He was unvaccinated, but that was because of his age.  He was part of the population that is fully dependent on herd immunity for protection, and that is exquisitely prone to a life-threatening course once infected.  This is a topic we’ve covered ad nauseum, and I’m not inclined to go into greater depth in this post.  Suffice it to say his death is a failure at every level; we, both as medical professionals and as a society at large need to do a better job of protecting our children from preventable diseases.

Different approaches are required if we hope to improve our rates of vaccination.  Though we devote a great deal of time and effort on this blog addressing the various issues surrounding vaccination, none of us are so deluded (believe it or not) as to think that our posts will be persuasive to all of our readers, much less the general public.  In fact, I’d broaden that statement further, and say that the medical community in general is delusional if we think we can resolve the public health threat posed by the undercurrent of distrust in the vaccination program on our own.  No number of studies, consensus statements, or ad campaigns by the CDC, WHO, AAP, AAFP, etc (not to mention countless blog posts) will be sufficient to maintain the public trust in the vaccination program.  We need public support as well.

I’m not saying the work done by the medical community has been a wasted effort, far from it.  The vaccination program (along with the rest of modern medicine) must continue to be held to the highest possible scientific standard, we must perpetually re-examine our practice and recommendations, and we need to improve the communication between the public and medical communities.  These projects are absolutely essential.  However, the fact remains that no matter how strong the science may be, how large and uniform the expert consensus, how eloquent the argument, people are far more likely to be swayed by the opinion of a trusted friend, the actions of their peers, or the words of a celebrity, and we are fools to ignore that fact.*  Sometimes, different approaches are required.

Here is one example of a different approach: this Sunday, Penn & Teller’s “Bullshit” closed out their season by addressing the anti-vaccination movement.  Orac provided a review of the episode on Respectful Insolence, and I don’t have much to add to his analysis.  The show is characteristically blunt in their opinion, heavily slanted toward entertainment rather than informational content, and doesn’t shy from ad-hominems… in other words, you won’t find a transcript on SBM any time soon.  On the other hand, most of their arguments were sound, well grounded in science, and they didn’t even consider creating a false-balance.

I am certain Penn & Teller’s finale will do nothing to sway hardcore anti-vaccinationists, and its style is likely to turn off some others, but nevertheless the show has its place.  There is a fraction of the population for whom a blunt statement of fact and righteous anger (and Penn can provide both in spades) is exactly the type of presentation they need to see.

Here’s another example, and one that, while less flashy than Penn & Teller’s effort, is likely to have a broader appeal and greater impact in the long run.  In Atlanta, Georgia this September is a rather sizable (~40,000 people) convention called Dragon*Con.  Our skeptic friends at Skepchick.org and the newly formed “Women Thinking Free Foundation” are launching their their “Hug Me! I’m Vaccinated” education campaign at Dragon*Con, and have organized a local pertussis vaccination clinic during the event.  In coordination with the local health officials, they are providing free TDaP vaccinations for any Dragon*Con participant, as well as information and educational materials.**

I love this type of project.  As a public outreach effort Skepchick and Women Thinking Free Foundation are doing everything right by:

• Choosing to address an issue, pertussis, that is currently in the public eye
• Finding a venue with people from all over the nation (and world), thus reaching multiple communities with their message
• Coordinating with the local public health service to provide accurate information and safe services
• Targeting a population, primarily young adults, that represent a primary reservoir of pertussis and that have or will soon have children requiring vaccination
• Going out to the people to provide cost-free vaccines, thus eliminating the barriers that finances, a lack of access to health care, or even sheer apathy may present
• Providing a positive example as both parents and peers, and in doing so filling a gap in public communication the medical community can never fill on its own

That last point is perhaps the most important, and the easiest to emulate.  It doesn’t take access to a TV show or a Herculean effort to coordinate a vaccine drive to make a difference.  It doesn’t even require a confrontation.  You have more influence over the people in your life than any public health official or blog will ever have.  Just speak up, let people know you got your kids vaccinated today, let them know you got vaccinated!

As we strive to improve the quality of care and communication from the medical community, seeing concerned citizens stand up to make a difference in whatever way they can, no matter how large or small their sphere of influence, gives me hope.  Hope that maybe, just maybe, this might have been the last child I’ll ever fail to save from pertussis.

* I can see some accusing me of hypocrisy here for advocating the use of celebrity and personal anecdotes to provide support for vaccination.  It’s been said before, but let me be clear: Jenny McCarthy (as an example) is not wrong because she’s a celebrity, or a mother, because she’s not medically educated, or because she’s providing her own personal anecdotal experience.  She’s wrong because the basis for her arguments and anecdotes begins and ends at her celebrity/motherhood status instead of with facts and evidence; she is wrong because she misrepresents the state of objective reality.

** If you feel inclined to help, the Women Thinking Free Foundation is accepting donations on their website linked above to offset the cost of this and future outreach and educational projects.

