new clinical trial is being promoted in the news as evidence for or against a treatment – run down this list. Is it a randomized, controlled, double-blind trial, is the blinding adequate, are the outcome measures objective and relevant, is the effect size robust, how large is the study, what variables are actually being isolated, and what was the drop out rate?

And of course, no one study is ever the definitive last word on a clinical question. Each study must be put in the context of the full scientific literature, which means considering plausibility or prior probability. That is the essence of science-based medicine.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a somewhat nebulous diagnosis with unknown etiology and no effective treatment. To make the diagnosis, bacterial infection must be excluded and the symptoms must last at least 3 months. Symptoms include pain in various locations (between rectum and testicle, in the testicles, at the tip of the penis, in the lower back, in the abdomen over the pubic or bladder area), pain or burning with urination, frequent urination, pain or discomfort during or after sexual climax. There are also systemic features like decreased libido, myalgias, and fatigue, and there is a higher incidence of chronic fatigue syndrome in these patients. The connection to the prostate is uncertain; in one study, women with chronic pelvic pain reported more of these symptoms than men did. Diagnosis is based on self-reported symptoms; there are no objective diagnostic markers. Somewhere between 2 and 10% of the male population are reported to suffer from this syndrome.

Since there is no effective mainstream treatment for this disorder, why not try acupuncture? Two randomized, placebo-controlled studies have reported positive results from acupuncture treatment. Is this enough evidence for us to recommend it to patients?

The Malaysian Study

This well-designed study was done in Malaysia, in a hospital with traditionally trained acupuncturists on its staff, in conjunction with the University of Washington Department of Urological Surgery. It was funded by the NIH and published in the American Journal of Medicine. There were 90 subjects randomized into two groups. They compared acupuncture at traditional points to sham acupuncture with more superficial needling 15 mm to the left of traditional points. They used no adjunctive treatments. They minimized interaction between participants and acupuncturists. They looked for a primary endpoint of a 6 point decrease from baseline to week 10 in a validated scale of symptoms, the NIH Chronic Prostatitis Symptom Index (NIH-CPSI), and for secondary outcomes including complete resolution and decreased scores at other intervals. They treated twice weekly for 30 minutes for 10 weeks, then followed the patients for an additional 24 weeks. They tested blinding by asking participants which therapy they thought they had received: 95% of those receiving acupuncture and 82% of those receiving the sham treatment thought they had received acupuncture. They found that acupuncture was twice as effective as sham acupuncture for the primary endpoint (73% vs. 48%, p=0.02) at 10 weeks, that more acupuncture patients had complete resolution of symptoms (18 vs. 10, p=0.07), and that acupuncture recipients had a greater long-term response 20 weeks after completing therapy (32% vs. 13%, p=0.04).

The Korean Study

The other study was done in Korea and was published in the journal Urology. It was a three-arm study comparing advice and exercise (A & E) alone to A&E plus electroacupuncture (where the acupuncture needles were electrically stimulated) to A&E plus sham acupuncture. There were only 13 men in each group. The sham acupuncture involved (1) more superficial needling, (2) placement 15 mm to the left of acupuncture points, and (3) the sound of the pulse generator without actual electrical stimulation. In the acupuncture group they found a significant reduction in the NIH-CPSI scores for pain, but no reduction in the scores for urinary symptoms or quality of life. On another scale, the International Prostate Symptoms Score, there were no significant differences. There is no mention of an exit poll to see if patients could guess which treatment they had received.

This study had one other intriguing wrinkle. There had been some hints of a correlation between prostatitis symptoms and prostaglandin E and beta endorphin levels, so they measured these in post-massage urine samples. They found a significant decrease in prostaglandin level in the electroacupuncture group (p=0.023) and a non-significant increase in the other two groups. They present a bar graph that makes it look like the increase in the sham group was more significant than the decrease in the electroacupuncture group, but they don’t provide the raw data or even report calculated p values, so we can only guess what the bars mean.

There was no significant change in endorphins for any group. It’s intriguing that they were able to measure something objective, but at this point, without replication, it’s impossible to say what the data mean, if anything.

Other Studies

A PubMed search for “clinical trials, chronic prostatitis and acupuncture” brought up these two studies and only 5 others that were a mish-mash of different kinds of prostatitis and different treatments: warm needle moxibustion, suspended moxibustion (where a burning stick is held above the acupuncture point with no skin contact), abdominal cluster needling, sometimes in association with herbal enemas and other treatments. A meta-analysis of case-control studies out of China found a significantly higher cure rate with acupuncture than with controls, but they were looking at studies of a different diagnosis: chronic prostatitis, not chronic prostatitis/chronic pelvic pain syndrome. And none of the studies were randomized controlled trials.

Additionally, the Korean study referenced another study that did not come up on my PubMed search for some reason. This study of CP/CPPS involved three sets of acupuncture points totaling 30 points (8 points were electrically stimulated) given alternatively twice weekly for 6 weeks. It showed an even more impressive effect: 83% of subjects reported marked improvement, but it was an uncontrolled pilot study with only 12 subjects.

So we don’t have a lot of evidence, but the evidence we do have consistently supports acupuncture for CP/CPPS. Acupuncturists can say their treatments are evidence-based.

Discussion

As you may have guessed, I have some reservations. In the first place, what do they mean by acupuncture? The Malaysian study used 4 acupuncture points: CV1, CV4, SP6 and SP9. The Korean study used acupuncture points BL 32, Bl33, GB30 bilaterally, for a total of 6 entirely different points. The Malaysian study used only needle insertion; the Korean study used electrical stimulation. The pilot study used 30 points with electrical stimulation of 8 of them. If you were going to do acupuncture based on these studies, which points would you choose?

Studies can’t really support each other if they’re not testing the same treatment, can they? In addition, even the Malaysian study was not a test of acupuncture per se. The “true” acupuncture arm did not even attempt to elicit the “de qi” sensation that many acupuncturists consider essential to the acupuncture effect. They followed a rigid protocol rather than offering the kind of individual treatment adjustments acupuncturists typically use in practice. And they did not twirl or stimulate the needles in any way after insertion. If their results had been negative, they might well have argued that their study didn’t discredit acupuncture because it didn’t represent the practice of acupuncture at all.

More importantly, we need to look at these studies in the context of everything else we know. Good studies with better controls (retracting needles) have shown no difference between acupuncture points and non-points. Other studies with toothpicks and with simple electrical transcutaneous stimulation have shown that it doesn’t matter whether the skin is penetrated. So many studies have shown sham acupuncture to be equal to “true” acupuncture that in several recent studies acupuncturists themselves have chosen not to use a sham acupuncture control on the theory that it is not a placebo control because any skin stimulation is effective. (But then what is acupuncture??!!) And even the best studies are not double blind: double blind studies would be extremely difficult to design, since the acupuncturist is aware of what he is doing.

Another concern is that studies from Asian countries are prone to the “file drawer effect” where negative studies are filed away rather than submitted for publication. This is a bigger problem in Asia than elsewhere: 98% of published acupuncture trials from Asia are positive, versus 30% of acupuncture trials from Canada, Australia and New Zealand. What if most of the evidence is really negative? What if 4 studies were done, 3 with negative results and one with positive results, and only the one with positive results was submitted for publication? Replication in a country with a better track record would make the results more credible.

We know there are many things that can go wrong with experiments, and that most published research findings are false. When initial findings are mixed for a treatment that really works, there is a gradual accumulation of more convincing data that tips the balance over time. Acupuncture studies have never shown any such progress.

I will admit to being prejudiced by the fact that acupuncture is based on pre-scientific thinking and on points, meridians and vitalistic forces whose existence can’t be demonstrated. But we wouldn’t have to know “how” it worked if it clearly “did” work. The evidence is inconsistent and not robust enough to convince rigorous scientists that acupuncture is more effective than placebo for any medical condition.

A Question Rather Than a Conclusion

Since medical science has little to offer for CP/CPPS, is recommending acupuncture ethically justified; and if so, should patients be told it is evidence-based?