The number of confirmed cases as of 6/30/2010 is growing rapidly (1,377), with an additional ~700 cases pending investigation.  General geographic location, ages, and ethnicity have been identified, and general vaccination rates and exemption rates are known, but other important demographic and epidemiologic data, including vaccination status of infected children and adults, has yet to be fully described.  Lack of data notwithstanding, I have read equally hasty stories and comments blaming the outbreak on vaccine refusal, a large immigrant population, an inadequate adult vaccination program, and normal cyclical variation in pertussis incidence, among other factors.  Finding where the system has broken down enough to allow this resurgence is exceedingly important, but in this situation pointing fingers is not as important as taking action.

Pertussis

A bit of background first.  Pertussis is a highly contagious infection of the respiratory tract by a bacteria Bordetella pertussis.  After an incubation period of 7-10 but up to 42 days, the disease progresses through three stages.  The catarrhal stage is often indistinguishable from the symptoms of the common cold, with runny nose, mild cough, and lasts 1-2 weeks.  During the second or “paroxysmal” stage infected people will have fits or “paroxysms” of uncontrollable rapid-fire coughing.  Examples can be seen here (caution, may be disturbing to watch). At the end of these paroxysms people take a large, rapid intake of breath through raw and often partially closed vocal cords, producing a high-pitched “whoop.”  The paroxysmal stage can last anywhere from 1-6 weeks.  The final stage is one of prolonged convalescence with a persistent dry cough lasting weeks to months (this is where pertussis got its other name, the “hundred day cough”).

A persistent cough isn’t the worst of pertussis.  60% of children under 6 months of age infected with pertussis need to be hospitalized, 5-10% get pneumonia, 1 in 125 have seizures, and 1 in 1000 suffer from an encephalopathy (inflammation of the brain) that frequently causes permanent brain damage.  And of course pertussis can kill.  Children under 3 months of age are at the greatest risk, and make up 84% of all pertussis related deaths.

Treatment is possible, but limited in utility.  Even though pertussis is bacterial and we have multiple antibiotics that reliably kill it, treatment after the first stage (when it becomes clear someone has more than a cold) only limits the ability of a person to spread it to others, it does not reduce the severity or length of the disease.  Once symptoms start, we are forced to ride out the illness.  Prevention is far better than treatment.  And speaking of prevention…

The Vaccine

The first vaccine to prevent pertussis was licensed in the US in the 1940s.  At that time we had an average yearly of 157 per 100,000 people, though this is likely to be a low-ball figure, given the state of medicine at the time and under-reporting.  From its release through the 1970s we saw a steady drop in cases from the pre-vaccination rate of 157 down to <1 infection per 100,000 people per year.  Though effective, the original vaccine had multiple side effects, including inducing a febrile seizure in 1 in 10,000 children.  These serious complications were enough to begin to undermine the public trust in the vaccine in the US, and to prompt several countries to stop pertussis immunization entirely.

In the 1980s and 90s several countries ceased or severely curtailed their use of DTP, including Japan, Sweden, and the UK.  Each of them saw a sharp and immediate rise in pertussis incidence to levels 10-100 times that of countries that continued to have high rates of vaccination with DTP.  This is a pattern we see repeated time and again when vaccines are withdrawn; it represents one of the best and most tragic demonstrations of vaccine efficacy you could ask for.

Effectiveness aside, the original DTP vaccine had legitimate problems, so a new vaccine was developed, tested, and eventually licensed for use.  By 1997 DTaP had fully replaced the original DTP vaccine.  Subsequent testing confirmed that it was just as effective as its predecessor, and induced significantly fewer side effects.  DTaP replaced DTP in the US before significant outbreaks could occur, and when instituted in countries that had stopped vaccination with DTP, quickly brought pertussis back under control.

DTaP, like all vaccines, continues to be studied, and is holding up very well to scrutiny.  Just this month, a self-controlled case series study in Pediatrics including 433,654 children and 7191 seizure events failed to find any significant association between DTaP and febrile seizures.

That the current pertussis vaccine is effective is beyond any serious contention, and its safety profile is excellent, but it’s not perfect.  The immune response the vaccine generates is relatively weak, necessitating multiple doses at 2, 4, 6, 15-18 months and 4-6 years to generate an adequate response (this isn’t unique to the vaccine; natural pertussis infection isn’t capable of providing long-lasting immunity either), and protection wanes after 5-10 years.

These characteristics predispose the vaccine, when used exclusively in childhood, to leave a couple of populations susceptible to infection.  First, the children most at risk of death from pertussis, those under the age of 3 months, have little to no direct protection from the vaccine or from maternal antibodies; this population relies heavily on herd immunity for protection.  The second vulnerability is that since neither the childhood vaccine nor natural infection provides lasting immunity, adults can become repeatedly infected, and serve as the primary reservoir of disease.  This is grimly illustrated by the fact that infants are most frequently infected not by other children, but by their parents.

Of course, this has been known for some time, and the vaccination schedule isn’t focused exclusively on early childhood.  A late childhood booster dose of TDaP (a reformulation of DTaP) at 11-18 years has been recommended since 2005, and adults are supposed to receive TDaP once between the ages of 19-64 to address this very problem.  Unfortunately, these doses are infrequently given for a variety of reasons, creating vulnerable populations to act as reservoirs for pertussis.

Though I may wish to have a vaccine that is somewhat less burdensome to use, it’s hard to complain about the current pertussis vaccine’s safety record, and properly administered, it’s capable of controlling and preventing epidemics (some even optimistically speculate the possibility of eradication).  To be fully effective though, it requires the dedicated support of both public health officials and the community.

The California Epidemic

Without a doubt, the relatively high-maintenance vaccination schedule contributes to our inability to fully control pertussis, but even if we had a vaccine capable of inducing lifelong immunity from birth onward, we would still have sections of the population that remain vulnerable to infection.  An embarrassingly large fraction of our fellow citizens lack access to health care.  Some immigrant populations may not have had the benefit of a modern medical system and immunization before arriving in the US, and some again lack access to health care after arrival.  A relatively small number of people are unable to be vaccinated or are immunocompromised due to medical conditions.  Finally, there are people who utilize California’s notoriously lax Personal Belief Exemption (PBE) policy to opt out of vaccination.

To what degree each of these factors is to blame for the current epidemic is not yet clear.  While it is true that some of the counties with the highest attack rates also happen to be counties where PBEs are common and vaccination rates low, other counties with reasonable vaccination rates are also being heavily affected.  (The attack rates of individual California counties can be found here.)  We simply do not yet have the entire epidemiologic picture, and it appears likely that several, if not all of these factors are in play.  That doesn’t mean, however, that we don’t know what action needs to be taken.

The California Department of Public Health is approaching this problem in the right way by addressing all of these elements at once, educating the public and expanding their TDaP program (TDaP program FAQ here, CDPH’s current activities and news releases here, and local California public health services here), though I think they may need to be even more aggressive.  In particular, I’d like to see a heavy revision of California’s PBE policy to make PBEs more difficult to obtain.

At the beginning of this post I said that in this pertussis epidemic, pointing fingers isn’t as important as taking action; to some this may have sounded hasty, but I hope you now understand my rationale.  An increase in size of any of any vulnerable group pushes the population as a whole closer to that nebulous cliff where herd immunity can no longer prevent an outbreak from becoming an epidemic.  No matter what the underlying cause(s) turns out to be, the single best intervention to control the spread of the current epidemic is the same: Vaccination. There may be multiple reasons for an outbreak of pertussis… but in our society there really is no excuse for it.

Sure enough, this week we admitted our first child of the year bitten by a venomous snake who, like most people unfortunate enough to be envenomated by a North American pit viper, has done very well.  This child fell prey not only to our local limbless fauna, but also to one of several common myths or misunderstandings about snakebites that place the victim, rescuer, or both at higher risk for injury and complications.  This post will explore some of the more common mistakes people make during North American snakebite encounters (being limited to snakes native to North America, the following does not necessarily apply to snakes from other areas).

File this post under Science-Based-You’re-Not-Helping-Please-Don’t-Do-That.

Myth #1: You Need to Know the Species / Kill the Snake

North America has around 120 species of snake, over 20 of which are venomous.  With so many species, it may seem important to ID the snake so the docs in the ED can give the appropriate anti-venin.  Fortunately, that isn’t the case.

All venomous North American snakes fall into one of two families, the Elapidae, and the Crotalinae.  Crotalinae encompasses most of the venomous species commonly encountered, including the Copperhead, the Cottonmouth (aka Water Moccasin), and all rattlesnakes.  Elapidae, on the other hand, is represented by only two species in North America, both a type of coral snake.

The close evolutionary relationship of these snakes (except the coral snake) means that the venom of all Crotalinae is very similar.  Venom is a mixture of a variety of different enzymatic proteins and low-molecular-weight polypeptides, in the case of Crotalinae including proteolytic enzymes, collagenase, hyaluronidase, phospholipases, RNase, DNase, phosphodiesterase, lactate dehydrogenase, a thrombin-like enzyme, and more.  It’s nasty stuff.

Though people have tried to label certain venoms as “hematotoxic” or “neurotoxic,” the sheer variety of proteins and their broad range of actions make this labeling somewhat misleading.  Symptoms and findings at the site of the bite include rapid swelling, bruising, pain, and erythema, while systemic symptoms include nausea, vomiting, oral paresthesias (odd sensations) including a metalic taste, low blood pressure, rapid heart rate and breathing, a markedly deranged ability of the blood to clot, kidney damage, altered levels of conciousness, weakness, double vision, and more.  The volume of venom and relative proportions of its component molecules vary species to species and snake to snake.  However, since the molecules themselves are so similar (and in many cases identical), a single antivenin is capable of treating the venom from all species within the family Crotalinae.

This fact mean clinicians need only ensure that the bite A) didn’t come from a zoo or private collection containing a non-North American venomous snake, and B) that it wasn’t a coral snake, before selecting which antivenin to administer.