A common theme in alternative medicine is the “One True Cause of All Disease”. Aside from the pitiable naivete, it’s implausible that “acidic diet”, liver flukes, colonic debris, the Lyme spirochete, or any other problem—real or imagined—can cause “all disease” (in addition to the fact that most of these ideas are intrinsically mutually exclusive).

One of the popular new ideas in this category is that of “endocrine disrupting chemicals” (EDCs). These are chemicals in the environment that physiologically or chemically mimic naturally occurring human hormones. That some environmental substances are chemically similar to human hormones is indisputable. That these substances can have a real physiologic effect in vitro seems to hold up. How much of an effect these chemicals may have in real human populations is an open question.

And unlike many similar ideas, there are a lot of plausible questions that are under investigation. And this is where I fear our colleagues in the media lose it. The media can be an effective source of public health information, even a tool to improve public health, but when the media unleashes a torrent of premature speculation, science and the public health lose. This is where the Times’s Nicholas Kristoff comes in. On Sunday, he asked these questions:

The battle over health care focuses on access to insurance, or tempests like the one that erupted over new mammogram guidelines.

But what about broader public health challenges? What if breast cancer in the United States has less to do with insurance or mammograms and more to do with contaminants in our water or air — or in certain plastic containers in our kitchens? What if the surge in asthma and childhood leukemia reflect, in part, the poisons we impose upon ourselves?

We have many examples of human-made environmental chemicals causing disease.  Often, a cluster of disease is identified, and then a common exposure is found, and further study confirms a likely causal relationship.  For example, in the 20th century, thousands of people in Minamata, Japan fell ill and died from a mysterious neurological ailment.   Investigation found that industrial methyl mercury contamination had entered the seafood chain  and was the responsible agent.

Conversely, suspect contaminated regions can be identified, and then clusters of disease can be sought.  This is a bit trickier, but still a legitimate way of investigating a relationship.  The Michigan PBB incident in one such example in which health effects were hard to nail down.  Cigarette smoking as a cause of cancer was a bit more clear.

A less effective way to approach this type of problem is to have neither a clear disease cluster nor a clear exposure group.  This is the mistake made by Kristoff.  He relates EDCs to several problems, but focuses on breast cancer, drawing a line from EDCs to early puberty, to longer time from menarche to menopause, to increased breast cancer rates.  While this is not implausible, it’s pretty damned tenuous.  In order to see if EDCs are really causing breast cancer in significant numbers, we should establish both a correlation between exposure to specific chemicals and excess cases of breast cancer. We should also have a laboratory model for the connection.

The problem here from a science-based medicine perspective is not the implausibility but the oversimplification and naive, hyperbolic conclusions.  Kristoff cites a 56-page report from the Endocrine Society, which was much more circumspect and called for further study of the issue.  I can understand the desire to communicate an important health story to the public, but choosing an emotionally charged issue like breast cancer and linking it to everyday substances that everyone uses blurs the issue more than it clarifies.  It incites emotion without asking clear, important questions.

When I’ve talked to experienced public health experts about EDCs, they’ve given me a noncommittal, “yeah, there could be something to that,” but none that I’ve read have been willing to call this a major public health threat.  We know the causes of lots of cancers.  We know how to screen for many important cancers, which allows for early detection and treatment.  Some cancers we can actually prevent by limiting environmental exposures;  many lung cancers could be prevented by eliminating exposure to cigarette smoke.   Whether any cancers can be prevented by banning putative EDCs is a question that’s barely been asked, much less answered.

Lose weight without diet or exercise? I guess that leaves cancer.

It is the day after Thanksgiving, and I have probably eaten enough calories to support the average family for at least three days. I am hesitant to comment on what my actual weight may be, but others have not been so reticent about discussing my appearance over at RDCT. At least I am not female; then I would get no end of critiques based on my looks.

Now that I am up a few holiday pounds, it would be nice to lose some weight. Of course I do not want to do it the old fashioned way, with diet and exercise. Diet and exercise take time and are fundamentally painful. I want to eat what I want when I want from the comfort of my Lazy Boy. I want an easy way to lose weight. The interwebs, as is often the case, have been kind enough to provide me with numerous emails suggesting all sorts of simple ways to alter my physique for the better, some of which even include weight loss.

For some reason I have been on a spam list that keeps me well supplied with offers to try acai berry juice to lose weight.

Acai is a palm tree whose fruit, like that of many palms, is a food source for the indigenous peoples in the area where they grow. The akai berry is grape sized and purple and if it is purple it must be good. Of late acai has been touted for a wide number of health benefits, including weight loss, because it is believed to be high in antioxidants.

How do antioxidants help you lose weight?

According to the weight loss center antioxidants can help with weight loss as follows

“The reality is that antioxidants may very well improve weight loss or, at the very least help provide the body with the nutritional support it needs to keep it strong and energized during the fat burning process.

To help you understand how antioxidants can enhance weight loss, you need to take a closer look at the actual process that occurs when we lose fat. While most people tend to look at fat as their enemy when they are overweight, it is imperative that you realize fat is necessary for our health. There are two types of fat:

1. Essential fat – necessary for many body functions including reproduction.
2. Storage fat – Essential for protecting some of the body’s organs.

The fat in our bodies is stored in our adipose tissue. This tissue contains lipids that are needed to transform nutrients into energy. Fat cells have many functions and one of them is to store toxins that are released throughout the digestive process. Thus, when you reduce the fat in your body, the amount of toxins in your body increases and this can result in some negative side effects. For instance, the extra toxins often affect the liver, causing it to work overtime to process and remove them. Moreover, when fat molecules are broken down, a process called oxidation, they release free radicals, which can result in cell, protein and DNA damage.

Oxidation occurs when free radicals (unstable atoms) attack cells to re-stabilize themselves. The re-stabilized atoms release more free radicals and the process continues like a chain reaction throughout the body until the free radicals are stopped. The body will create its own antioxidants to help stop the reaction, but often there is not enough, which is why ingesting foods or supplements rich in antioxidants can be beneficial.

Thus, when you lose weight, you are not only shedding excess fat, you are also losing some of the nutrients in your body that are needed to maintain good health. Also, if you are exercising as part of your healthy weight loss program then your body will be creating even higher levels of toxic by-products. Therefore, antioxidants can help provide your body with the nutritional support it requires during the oxidation process, reducing the stress on your body and keeping energy levels and metabolism as high as possible.”

Huh? So as best as I can tell from this tortuous explanation, antioxidants contribute to weight loss by nutritional support. It appears the the purpose of antioxidants is not so much to help stimulate weight loss but to act like a catalytic converter, taking off the ‘toxins’ generated by fat oxidation. Just where these anti-oxidized toxins then go is never mentioned. This is one of the more coherent explanations I have found. My rule of thumb is that if a product provides support and is not an undergarment, it is crock.

Is there data to support the use of any antioxidants to help with weight loss? Not that I can find. Although there are many interweb claims that antioxidants help with weight loss, Pubmed and Google Scholar are silent on the topic. So despite the common use of supplements as an adjunct to weight loss, there is nothing to support the use of antioxidants, in acai or other foods, in weight loss.

Ironically, there is at least one study to show that antioxidants may help with weight gain in AIDS and cancer, although I doubt the increase in weight was due to any antioxidant properties of the supplements. Antioxidants may also prevent some of the beneficial effects of exercise as well. The take home message, as is often the case in medicine, is that the effects of supplements on physiology are rarely simple or straightforward.

So antioxidants have no role in weight loss outside of an advertising gimmick.

Back to acai. From Google trends, acai juice seems to be a relatively new fad in the US. Searches for the product stated in volume in the middle of July, 2008. While association is not causation, it is worth noting that the big spike in Google searches occurred shortly after Dr. Oz mentioned acai on Oprah

The Oprah mention apparently spawned the acai industry with the inadvertent help of Dr. Oz and Oprah, who are now suing the acai companies for using their likenesses and for implying that Oz and Oprah were supporting acai and using their good name. Do not mess with Oprah and suggest she gives your product a seal of approval.