How can a doc be sure someone wasn’t bitten by a coral snake?  After all, it does require a different and difficult to obtain antivenin from the Crotalinae. Here again we are assisted by happy chance.  Coral snakes have a very limited range, and can be ruled out in the majority of states.  In areas where the coral snake is endemic, it is easily identified by its red/yellow/black coloration at a distance.  Even an un-witnessed bite can frequently be distinguished by the symptoms and physical appearance of the bite on arrival.  Furthermore, coral snakebites while very serious are quite uncommon, making up only ~1% of venomous bites.

Physicians almost invariably have all the information they need to treat North American venomous snakebites from knowing the geographic location where the bite occurred and the patient’s history and physical exam.  No snake corpse is required or desired.

What’s the harm in killing the snake?  I’d think this was obvious were it not for the nearly ubiquitous element of snakebite histories that people went out of their way to kill the offending animal (the family this week did exactly that).  The risk of trying to kill a snake is that you can be bitten too.  Of all venomous snakebites, almost half occur while people are trying to kill a snake.  They place themselves at risk for no benefit to the person already bitten. Oh, and people will frequently then bring the “dead” snake in to the ED.  Is it dead?  Probably, but since the bite reflex can remain intact for a short time after death, I’d rather not risk my life on your skill as the Great White Hunter.

The best plan is to get everyone safely away from the snake and call animal control to get the animal away from your home, don’t try to do it yourself, and don’t bring it to the hospital.  Please.

Myth # 2: Most Snakebites are Rapidly Lethal

I remember speaking to a 12-year-old last year who was 2 days out from his bite and doing well, only to find that he still fully expected to die from the bite.  A snake, after all, had bitten him and snakebites kill you!  It broke my heart that I had allowed him to live with this fear for two days.

I should have anticipated his fear, because his reaction is not at all uncommon.  Most parents (and children old enough to know) are terrified when their child is bitten by a venomous snake.  Though entirely justified, their fears and expectations are usually out of proportion to the actual risk.

The lethality of a bite depends on a vast number of variables including the species and size of the snake, the location of the bite, the number, depth, and duration of bites, the first aid given, and the type and rapidity of medical care received.  In general, for Crotalinae envenomations not given antivenin the mortality is a very respectable 5-25%.

Antivenin (Crotalidae) Polyvalent (ACP) was the first antivenin introduced in 1954, and was produced by exposing horses to low doses of venom to induce antibodies against its component molecules.  IgG antibodies, including those now directed against the venom, were then purified from the horse’s blood and this was injected into humans bitten by Crotalinae species.  The antibodies then bind to the various proteins and enzymes in the venom, rendering them inert.  The use of this antivenin reduced the mortality rate from 5-25% down to 0.5%.

Though effective, ACP had a rather high incidence of anaphylaxis (20-25%) and serum sickness (~50%), driving the development of a better antivenin.  In 2000, CroFab was approved.  Derived from sheep serum, containing far less non-human protein, and being made of a Fab fragment, Crotalidae Polyvalent Immune Fab (Ovine) aka CroFab, has been far better tolerated.  Post-release studies have reported anaphylaxis or severe reactions in 0-19%, and serums sickness in 0-23%, and mortality rates are the lowest they have ever been.  CroFab is currently the only Crotalidae antivenin available.

Presently there are around 8000 venomous bites per year in the US, but less than 12 deaths per year, making current mortality ~0.15%, though another 15-40% of victims sustain some form of permanent injury or disfigurement.

In addition to the fact that most bites are from non-venomous snakes, there is another facet to snakebite lethality to think about: the concept of a  “dry bite,” or a bite from a venomous snake without injection of venom.  It’s surprisingly common, accounting for around 25% of Crotalinae bites and ~50% of coral snake bites.  Given the high rate of dry bites from venomous snakes, large number of bites from non-venomous snakes, and the rather high side-effect profile of even our newest antivenin, it’s reasonable to ask who should get antivenin.

If you have symptoms of envenomation, you need antivenin, period.  However, symptom onset can be delayed, occasionally by hours.  If someone arrives in the ED with a bite but no symptoms other than a couple of small holes, it is reasonable (and standard of care) to watch them in the ED without antivenin.  Should symptoms begin, antivenin should be started immediately, but if there are no symptoms after 12 hours, it is safe to declare the encounter a dry bite, the person lucky, and let them go home.

Remember, all snakebites should be taken seriously and brought to immediate medical attention, but most will not require antivenin, and even those who do will tend to recover well.

Myth # 3: Suck Out the Poison

I love this one.  The idea is self-apparent: venom is in me, I want venom out of me, suck it out through the holes.  You’ve seen it in countless Old West movies, and it still pops up in modern entertainment, older medical literature, and even some out of date professional sites.  There are devices currently marketed to apply a constant negative pressure (~ 1 atmosphere) to the wound and actually do produce fluid, purportedly containing venom, that is then discarded.  As recently as the early 2000’s, these devices were advocated for short durations of time as they were felt to hold some potential benefit but pose little risk of harm.  Time and study has not been kind to this recommendation.