The other industry spawned at the time was the acai scam, where people will sign up for ‘free’ acai using their credit card for shipping and handling, and then get charged large sums and be unable to cancel the order. Do NOT order acai online. If you are going to purchase worthless products, buy them at your local supplement store.

Like silver or other supplements, there is also a growth industry in the real acai, as opposed to all the posers who are peddling second rate products. One of the more important features of quality acai is the ORAC levels. Really. Orac. Go figure. But I do prefer high levels of Orac. The most amusing part of the acai industry is that the model used in many of the websites for ‘before’ and ‘after’ is a photo-shopped iStockphoto who never used the product. I wonder if the second rate acai products leads to photo-shopped weight loss.

“There are no magical berries from the Brazilian rainforest that cure obesity—only painfully real credit card charges and empty weight loss promises,” said Connecticut Attorney General Richard Blumenthal. “Aggressive Acai berry pitches on the Internet entice countless consumers into free trials promising weight loss, energy and detoxification. These claims are based on folklore, traditional remedies and outright fabrications—unproven by real scientific evidence. In reality, consumers lose more money than weight after free trials transition into inescapable charges. We will investigate these allegedly misleading or deceptive nutrition and health claims and take action under our consumer protection statutes—as we have done with other food products.”

This is the same Blumental who sued the Infectious Disease Society of America for anti-trust for their Lyme treatment guidelines, so I doubt it is a deep understanding of science and medicine that guides his actions.

So is there anything at all to acai as a way to lose weight? Perhaps.

Eating the fruit straight from the tree may give you Chaga’s, a parasite that destroys your heart and esophagus, rendering you unable to eat, so you might lose weight that way. Hardly seems worth it. Analysis of the fruit does show it has vitamin C and a variety of antioxidants, so it is not bad for you. But there are more palatable alternatives:

“ PJ (pomegranate juice) had the greatest antioxidant potency composite index among the beverages tested and was at least 20% greater than any of the other beverages tested. Antioxidant potency, ability to inhibit LDL oxidation, and total polyphenol content were consistent in classifying the antioxidant capacity of the polyphenol-rich beverages in the following order: PJ>red wine>Concord grape juice>blueberry juice>black cherry juice, açaí juice, cranberry juice>orange juice, iced tea beverages, apple juice. Although in vitro antioxidant potency does not prove in vivo biological activity, there is also consistent clinical evidence of antioxidant potency for the most potent beverages including both PJ and red wine.”

Is there anything special from acai? I am uncertain and unenthusiastic. It is safe to say, if you have ever had a Bordeaux, that the Connecticut Attorney General was only partly wrong, that magic berries can be found in France. There is nothing special about acai except the hype.

If you are not interested in spending money on acai juice, I found a more direct way to rid your self of 10 pounds of ugly, unwanted fat. Rather than have the fat go away from metabolism, inject it away. Maybe I can be rid of the turkey and gravy with mesotherapy. What is mesotherapy? It is

“ a minimally invasive technique that consists of the intra- or subcutaneous injection of variable mixtures of natural plant extracts, homeopathic agents, pharmaceuticals, vitamins, and other bioactive substances in microscopic quantities through dermal multipunctures.”

Minimally invasive is correct, as the needles used in mesotherapy are 3 mm long.

Mesotherapy has a curious origin, oddly familiar to those who wander the fringes of medicine.

In 1952 a French physician, Michel Pistor, treated a man with asthma with IV procaine, an anesthetic, and while it did not help the patients asthma, it did improve the patients hearing, DD Palmer be praised. Dr Pistor at that point decided to inject the procaine superficially around the ear, and while it did not restore hearing in other patients, others had improvement in their temporal-mandibular joint pain syndrome, eczema, and tinnitus.

Of course, this therapy was a panacea, not limited to treating hearing loss, but used for treating systemic problems with local superficial injections. Dr Pistor said ‘‘the action on tissue originating from the mesoderm is so extensive that these treatments deserve the global name of mesotherapy’’ and a new branch of medicine, at least in France, was launched.

The list of diseases treated with mesotherapy is extensive:

‘Allergies, arthritis, asthma, carpal, tunnel, syndrome, cellulitis, chronic, fatigue, constipation, degenerative, disc, disease, depression, fibromyalgia, gout, headache, hearing, loss, hemorrhoids, hepatitis, herpetic, neuralgia, immune, system, deficiencies, insomnia, irritable, bowel, syndrome, lower, back, pain, lymphedema, obesity, osteophytes, (‘‘bone, spurs’’), peripheral, vascular, disease, prostatitis, reflex sympathetic, dystrophy, sports injuries, (i.e.,, sprains,, strains, tears,, bursitis,, tendonitis, plantar, fasciitis, calcium, deposits), substance, abuse, temporal-mandibular, pain, syndrome, tinnitus, and vertigo.”

A large numner of diseases require a remarkable number of substances to be injected with mesotherapy, not limited to

“ T3-T4 thyroid, isoproterenol, aminophylline, pentoxifylline, l-carnitine, l-arginine, hyaluronidase, collagenase, yohimbine, lymphomyosot, co-enzyme cofactors, dimethylethanolamine, gerovital, glutathione, tretinoin, alpha lipoic acid, vitamin c, procaine, lidocaine, ginkgo biloba, melilotus, c-adenosine monophosphate, multiple vitamins, phosphatidylcholine, trace mineral elements, and carbon dioxide” and more as well as homeopathic preparations.

Mesotherapists choose their injectables for their alleged effects, for example injecting an NSAID for anti-inflammatory effects or artichoke (really) for circulatory stimulation. Often multiple substances are mixed together, based on the experience of the mesotherapist, rather than data, into a cocktail that is then injected.

There are less than a dozen articles in the European medical literature to support the use of mesotherapy for medical conditions such as pain and musculoskeletal conditions and have the same rigor as acupuncture studies.

In the US mesotherapy is used primarily for cosmetic changes and body sculpting, but also to ‘dissolve fat’ and treat cellulite. Its efficacy is debated as evidenced by one review entitled “Cosmetic mesotherapy: between scientific evidence, science fiction, and lucrative business.”

The plastic surgery literature often states that mesotherapy is not the same as using injections of phosphatidylcholine and deoxycholate to remove superficial fat, for which there is some supporting literature. Histopathology after phosphatidylcholine and deoxycholate injections demonstratess an inflammatory response with fat necrosis, and there may also be some fat necrosis from traditional mesotherapy products as well .

Part of determining if mesotherapy can lyse fat is defining what constitutes mesotherapy, what kind of fat you are trying to eradicate and, with what are you injecting. One patient, with congenital large symmetrical fat collections was treated with good cosmetic effect with injections of phosphatidylcholine, but many would not consider this mesotherapy since the phosphatidylcholine was injected deep into the fat.

Whether similar or other injections are beneficial for cellulite or other superficial fat depositions cannot be determined; the data to date is minimal and suggests it is without efficacy. Unfortunately mesotherapy is worthless for the turkey induced muffin top. It can run thousands of dollars and, to judge from sites not promoting mesotherapy, it is both painful and useless. Many who use ‘CAM’ seem to like to ‘do it yourself’, but I would advise against home mesotherapy with lipase .

Mesotherapy is not FDA approved, but since the products are (except, I suppose, for artichoke) FDA approved medications, they can be used off label by mesotherapists.

While efficacy is uncertain and cost is variable, what is well described are the complications. There are numerous outbreak reports of infections with atypical mycobacteria, cousins of Tb, that cause long term scarring. Not unsurprisingly, some of the outbreaks are due, in part, to the practitioner not using standard sterile technique.

“Fourteen patients reported breaches in safe-injection practices by the practitioner, including 1) failure to practice hand hygiene, 2) failure to prepare the skin with an antiseptic, 3) failure to wipe vials with alcohol before injection, and 4) failure to wear gloves. Of 11 patients who could recall, all reported use of a new needle; however, nine patients reported use of a multidose vial. Patients reported being told their injections contained various substances (e.g., plant extracts from artichoke and thuja, liquid “graphites,” and procaine). With the exception of procaine, none of the substances reported by patients have been approved for subcutaneous injection by the FDA. ”

Mesotherapy is also associated with care reports of other odd reactions including thyrotoxicosis, septic arthritis, and a variety of local skin reactions. I wonder if I were to get a mesotherapy injection with acai juice…

I suppose I am still stuck with diet and exercise.

Go Ducks.

Its authors boast that it is one of the ten most downloaded papers from the British Medical Journal (BMJ). That makes it even more unfortunate that the conclusions of the paper are directly at odds with the findings of the paper. Outcomes of planned home births with certified professional midwives: large prospective study in North America by Kenneth Johnson and Bettye Ann Davis is the premier paper on the safety of American homebirth. It claims to show that homebirth is as safe as hospital birth, but actually shows that homebirth has nearly triple the neonatal death rate of hospital birth for comparable risk women.

Johnson and Daviss, in collaboration with the Midwives Alliance of North America (MANA), the organization of American homebirth midwives, collected data on all homebirths attended by Certified Professional Midwives (CPMs, homebirth midwives, as distinct from CNMs, Certified Nurse Midwives) in the year 2000. Then the authors compared the outcomes for interventions and for neonatal deaths with a hospital group.

According to Johnson and Davis, when analyzing the different intervention rates of home and hospital:

We compared medical intervention rates for the planned home births with data from birth certificates for all 3 360 868 singleton, vertex births at 37 weeks or more gestation in the United States in 2000, as reported by the National Center for Health Statistics [Births: final data for 2000. National vital statistics reports. Martin JA, Hamilton BE, Ventura SJ, Menacker F, Park MM. Hyattsville, MD: National Center for Health Statistics, 2002;50(5)]

They used singleton, vertex births at 37+ weeks as a proxy for low risk women. They found, not surprisingly, that intervention rates are lower for homebirth. Then they turned to neonatal mortality rates. They should have compared the neonatal mortality rate of the homebirth group to the neonatal mortality rate of the hospital birth group, but they did not. Instead, they compared homebirth deaths to hospital births in a variety of out of date studies extending back more than 20 years.

The authors conclude:

Planned home birth for low risk women in North America using certified professional midwives was associated with lower rates of medical intervention but similar intrapartum and neonatal mortality to that of low risk hospital births in the United States.

But the authors never compared mortality rates to low risk hospital birth in 2000, because that would have led to a very different conclusion. Using the same dataset that Johnson and Daviss used, we find hospital neonatal death rate for white,  babies at 37+ weeks of 0.9/1000. This is not corrected for congenital anomalies, pre-existing medical conditions, pregnancy complications or multiple births. The neonatal mortality rate for white, singleton babies at 37+ weeks is 0,72/1000. The true rate is substantially lower. Nonetheless, we can make an important comparison. Johnson and Daviss reported a neonatal death rate at homebirth of 2.7/1000 (uncorrected for congenital anomalies, breech or twins). In other words, the neonatal death rate of CPM attended homebirths in 2000 was nearly triple the rate for low to moderate risk hospital births in 2000.

Simply put, the authors pulled a bait and switch. They claim to be comparing homebirth in 2000 with hospital birth in 2000. Indeed, they are comparing intervention rates for homebirth in 2000 with hospital birth in 2000, but when it comes to neonatal deaths, they used data extending back to 1969. It was the only way to make homebirth look safe by comparison.

Why might the authors deliberately intend to deceive readers? It turns out that Johnson and Daviss are not impartial researchers, though you would not know that from reading the paper. Johnson is the former Director of Research for the Midwives Alliance of North America (MANA) Statistics and Research Committee. Daviss, his wife, is a homebirth midwife. The paper does acknowledge that the study was funded by Foundation for the Advancement of Midwifery, a homebirth advocacy group.

Johnson and Daviss have created a website, Understanding Birth Better, to answer criticism. However, their explanation for the bait and switch is not merely disingenuous, it is an outright lie.

… Since our article was submitted for publication in 2004, the NIH has published analysis more closely comparable than was available at that time, and some have tried to use it as a comparison. While we still do not offer the comparison as a completely direct one, … it is the closest we have …

As they say in politics, it’s not the crime, but the cover up. Johnson and Daviss acknowledge that they used the wrong group for comparison with homebirth, but claiming that the correct data was not available at that time. That is flat out false.The relevant data was published in 2002, long before their paper was submitted (Infant Mortality Statistics from the 2000 Period Linked Birth/Infant Death Data Set, published August 29, 2002). Moreover, even before publication of the analysis, Johnson and Daviss had the raw data in their possession. They used that raw data from 2000 to calculate the rates of hospital interventions, so they were fully aware of the mortality data at all times.

It is difficult to imagine a legitimate reason why a professional statistician would deliberately use the wrong statistics for comparison when the right statistics were available and actually in his possession. It seems to me that the only possible explanation is that they knew all along that their study showed that homebirth has an increased risk of preventable neonatal death compared to hospital birth.

Regardless of reasoning or excuses, the bottom line is stark: rather than showing that homebirth with an American homebirth midwife is safe, the Johnson and Daviss study actually showed that homebirth with a CPM in 2000 had nearly triple the neonatal death rate of moderate to low risk hospital birth in 2000.

While doctor visits for influenza-like illnesses seem to be trending downward again, and ”swine flu” is becoming old news, I’d like to draw attention to an H1N1 story that has received very little coverage by the mainstream media.

Doctors in several states can now protect their most vulnerable patients from the H1N1 virus without worrying about breaking the law. In order to save lives, several states have announced emergency waivers of their own inane public health laws, which ban the use of thimerosal-containing vaccines for pregnant women and young children.

Legislators in California, New York, Illinois, Missouri, Iowa, Delaware, and Washington state have enacted these science-ignoring laws in response to pressures from the anti-vaccine lobby and fear-struck constituents. Except for minor differences, each state’s law is essentially the same, so I will focus on the one from my state of New York.

New York State Public Health Law §2112 became effective on July 1, 2008. It prohibits the administration of vaccines containing more than trace amounts of thimerosal to woman who know they are pregnant, and to children under the age of 3. The term “trace amounts” is defined by this law as 0.625 micrograms of mercury per 0.25 mL dose of influenza vaccine for children under 3, or 0.5 micrograms per 0.5 mL dose of all other vaccines for children under 3 and pregnant women. Because thimerosal (and thus, mercury) exists only in multi-dose vials of the influenza vaccines (both seasonal and novel H1N1), this law really only applies to these vaccines. The mercury concentration of the influenza vaccines is 25 micrograms per 0.5 mL, which therefore makes their use illegal. Unfortunately, the only form of the H1N1 vaccine initially distributed, and that could be used for young children and pregnant women, was the thimerosal-containing form. The thimerosal-free vaccine was the last to ship, and in low supply, and the nasal spray is a live-virus vaccine, not approved for use in pregnancy or children under 2. That meant, without a waiver of the thimerosal ban, these groups could not be vaccinated.