First the question of efficacy.  After needle injection of a radio-labeled fluid into volunteers, one study attempted to then remove it by suction using a popular commercially available pump; they successfully removed only 0.04% of the simulated venom.  In another randomized, controlled study pigs were randomized to receive suction therapy or no suction following injection of real venom.  The suction pump effected no improvement in symptoms in the pigs.  The bulk of the evidence, sparse as it is, indicates that these devices do not work.

Beyond being ineffective, suction devices also cause quite a bit of damage.  Even on normal skin negative pressure quickly forms a “hickey,” which is a bruising and edema of the skin.  Combine that trauma with skin being actively destroyed by the venom, and you simply generate a worse wound without reducing the venom load.  This is precisely what was found in the porcine study discussed earlier, and has been reported in the literature since. Significant harm + no benefit = bad idea.

Suction applied by mouth is even worse.  Not only does it just as ineffective while carrying the same risk as the devices (maybe a bit less, since the suction isn’t sustained), but now you add the oral bacterial flora of the human mouth to a fresh wound.  Snakes’ mouths are far from sterile, but bacterial infections after snakebites are uncommon enough (<3%) that antibiotics are not routinely prescribed, unlike human bite wounds.  Don’t compound the problem by giving the victim cellulitis.

If you are bitten by a snake and someone tries to suck out the poison, kindly go ask them to catch the snake instead.*

* Don’t do that.  Just tell them to call 911.

Myth # 4: Place a Tourniquet

In older survival manuals it was common advice to apply a tourniquet around the bitten limb, the thought being to limit the venom’s spread and to provide time to get to medical care.

There has been at least one animal study that demonstrated a longer survival time in pigs after envenomation with the use of a tourniquet (36 min longer), providing some plausibility to the benefit of tourniquets after snakebites.  However, the same study also showed markedly elevated pressure in the effected limb (43 mmHg higher) and led the authors to discourage the use of tourniquets for snakebites. But better to lose a limb and save a life, right?  Well, yes, if it were effective at saving lives in practice.

The trouble is that in practice tourniquets are fiendishly tricky to apply without causing further injury, and even with training under controlled circumstances professionals aren’t able to place them to the “proper” pressure.  Furthermore, clinical studies have failed to confirm the modest benefit seen in one animal model while demonstrating multiple serious complications from their use (tourniquets too easily become ligatures and compound the injury of the venom).

Tourniquets have their place in medicine, but it isn’t in the management of a venomous snakebite.

Myth # 5: Apply Ice

One of the hallmarks of a Crotalinae envenomation is swelling, pain, bruising, and often a burning sensation.  This superficially resembles other traumatic injuries, like a badly twisted ankle commonly treated with ice packs, so it makes some sense people are inclined to try cooling a snakebite.

Though there is a degree of hyperemia (increased blood flow) with envenomations that ice will reduce, the swelling is due more to the direct tissue injury of the venom. That direct injury also causes increasing pressure, clotting, and vascular damage all of which impede and at times stop blood flow to the tissue.  Anything done that further reduces blood flow (like ice or tourniquets) can make such injuries much worse.  Animal modeling has failed to show a benefit from cooling of the injury, and clinical studies have suggested that people may have more complications if their bites are iced.

There is, of course, also the more obvious risk of ice, in that it tends to be rather cold, and can cause injury to even healthy tissue if not closely monitored.  Yet again, we have little hope of benefit with clear risk of harm.  No ice.

Myth # 6: Taze Me, Bro! (Electrotherapy)

In 1986 the Lancet published the first paper in the medical literature where Dr. Guderian advocated high voltage electric shock of the envenomated site as a first aid technique. Subsequent studies in both animals and humans failed to show any benefit, and there has not been any significant presence of this intervention in the medical literature since 2001, which was a paper condemning its use.

Of course, this hasn’t stopped people from adding insult to injury by tazing their buddies who were just struck by a rattlesnake.  Yes, really.  Let that image sink in for a moment… there you go.  Dr. Guderian, or someone posing as him, puts forth the argument for electrotherapy of envenomations here.  As this is already a lengthy post, I’ll address this gem of a site and its specific claims at a later time.  Suffice it to say that beyond a very crude form of pain control, electrotherapy holds no plausible benefit, has significant risk of harm (like electrocution and burns), and has the existing literature stacked firmly against it.

If you are bitten by a snake and someone tries to taze you, kindly go ask them to go catch and taze the snake instead.*

* Again, don’t do that.  Just tell them to call 911, then re-assess your choice of friends.

What You Should Do

Odds are that neither you nor anyone you know will ever be bitten by a snake.  However, if you happen to find yourself joining those unlucky few, the best things you can do are incredibly simple:

1)    Calm the victim and calm yourself.

2)    Call 911.

3)    Immobilize the limb like you would a fracture and await medical assistance.

4)    Report any symptoms, no matter how odd or minor, to medical providers immediately as they occur.