There is no scientific evidence that thimerosal in vaccines poses any risk to children,  pregnant women, or their fetuses. In fact, the evidence contradicts the claims by the anti-vaccine lobby that thimerosal in vaccines is a cause of autism. On a multitude of levels there is ample reason to reject any link between thimerosal and autism:

1. All of the legitimate studies to date have failed to demonstrate any link.

• Thimerosal-Containing Vaccines and Autistic Spectrum Disorder: A Critical Review of Published Original Data
• Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
• Thimerosal Exposure in Infants and Developmental Disorders: A Prospective Cohort Study in the United Kingdom Does Not Support a Causal Association
• Safety of Thimerosal Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Databases

2. The apparent increase in autism cases has continued even after the removal of thimerosal from vaccines.

• Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population-Based Data
• Continuing Increases in Autism Reported to California’s Developmental Services System: Mercury in Retrograde
• Pervasive Developmental Disorders is Montreal, Quebec, Canada: Prevalence and Links with Immunizations

3. Finally, and a usually neglected part of the story, the kind of mercury contained in thimerosal (ethylmercury) is very different from the kind produced by industrial pollution, and that ends up in the fish you eat (methylmercury). While methylmercury becomes concentrated in the body’s tissues (most importantly the brain) and thus remains for prolonged periods, ethylmercury is much more rapidly eliminated, and is therefore much less readily stored by the body. Recent studies have demonstrated just how different the pharmacokinetic properties of these two types of mercury are in the bodies of infants. This is important when we consider the US EPA “reference dose” (RfD) for mercury. This is the upper level daily amount, over a lifetime, of a substance that is considered safe to the most sensitive individuals in a population. The RfD for mercury set by the EPA is 0.1 micrograms per kilogram of body weight per day. Many people who believe the thimerosal-autism link point to the fact that, before thimerosal was removed from vaccines, some infants received a total daily dose of mercury from vaccines that came close to or exceeded the EPA’s RfD for mercury. Keep in mind, however, that the RfD was based on long-term, life-time daily exposures, not one time or even multiple time exposures. Also, as a safety factor the RfD was set 10 times higher than the actual estimated safe level. But most importantly, the RfD for mercury is based on data for methylmercury, not ethylmercury. That is, all the assumptions about the hypothetical dangers of exceeding the RfD for mercury, on potentially a few occasions, are based on an RfD for the wrong kind of mercury. As discussed above, the data on the pharmacokinetics of ethylmercury suggests a very different, and far less concerning picture for thimerosal in vaccines.

But let’s return to the legislation at hand. Besides their inclusion under this thimerosal ban, what else is exceptional about pregnant women and children under the age of 3? Well, they happen to be at greatest risk for serious complications of H1N1 disease, and are considered to be the highest priority populations for receipt of the vaccine. So, ironically, those at greatest risk for severe morbidity and mortality from the disease, and who are at the top of the list for getting the vaccine, aren’t permitted by law to receive it. Until, that is, states began issuing emergency waivers of these absurd laws.

To be fair, written into the law is a provision for the Comissioner of Public Health to waive the law during times of vaccine shortage or in the event of a severe outbreak. The important point, however, is what the very existence of these laws reveals about the power of the anti-vaccine lobby and a fear-stoked constituency. The fact that 7 states have enacted laws banning thimerosal-containing vaccines, and that there is similar legislative activity occuring in several other states, is a testament to the power of fear over reason, and the struggle of science to gain a foothold in our national consciousness. Although California has also temporarily waived their thimerosal ban, California’s secretary of Health and Human Services, Kim Belshe, issued this dark-aged rejoinder,

We take very seriously the expressed concerns that mercury in vaccines causes autism and remain committed to full implementation of [the law]

One of the greatest dangers of this trend away from a scientific view of medicine, and toward a more individualistic or even democratic one, is the solidification of this group think into the bedrock of legislation. The legislative process, shaped by constituencies, lobbies, and the personal leanings and beliefs of legislators, is frighteningly susceptible to irrational and anti-scientific forces. Glaring examples of this can be seen in the enactment of the Dietary Supplement Health and Education Act of 1994, the formation of the National Center for Complementary and Alternative Medicine in 1998, the establishment of Title V, Section 510 of the Personal Responsibility and Work Opportunity Reconcilitation Act (A.K.A. abstinence only education) in 1996, and the numerous insurance equality laws most states have enacted to mandate insurance coverage of chiropractic treatemnts, and other so-called “CAM” providers. This last type of legislation is particularly concerning. The newly formed Institute for Science in Medicine is currently working to address stealth provisions in health care reform legislation, now being debated in the Senate, that seek to legitimize “CAM” practitioners and mandate insurance coverage for a wide array of medically invalidated treatments. If this legislation is passed, more anti-science will be foisted upon our nation’s system of health care.

A quote from the recent New York Times review of Michael Specter’s new book, “Denialism“, sums up this trend toward “giving the people what they want” in health care. Although democracy is a wonderful way to run a nation, it isn’t how we develop science-based medicine.

…for better or worse, people are more skeptical of authority than they used to be and want to think for themselves, which includes grappling with the minutiae of science. Not so long ago, for example, patients rarely questioned doctors before undergoing surgery or taking their pills (for example, estrogen replacement therapy to prevent heart attacks), a blind obedience to authority that arguably cost many more lives than, say, vaccine refusal does now. What we are seeing is the democratization of science…

Many parents of children with autism have expressed to me their dismay that the anti-vaccine lobby is sucking all the oxygen out of the room for autism awareness. They feel that just being a parent of a child with autism makes others assume that they are anti-vaccine. They also worry that resources and attention are being diverted from promising legitimate research because of all the attention being paid to the failed vaccine hypothesis.

So it is good to occasionally focus on mainstream autism research to show that progress is being made, despite the unfortunate anti-vaccine sideshow.

A recent study published in the latest issue of Pediatrics shows that early intervention in toddlers with autism can have significant benefits. The study is a randomized controlled trial of  the Early Start Denver Model compared to conventional treatment in 18-30 month old children with a diagnosis of autism spectrum disorder (ASD). The study is a reasonable size for this kind of intervention – 48 children were randomized – and this is sufficiently powered to get statistical significance. But it should be noted this is still a smallish study and replication to confirm the results is welcome.

Another potential weakness is that the control group was “referral to community providers for intervention commonly available in the community.” Therefore the control group was not standardized and it’s possible this group was sub-optimally treated. Further, while the groups were randomized they were not blinded.

The results of the study are quite robust:

Compared with children who received community-intervention, children who received ESDM showed significant improvements in IQ, adaptive behavior, and autism diagnosis. Two years after entering intervention, the ESDM group on average improved 17.6 standard score points (1 SD: 15 points) compared with 7.0 points in the comparison group relative to baseline scores. The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children. In contrast, over the 2-year span, the comparison group showed greater delays in adaptive behavior. Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder, not otherwise specified, than the comparison group.

The results of this study are plausible and encouraging, and hopefully will lead to further studies to confirm the results.

The concept behind ESDM is this (from the EarlyDevelopment Studies Lab website):

Autism impedes this process of child learning and adult scaffolding, in several ways.  Children with autism are less attentive to other people and so miss many learning opportunities by watching. Young children with autism have impaired communication skills, so they have difficulty learning from the communications that adults provide. Young children with autism also have difficulty imitating others, and so miss opportunities to learn by copying what others do. Young children with autism may not be quite as flexible in their play skills as others, and may enjoy repeating favorite actions with objects, rather than generating new play ideas and learning through discovery, and this limits their learning. And finally, young children with autism may not find social experiences as inherently rewarding as other children, which can result in reduced time in interactions of all sorts. Since interactions are a primary learning opportunity for toddlers, fewer interactions mean fewer learning opportunities.

The ESDM is designed to make learning for young ASD toddlers more fun, dynamic, and child-directed rather than repetitive. The purpose is to compensate for the specific areas of difficulty of ASD children.

While not a “cure” if these results hold up ESDM can be a very effective early intervention for children with ASD. It highlights the potential benefit of early detection and intervention programs.

It also brings to mind the broader context (which is relevant to many neurological diseases and disorders) that at times focus on finding a cure might overshadow research and even clinical attention paid to interventions that improve quality of life and mitigate the impact of a disorder. Finding a cure is, of course, always the long term goal. But we have to be realistic in recognizing that for many complex disorders it is a very long term goal. Meanwhile there is much that can be done to significantly improve outcome, and these types of interventions should not be neglected simply because they are not a “cure.”

Patients and families need to recognize that often there is much that can be done, and they should not neglect medical attention under the false belief that “nothing can be done” simply because a cure does not exist yet. Sometimes, even clinicians need to be reminded of this fact.

Also, research priorities should reflect a reasonable balance between searching for a cure and improving outcomes in the meantime. Grassroots advocacy groups that raise funds for clinical research, in my opinion, often over-emphasize research that has the potential to find a cure in the short term, and may in fact slow overall research progress by upsetting the balance between various kinds of research (basic, therapeutic, and symptomatic).

So it is good to see a solid symptomatic trial like this one get attention, and to remind people that we can make a significant difference with science-based interventions in the lives of children with ASD, even if we don’t fully understand the disorder or know how to cure it.

Nasal irrigation with salt water is recommended by 87% of family doctors as an adjunctive treatment to relieve the symptoms of nasal congestion and sinusitis. The simplest method is to hold salt water in your cupped hand, block one nostril while you inhale the water into the other nostril, then blow your nose. The high-tech version is to use a Neti pot, a little jug with a spout. You pour the salt solution from the Neti pot into one nostril and it drains out the other nostril. The technique is described here.  

The Neti pot originated in India in Ayurvedic medicine. Neti is Sanskrit for “nasal cleansing.” Other related ancient techniques that have not been adopted by scientific medicine include using a string instead of water and a yoga technique where you close one nostril, pour the solution into the other nostril and allow it to run out of the mouth. 

Nasal irrigation provides short-term symptomatic relief and may improve nasal mucociliary clearance. It removes mucus not only from the nose but also from the maxillary and ethmoid sinuses.  

A randomized controlled trial in 2002 found that daily hypertonic saline nasal irrigation improves sinus-related quality of life, decreases symptoms, and decreases medication use in patients with frequent sinusitis.  Its effectiveness is supported by a Cochrane review.  

A recent review article in American Family Physician  gave nasal irrigation an “A” strength of evidence rating as an effective adjunctive therapy for symptoms of chronic rhinosinusitis, and  a “B” rating for irritant and allergic rhinitis and viral upper respiratory infections. 

Just don’t overdo it. A new study presented at the annual meeting of the American College of Allergy, Asthma and Immunology in November 2009 found that while short-term nasal irrigation is therapeutic, long-term use of nasal irrigation is harmful. Regular users of irrigation who continued using it had an average of 8 episodes of recurrent rhinosinusitis per year, while those who discontinued it only averaged 3 episodes per year.  The investigators hypothesized that the nasal mucosa serves as the first line of defense, and irrigation depletes the nose of its immune blanket of mucus, thereby increasing the risk of recurrent infection.

I’ve been writing about the attempts of proponents of various pseudoscience, quackery, and faith-based religious “healing” modalities to slip provisions friendly to their interests into the health care reform bill that will be debated in the Senate beginning today. If you want to know what’s at stake, check out the first press release of a newly formed institute designed to promote science-based medicine in academia and public policy, the Institute for Science in Medicine.

It’s an embryonic institute, only recently formed by 42 physicians and scientists, several of whose names will be quite familiar to regular readers of SBM, but it’s jumping right into the fray. This is what the ISM is:

The ISM is a non-profit educational organization dedicated to promoting high standards of science in all areas of medicine and public health. We are a watchdog group of medical professionals who believe the best science available should be used to determine health policy and establish a standard of care that protects and promotes the public health. We oppose legislation that seeks to erode the science-based standard of care and expose the public to potentially fraudulent, worthless, or harmful medical practices or products.

Given how when faced with science going against them purveyors of unscientific medicine and medical beliefs try to win in politics where they can’t win in science (as my earlier post today describes for naturopaths in Ontario and the anti-vaccine movement in Oregon), just as we do on SBM, those of us who have helped to form the ISM have our work cut out for us.

Steve Novella has more.

Time and time again, we’ve seen it. When pseudoscientists and quacks can’t persuade the scientific and medical community of the validity of their claims, they go to the law to try to gain the legitimacy that their claims can’t garner through proving themselves by the scientific method. True, purveyors of pseudoscience and unscientifically-derived medical practices do crave the respectability of science. That’s why they try so hard to take on the trappings of science. The problem is that they just can’t do it right, try as they might, or when they do it right their methods are shown to be no more effective than a placebo, aside from the occasional seeming “positive” results that would be expected based on random chance alone. However, failing to achieve the respectability that the mantle of science provides, practitioners and advocates of pseudoscience frequently try to codify their woo into the law.

The reason that they would do this is not too hard to discern. Few legislators and politicians are scientists, and even fewer are scientifically inclined. Back when I still lived in New Jersey, I may have been lucky enough to have had a Congressional Representative who really was a rocket scientist (well, a physicist, actually), but now that I live in Michigan I’ve gone from having a scientifically inclined Congressional representative to having one of the dimmest bulbs in Congress representing me. What that means is that it’s far easier to persuade politicians that this woo or that woo deserves to be permitted or even licensed. That’s how we now have many states licensing acupuncturists, naturopaths, and even “homeopathic physicians,” as Arizona does. The pressure for this sort of acceptance of unscientific medical modalities is building, as well, as Kimball Atwood has documented. Another example is the Dietary Supplement Health and Education Act (DSHEA), which was passed in 1994 and in essence ties the FDA’s hands when it comes to regulating most supplements. Indeed, the very existence of the National Center for Complementary and Alternative Medicine (NCCAM) is a testament to the success of this approach, as a powerful Senator (Tom Harkin, D-IA) almost single-handedly foisted this scientific atrocity on the NIH against the desires of scientists. The results have included a $30 million scientific boondoggle of a trial to test chelation therapy and a profoundly unethical trial of Dr. Nicholas Gonzalez’s “protocol” for pancreatic cancer patients that a recent clinical trial has shown to be worse than useless. The most recent example of this trend is the way that CAM supporters have tried to hijack President Obama’s health insurance reform initiative to insert coverage for everything from any licensed “alternative medicine” practitioner to Christian Science prayer healing.

Recently, two new fronts have been opened up in this battle. One is disturbingly close to me, as it involves the Canadian province of Ontario whose north shore on the Detroit River is less than two and a half miles from my office, the other in Oregon, which, although it’s happening nearly 2,000 miles away from where I live and practice, could portend a new and disturbing tactic of the anti-vaccine movement to do what various other purveyors of pseudoscience have done before and try to win in state legislatures where they can’t win in science or the courts. Of course, in a democratic republic, it is the right of everyone, even supporters of quackery, to try to petition his or her legislators, but it is equally the responsibility of those of us supporting science-based medicine to try to educate legislators why allowing them to alter the law to protect their pseudoscience has the potential to result in great harm.

Naturopaths prescribing drugs?

I’ve never been able to figure out why naturopaths want to gain the power to be able to prescribe pharmaceutical drugs to patients. I really haven’t. After all, the entire philosophy of naturopathy as “finding and treating the cause of chronic problems, not just treating symptoms,” “letting nature heal,” and “treating the whole person,” whatever that means. Indeed, here’s what the American Association of Naturopathic Physicians says about naturopathic medicine:

First, do no harm. Naturopathic physicians follow three precepts to ensure their patients’ safety:

• Use low-risk procedures and healing compounds—such as dietary supplements, herbal extracts and homeopathy—with few or no side effects.
• When possible, do not suppress symptoms, which are the body’s efforts to self-heal. For example, the body may cook up a fever in reaction to a bacterial infection. Fever creates an inhospitable environment for the harmful bacteria, thereby destroying it. Of course, the naturopathic physician would not allow the fever to get dangerously high.
• Customize each diagnosis and treatment plan to fit each patient. We all heal in different ways and the naturopathic physician respects our differences.

Natural Standard defines a naturopath thusly:

Naturopathy is the practice of the use of natural substances to provide a healthier balance of internal chemistry.