What if you are days out in the wilderness, is it worth trying these interventions in a desperate situation?  No.  Being away from help doesn’t make useless and harmful interventions any less useless or harmful.  Instead, be responsible and have an evacuation plan for any medical emergency, including snakebites.  Now go enjoy the Spring!

It was with trepidation, then, that I waited to see how PBS’s Frontline handled the topic of vaccination.  I was pleasantly surprised.  “The Vaccine War” introduced the most common concerns expressed about vaccination, and then presented the evidence addressing each concern in turn clearly and concisely.  It gave airtime to some rather prominent anti-vaccine personalities, but the bulk of the program was dedicated to the data, the science, the evidence, and where answers are available it did not hesitate to present them baldly and clearly. “The Vaccine War” was not a comprehensive review of every perspective, every theory, every vaccine and study, but it did provide a fair discussion balanced by the science.

My first clue that Frontline had acquitted itself well was when Dr. Jay Gordon, pediatrician to Jenny McCarthy’s son, tweeted his opinion of the show:

PBS show about vaccines. Don’t bother to watch it.”

Dr. Gordon wasted no time venting his outrage at the show’s message, its tone, and the fact that he was cut from the program at The Huffington Post.  I encourage you to read the original at The Huffington Post, and to post your own comments.  I will discuss his points here in detail, providing the periodic reality check.

Dear Kate,

The Frontline show was disgraceful. You didn’t even have the courtesy to put my interview or any part of the two hours we spent taping on your web site.

Dr. Gordon was interviewed, and his contribution was not felt to provide value to the  program.  He was cut.  That is the prerogative of the producers, and they are under no obligation to include Dr. Gordon just because he was interviewed.  If he is unhappy with his treatment, he is more than welcome to decline the next interview.  In fact, I think that would be an excellent idea.

You created a pseudo-documentary with a preconceived set of conclusions: “Irresponsible moms against science” was an easy takeaway from the show.”

Dr. Gordon needs to review the definitions of “pseudo” and “documentary.”  Is a WWII program on the History channel a pseudo-documentary because it covers the war from the Allied perspective?  Of course not, it provides facts within a context, a narrative; this is essential in a documentary, and it is precisely what the producers of this program have done.  That the producers decided to provide a story based upon facts and science determined the conclusions they presented.

Did you happen to notice that Vanessa, the child critically ill with pertussis, was not intubated nor on a respirator in the ER? She had nasal “prongs” delivering oxygen. I’m sorry for her parents anxiety and very happy that she was cured of pertussis. But to use anecdotal reports like this as science is irresponsible and merely served the needs of the doctor you wanted to feature.”

This objection by Dr Gordon is petty, appalling, and hypocritical.  So what if she wasn’t intubated?  This is a suffering infant who is critically ill and will remain so for weeks.  Is her suffering not worth preventing just because she didn’t die?  Is that how low Dr. Gordon sets his threshold for a child warranting medical care?  This is appallingly callous.

The segment that portrayed vaccine preventable diseases, including the segment with pertussis, was explicitly stated by the program to demonstrate what these diseases look like to a population that, on the whole, has never seen them.  How else would Dr. Gordon propose to provide this information to the public?  This is an entirely appropriate use of an anecdote, as an example of the evidence, rather than as the evidence itself.

Furthermore, by Dr. Gordon’s own admission, the producers did not provide the worst-case scenarios of each of these diseases, all of which can be fatal, though they could easily have done so if their goal was purely emotional manipulation, rather than education of legitimate risks of these diseases.

No one pursued Dr. Offit’s response about becoming rich from the vaccine he invented. He was allowed to slide right by that question without any follow up. Dr. Paul Offit did not go into vaccine research to get rich. He is a scientist motivated by his desire to help children. But his profiting tens of millions of dollars from the creation of this vaccine and the pursuit of sales of this and other vaccines is definitely not what he says it is. His many millions “don’t matter” he says. And you let it go.”

I am glad to read Dr Gordon acknowledge that Dr Offit’s motivation to research and produce vaccines was not financial.  He is a professional who produced an excellent and badly needed vaccine to prevent a nasty disease.  Excellence in our society is usually rewarded with financial compensation.  So what?  The research that led to Offit’s rotavirus vaccine, the data supporting its safety and efficacy before licensure, and the volume of post-licensure safety and efficacy data replicated by other researchers stands on its own whether Dr Offit is penniless or a billionaire.

Jenny McCarthy resumed being a “former Playboy” person and was not acknowledged as a successful author, actress and mother exploring every possible avenue to treating her own son and the children of tens of thousands of other families.”