A naturopath is a therapist who practices naturopathy. Naturopathic physicians (NDs) are primary healthcare practitioners. Naturopathic physicians are the highest trained practitioners in the broadest scope of naturopathic medical modalities. In addition to the basic medical sciences and conventional diagnostics, naturopathic education includes therapeutic nutrition, botanical medicine, homeopathy, natural childbirth, classical Chinese medicine, hydrotherapy, naturopathic manipulative therapy, pharmacology and minor surgery. Naturopathic practice excludes the use of most synthetic drugs and major surgery.

Naturopathic medicine is a natural and holistic approach to health and healing that recognizes the integrity of the whole person. Many treatment methods are used, including nutrition, herbs, manipulation of the body, exercise, stress reduction, and acupuncture.

It is not difficult to find naturopaths writing critical screeds against “big pharma” and the supposed evils of “allopathic medicine,” or the dismissal of “allopathic medicine” or “biomedicine” (one can almost see the sneer on the lips of the author writing that) as:

Human control over nature is characteristic of all Western Thought, including allopathic medicine. Since Descartes, matter has been considered separate from the spirit and the physical body, as part of matter, must be controlled for its own good. A physician is taught a “stewardship” view of the body that parallels society’s “stewardship” view of nature. It is well-intentioned, yet based on an attitude of control and domination. This is not to say that Biomedicine1 does not have its place. Rather, as we re-evaluate our relationship to the environment, we must necessarily re-evaluate our health care. “The ancient formula of one ill, one pill, one bill, which seems to have been the credo of physicians for many generations should be abandoned…Disease cannot be understood without an ecological study in depth [that includes] the environment, the host, and the culture”. Naturopathic medicine provides an alternative philosophy to Biomedicine that embodies environmental principles. These ecological tenets include finding deeper solutions than a technological fix, valuing diversity, accepting human limitations, trusting the Healing Power of Nature, and considering the ecosystem as a whole.

So why on earth would naturopaths want to prescribe pharmaceutical agents? It makes little sense, yet that is exactly what naturopaths are lobbying for in Ontario, as has been documented by Scott Gavura in the National Post and in the blog Skeptic North and Steve Thoms, as well as by our very own PalMD, Mark Crislip, and David Kroll. Worse, it appears that Ontario is poised to do just that and grant prescribing powers to naturopaths.

This would be a recipe for disaster. As we have discussed here many times, the key concept behind naturopathy is not scientific and the current movement for “naturopathic physicians” is in reality a resurrection of a 19th century health movement espousing the “healing power of nature.” Rather, at the heart of most naturopathic practices is primitive vitalism, a belief that has existed for hundreds, if not thousands, of years that there is a “life force” that can be manipulated for healing effect, an “energy” that modern medicines do not help. Many ancient health concepts derived from vitalism, such as the idea that disease is due to an imbalance of the “four humors.” It is the same concept behind reiki, acupuncture, and therapeutic touch, all of which are accepted and practiced by naturopaths. Another key belief behind naturopathy is that many diseases are due to “contamination” with “toxins,” which is why much of naturopathy concerns itself with “detoxification” regimens. Indeed, naturopathy is, more than anything else, a grab bag of virtually every implausible, unscientific, or even outright disproven “alternative” modality out there. It is not uncommon to see naturopaths offering colon cleanses, reiki, acupuncture, chelation therapy, and all manner of supplements. No woo is beyond the pale. Indeed, homeopathy is one major bit of quackery that is embraced by naturopaths.

Worse, as Scott Gavura and PalMD have argued, naturopaths do not have the knowledge base to be able to prescribe drugs safely. Indeed, Peter Lipson showed that quite conclusively when he issued a “primary care challenge” and quite correctly likened naturopathy for hypertension to “modern shamanism.” Their claims of treating the “whole patient,” notwithstanding, they do not have an adequate knowledge of how drugs work, what the potential side effects might be, or how various drugs might interact with each other or with the various supplements that naturopaths are fond of using. However, as we have seen in the past, pseudoscientific movements are nothing if not persistent and patient. After the Ontario government repudiated recommendations to allow naturopaths to prescribe drugs, the naturopaths are back and on the verge of persuading the Ontario legislature to give them what they want, as puzzling as it may be why they want it, given how much in conflict naturopathic philosophy seemingly is with “allopathic medicine.”

Maybe naturopaths have figured out that they can only go so far prescribing placebo medicine and ineffective modalities that can be outright dangerous, like chelation therapy and colon cleanses.

The anti-vaccine movement and “greening” Oregon’s vaccines

A less well-known but even more potentially dangerous example of purveyors of pseudoscience trying to influence government laws and policy is the anti-vaccine movement. It’s had some success and caused a great deal of mischief by successfully planting two of its own (Lynn Redwood, President of SafeMinds, and Lee Grossman, president and CEO of the Autism Society of America, both of whose organizations buy into the scientifically discredited notion that vaccines cause autism) on the Interagency Autism Coordinating Committee (IACC), where they have caused great mischief by constantly lobbying for a study of “vaccinated versus unvaccinated” children and in general trying to push the idea that vaccines cause autism, all helped by another anti-vaccine zealot, Mark “I’m a serious scientist, really” Blaxill, MBA, who blogs for Age of Autism. It’s also possible that anti-vaccine zealots had some role in the victory of “vaccine choice” supporter Chris Christie over Jon Corzine for governor of New Jersey, although, having recently lived in New Jersey, I’d say that it was far more Corzine’s incompetence than his stand on vaccines that led to his defeat earlier this month.

Other political and legal initiatives of the anti-vaccine movement have been much less successful. For example, for all the momentary attention it brought the movement, Jenny McCarthy’s and Jim Carrey’s “Green Our Vaccines” rally in Washington, DC last year resulted in no real concrete gains for the anti-vaccine agenda, try as various anti-vaccine activists might to point to use it for “momentum.” Later last year, after the election of Barack Obama, the efforts of Robert F. Kennedy, Jr. (whose masterpiece of cherry picking, Deadly Immunity, had stoked the flames of the anti-vaccine movement back in the summer of 2005) failed to persuade President Obama to give him a cabinet post in his administration. More recently, the Autism Omnibus, a huge class action legal appeal to the Vaccine Court, flamed out spectacularly, as the best “science” the movement could put forward was not enough to convince a special court that is plaintiff-friendly by design that “vaccine injury” can cause autism. Worse, this ruling came down in close temporal proximity to the revelation that a hero of the anti-vaccine movement, Andrew Wakefield, upon whom Age of Autism had bestowed its 2008 Galileo Award, had almost certainly–shall we say?–applied a bit too vigorous a “massage” to the “data” (if you can call it that) that he had used in his now infamous 1998 Lancet article allegedly linking the MMR vaccine to “autistic enterocolitis.”

Now, failing to convince using science, Generation Rescue, through its propaganda blog Age of Autism, is announcing a new initiative whose explicit intent is to try to enact an anti-vaccine agenda into law. This time, though, GR is much more clever about it than it may have been in the past. Gone are all those nasty and “inconvenient” signs among marchers at the “Green Our Vaccine” rally equating vaccines to toxic waste or even “weapons of mass destruction” and proclaiming that vaccines had “poisoned our son.” In its place are appeals to “informed consent” (the same ploy that the granddaddy of anti-vaccine groups, the NVIC, has used), for more “testing” of vaccines, and–of course–for the “vaxed versus unvaxed” study. GR’s plans are, in fact, laid out in detail for anyone to read in three posts by Kent Heckenlively:

• The “Green Our Vaccines” Initiative for Autism
• The “Green Vaccines” Initiative
• A Quick Guide to the “Green Vaccines” Initiative

Here is how Heckenlively describes the reason for this initiative:

I’d hoped the Special Masters of the Vaccine Court would put an end to the vaccine/autism catastrophe.  Nobody was more surprised than me by the decisions earlier this year in the cases of Cedillo, Hazlehurst, and Snyder.   
As an attorney I have great respect for the judicial system but the decisions struck me as terribly flawed.  Maybe I shouldn’t have been surprised.  The Vaccine Court isn’t really part of the traditional legal system.  It was a creation of the pharmaceutical companies to shield themselves from liability.  Why else would a plaintiff be unable to force a defendant to produce a single document or witness without the permission of the Special Master? These companies and the U. S. government know they have something to hide.