Frontline is not obliged to present a full CV on each person appearing in its program, and Ms. McCarthy’s role as a former Playmate is both factual and the original source of her fame.  Dr. Gordon’s perspective heavily biases his description of her as a “mother exploring every possible avenue to treating her own son and the children of tens of thousands of other families”.  She could just as easily (and perhaps more accurately) be described as a mother who, in pursuing her own ill-founded beliefs, has undermined the care of her child, placed him at higher risk of preventable disease, subjected him to worthless therapies while ignoring known serious risks, used her celebrity to disseminate misinformation and fear to the public while simultaneously diverting research time, energy and funds away from fruitful avenues of study, and delaying the time when the tens of thousands of families can better understand autism and be provided with more viable therapies.  Oh, and Frontline could have mentioned her foray into the embarrassing “Indigo Child” nonsense.  Perhaps describing her as a “former Playboy” isn’t so bad.

I trusted you by giving you two or three hours of my time for an interview and multiple background discussions. I expressed my heartfelt reservations about both vaccines and the polarizing of this issue into “pro-vaccine” and “anti-vaccine” camps. I told you that there was at least a third “camp.” There are many doctors and even more parents who would like a more judicious approach to immunization. Give vaccines later, slower and with an individualized approach as we do in every other area of medicine.”

This is a straw man.  No one, even the most staunch vaccine advocates, advocate the identical vaccination regimen for every child.  There are uncommon but clear reasons to deviate from the vaccination schedule due to a child’s individual medical history.  However, these are based upon evidence, not the arbitrary judgment of individual physicians.

What evidence does Dr. Gordon provide that later, slower, individualized vaccination schedules do anything but reduce the herd immunity of a community, increase the number of doctor visits, decrease the likelihood that a child will be fully immunized, or increase the time for which a child is unprotected?  No such evidence exists, so one must wonder on what he has based this recommendation.

The “individualized approach” to medicine warrants a series of posts all to its own. Suffice it to say that while there are uncommon times when a patient’s care must deviate from the usual approach, standardization of care is one of the most effective ways of improving patient outcomes, and is one of the pillars of evidence-based (and science-based) medicine.  “Every other area of medicine” is making its best advances through the standardization of medical care, not capricious, evidence-free judgment calls of individual physicians.

What did you create instead?

“The Vaccine War.”

A war. Not a discussion or a disagreement over facts and opinions, but a war. This show was unintelligent, dangerous and completely lacking in the balance that you promised me — and your viewers — when you produced and advertised this piece of biased unscientific journalism. “Tabloid journalism” I believe is the epithet often used. Even a good tabloid journalist could see through the screed you’ve presented.”

And I believe this is one of the better examples of “projection” that I’ve come across.  I touched on the idea of “balance” in journalism at the beginning, and will not rehash it here.

You interviewed me, you spent hours with Dr. Robert Sears of the deservedly-illustrious Sears family and you spoke to other doctors who support parents in their desire to find out what went wrong and why it’s going wrong and what we might do to prevent this true epidemic.”

Dr. Gordon sets up a false-dichotomy here.  He pretends that only physicians who believe vaccines cause autism support parents of autistic children, or want to find the root cause of autism, or to find viable treatments or ways to prevent it.  This is absurd.

How deserving Dr. Sears is of his popularity we have addressed on SBM in the past, and can be found here.

Not a measles epidemic, not whooping cough. Autism. An epidemic caused by environmental triggers acting on genetic predisposition. The science is there and the evidence of harm is there.”

Autism diagnoses are higher than they have been in the past, and they are unsettlingly common, warranting a large-scale research, therapeutic, and support system that is currently lacking.  This is due in large part to increased awareness and broadened definitions of what places someone on the autism spectrum, though the possibility of a smaller scale true increase in the incidence of autism has not yet been confirmed or ruled out.  To label this as a “true epidemic” is inaccurate on several fronts.

Dr. Gordon is correct that autism has an indisputable genetic predisposition.  However, to what degree environmental triggers play a role, and which triggers these may be have not been established.  The science is there, but it does not come remotely close to supporting Dr. Gordon’s statement.

Most importantly, the evidence of harm, of vaccines causing autism, is not only not there, but the evidence overwhelmingly demonstrates no correlation between vaccines and autism.

Proof will come over the next decade.”

Oh, so Dr. Gordon doesn’t have proof now.  Thank you for clarifying.

The National Children’s Study will, perhaps by accident, become a prospective look at many children with and without vaccines. But we don’t have time to wait for the results of this twenty-one year research study:”

“We don’t have time to wait” The same can be said of every single medical condition suffered by a human being.  This doesn’t minimize their suffering, it drives home the point that we must perform the highest quality science possible and reject hypotheses that have been found to be without merit.  The proposed vaccine/autism link is one such hypothesis.

We know that certain pesticides cause cancer and we know that flame retardants in children’s pajamas are dangerous. We are cleaning up our air and water slowly and parents know which paint to buy and which to leave on the shelves when they paint their babies’ bedrooms.”

Where such statements are true they were found and confirmed by scientific inquiry, and when they are false they are refuted by the same method.  Belief and opinions are irrelevant when objective data is available, and the above paragraph is an irrelevant distraction to the topic of Dr. Gordon’s letter.

The information parents and doctors don’t have is contained in the huge question mark about the number of vaccines, the way we vaccinate and the dramatic increase in autism, ADD/ADHD, childhood depression and more. We pretend to have proof of harm or proof of no harm when what we really have is a large series of very important unanswered questions.”