He’s even more explicit in the latest post:

We’re not going to get anywhere with our current legal system because everything gets funneled into Vaccine Court.  We’re not going to get far with the current media because they’re so heavily funded by pharmaceutical drug ads.  We’re not going to get far with the medical community because they’re part of the machinery.

And don’t even get me started on the politicians.  On one hand you have pharma handing out millions of dollars to politicians, and on the other you have parents of children with autism who are slowly bankrupted by this disease.  Who do you think is going to have more money to “support” the politician of their choice?

So what is this “initiative”? It’s an attempt to build a grassroots movement to persuade legislatures to pass legislation that ties in to the anti-vaccine agenda of Generation Rescue and similar groups. The proposals that this movement seeks to promote fall into five categories that GR wants to hire political consultants to “poll test” while at the same time wording them so that the pseudoscientific anti-vaccine agenda behind them is not obvious:

1. Research/Testing – Oregon requests the federal government to return the records of the Vaccine Safety Data-Link from private industry and make them available to independent researchers, conduct a study of vaccinated and unvaccinated children, study the health effects of aluminum adjuvants, and other substances used in vaccines like hydrolyzed gelatin and sorbitol.
2. Disclosure/Informed Consent – Comparison of Oregon schedules with that of the CDC and other first world countries and full disclosure of vaccine ingredients, as well as the level of safety testing on them.
3. Banning – Thimerosal ban across the board, as well as the flu shot for pregnant women, multiple vaccinations at a single visit, a six month ban on vaccines for premature births, and three months for any infant.
4. Changes to Existing Law – Adding a philosophical exemption for Oregon, reducing required vaccines, restriction of the Vaccine Act of 1986 to unavoidably unsafe components of vaccines, and additional rights of military personnel to choose alternative vaccination schedules.
5. Consumer/Parental Choice – Giving parents the freedom to choose aluminum and formaldehyde free vaccines, a different vaccination schedule, a titer check before vaccination, as well as one for mitochondrial disorders which might be exacerbated by a vaccine, and the right to have multiple vaccines such as MMR split up into individual doses.

How did Oregon get so lucky to be the “test state” for this initiative? Well, that’s where J.B. Handley lives. Sorry, Dr. Crislip.

That aside, it all sounds reasonable on the surface, doesn’t it? It’s particularly true if you don’t know the science behind vaccines, the anti-vaccine canards behind each of these five areas, and what these initiatives really mean. For example, it sounds so reasonable to open VSD data to “independent” researchers, doesn’t it? In fact, what GR really wants is for their pseudoscientists to be able to pick over the data and try to find spurious correlations. In fact, that’s just what happened when Mark and David Geier gained access to the VSD database in 2003, as Kathleen Seidel recounts. They went beyond what their IRB-approved research protocol allowed, tried to remove data, and as a result Kaiser Permanente’s IRB Administrator received a warning letter from the CDC about the Geiers’ attempts to merge datasets in a way that could compromise patient confidentiality. In reality, what GR wants is the opportunity for more anti-vaccine “researchers” to abuse the VSD as they have abused the VAERS database in order to produce dubious studies that claim to show a link between vaccines and autism. As for the call for a “vaccinated versus unvaccinated” study, I discussed that issue in detail a while back, and it’s worth reading again to see what the real agenda is behind calls for such a study, as well as to understand why such a study is not only impractical but superfluous.

The issue of disclosure and informed consent is also deceptive in that risks of vaccination are already disclosed and parents already have to give informed consent. The purpose of this item is to be able to play the “toxin” gambit by listing all sorts of scary-sounding ingredients in vaccines whose identity is already listed on the CDC website and to play up theoretical “risks” of autism that have not been scientifically validated, particularly the claim that the U.S. is “overvaccinated.”

The third item is particularly despicable, in my opinion. For one thing, the idea that thimerosal causes autism is a scientifically discredited hypothesis. For another thing, most childhood vaccines are already thimerosal-free, other than trace amounts, the exception being the flu vaccine. Finally, it’s the height of irresponsibility to call for banning the flu shot for pregnant women during the H1N1 pandemic. After all, they are one of the groups who are at increased risk for complications and can thus use the protection. Even worse is the call for a six month ban on vaccinating premature babies; premature babies arguably need protection even more than babies born after the normal period of gestation. There is no valid scientific justification for any of these proposals; more than anything else, they are born of the anti-vaccine movement’s fear and loathing of vaccines, and the proposal to ban multiple vaccines at a single visit is clearly custom-made to reduce the number of babies receiving all the currently recommended vaccines.

The last two proposals, I will admit, are clever. As I pointed out before, it’s far more attractive to frame one’s argument as being for something like “parental choice” than against something like life-saving vaccines. However, what these two proposals represent is an attempt by the anti-vaccine movement to legislate the standard of care to its wishes. Aluminum is safe and effective, with over an 80 year history of safe use, while removing formaldehyde from vaccines is totally unnecessary given that it’s a chemical that our own bodies make in quantities far greater than is in any vaccine. I once pointed out to Dr. Jay Gordon that he and his children are probably exposed to far more formaldehyde from auto exhaust when he sits in Los Angeles traffic than any vaccine contains. Moreover, formaldehyde is used for a specific purpose, namely to inactivate the virus being used for the vaccine. If formaldehyde weren’t used for that purpose, some other chemical, perhaps one not nearly as well-studied, would have to be used. Basically, what these last two proposals would do is to allow anti-vaccine activists to dictate the standard of care to physicians and to use basically any ingredient that they don’t like in vaccines as an excuse to refuse vaccines. It would also allow them to force doctors to order tests that aren’t routinely indicated, such as measuring antibody titers, or that are only very rarely indicated, such as tests for mitochondrial disorders because they mistakenly think mitochondrial diseases render children more likely to become autistic after vaccination. Apparently, such parents don’t mind subjecting their children to muscle biopsies for no good reason, because that’s what it sometimes takes to nail down a diagnosis of mitochondrial disorder. At the very least it takes a battery of other tests. It’s not a trivial matter and, because mitochondrial diseases are so uncommon, routine screening is far more likely to cause false positives than it is to be reliable.

Like naturopaths seeking prescribing privileges, the anti-vaccine movement has lost on the science. It can’t support its claims that vaccines cause autism or other neurolodevelopmental disorders, and it can’t validate the various “biomed” treatments that it promotes to “reverse vaccine injury” any more than naturopaths can show that their methods work reliably or that they have sufficient knowledge to be able to prescribe drugs safely. It’s all of a piece with many forms of pseudoscience, such as how it took a powerful Senator to ram NCCAM down the throats of NIH scientists, not based on any scientific merit or clamoring by the medical community for such a center but rather based on the raw political power of a woo-friendly politician.

Pseudoscientific movements are persistent and patient, too. If the naturopaths and Generation Rescue don’t get their wishes this time, they’ll be back again and again and again. Count on it. I liken them to casino interests in my city. Casino operators first started trying to get casinos into the city of Detroit at least three decades ago. Every time a measure was put on the ballot to allow them it was voted down. Casino owners just kept trying again and again and again, until several years ago they got what they wanted, probably thanks to the opening of casinos across the river in Windsor. A similar story played out in Ohio, where casino interests tried four times and failed four times to get the voters to allow casino gambling in Ohio before finally getting the votes they needed earlier this month. The analogy to casino gambling is an apt one, too. If states allow pseudoscience like that anti-vaccine movement or naturopaths to dictate medical policy and the standard of care, we will be indeed gambling with public health in a way as risky to medicine and health policy as walking into the MotorCity Casino is to $500 in a gambler’s pocket. The difference, of course, is that in the case of letting people like J.B. Handley there’s virtually no chance that we could win big–not even the same chance a one-armed bandit provides.