That we don’t have the answers to everything does not mean that we don’t have the answers to anything, nor does it give us license to ignore the evidence we do have.

In cased you were wondering, as I practice pediatrics every day of my career, I base nothing I do on Dr. Wakefield’s research or on Jenny McCarthy’s opinions. I respect what they both have done and respectfully disagree with them at times. I don’t think that Dr. Wakefield’s study proved anything except that we need to look harder at his hypothesis.”

Case in point.  We have looked harder at Dr. Wakefield’s hypothesis, and it has failed catastrophically.  With no evidence in its favor and much against, Dr. Gordon has yet to reject Dr Wakefield’s hypothesis.

Of equal interest, is Dr. Gordon willing to acknowledge that the original paper Dr Wakefield published in The Lancet is at best a scientific embarrassment?

I don’t think that Jenny McCarthy has all the answers to treating or preventing autism but there are tens of thousands of parents who have long needed her strong high-profile voice to draw attention to their families’ needs: Most families with autism get inadequate reimbursement for their huge annual expenses and very little respect from the insurance industry, the government or the medical community. Jenny has demanded that a brighter light be shone on their circumstances, their frustration and their needs.”

I actually agree with Dr. Gordon here.  Autism is indeed a widespread problem badly in need of high-quality research, and families are in dire need of support.  It is unfortunate that the advocate they have found was so badly misguided by her pediatrician.  Dr Gordon was in the position to guide her, to educate her, connected her with experts in childhood development and autism and enable her to use her enthusiasm and desire to help her son and the rest of the autistic community.  Unfortunately, Dr Gordon squandered this opportunity, to the detriment of us all.

I base everything I do on my reading of CDC and World Health Organization statistics about disease incidence in the United States and elsewhere.”

Dr. Gordon claims that he bases his decisions on evidence.  Yet he has come to different conclusions from those who generated the evidence, and those who are experts in the field.  Only one group can be right, and neither the evidence nor the odds are in his favor.

I base everything I do on having spent the past thirty years in pediatric practice watching tens of thousands of children get vaccines, not get vaccines and the differences I see.”

Experience has value, but it is little more than a long series of anecdotes, and as such it can also be a trap.  Nearly every modern physician can make a similar statement, as can every homeopath, acupuncturist, phrenologist, faith healer and shaman.  Placing personal experience, no matter how vast, above solid objective data is a hallmark of someone practicing pseudoscience, and it is precisely this sin that Dr. Gordon commits.

Vaccines change children.”

An assertion made without evidence can be rejected without evidence.  Dr. Gordon clearly feels he has discovered new information, a previously unidentified pattern, yet he has not even bothered to publish a simple case series to try to convince the medical community of his claim.  Making such a statement without evidence is irresponsible.

Most experts would argue that the changes are unequivocally good. My experience and three decades of observation and study tell me otherwise.”

Again, Dr. Gordon feels his experience trumps evidence.

Vaccines are neither all good–as this biased, miserable PBS treacle would have you believe–nor all bad as the strident anti-vaccine camp argues.”

This is another straw-man by Dr. Gordon.  The program clearly acknowledges the presence of adverse events from vaccines, including extremely serious ones.  No one, including the producers of “The Vaccine War,” claim that vaccines are “all good.”  But the benefits do clearly outweigh the risks.

You say the decisions to edit 100% of my interview from your show (and omit my comments from your website) “were purely based on what’s best for the show, not personal or political, and the others who didn’t make it came from both sides of the vaccine debate.” You are not telling the truth. You had a point to prove and removed material from your show which made the narrative balanced. “Distraught, confused moms against important, well-spoken calm doctors” was your narrative with a deep sure voice to, literally, narrate the entire artifice.

You should be ashamed of yourself, Kate. You knew what you put on the air was slanted and you cheated the viewers out of an opportunity for education and information. You cheated me out of hours of time, betrayed my trust and then you wasted an hour of PBS airtime. Shame on you.”

As Dr. Gordon draws his rant to a close, he returns to telling a PBS producer how to do her job.  He does not, however, at any time provide any evidence to contradict a single pertinent point or piece of evidence made in the entire hour of “The Vaccine War.”

The way vaccines are manufactured and administered right now in 2010 makes vaccines and their ingredients part of the group of toxins which have led to a huge increase in childhood diseases including autism. Your show made parents’ decisions harder and did nothing except regurgitate old news.

Parents and children deserve far better from PBS.”

How can Dr. Gordon write the preceding paragraph and then claim to be anything other than anti-vaccine? PBS is not the one to be ashamed; our children deserve better stewardship than that of Dr. Jay Gordon.

Of course, most of this has not been news in the literal sense of the word.  There hasn’t been anything truly new in homeopathy since its invention (no, not discovery; discovery implies that something actually exists to be found) by Hahnemann in 1796.

Well, perhaps that’s not quite fair.  As our knowledge of reality (medicine, pharmacology, chemistry, physics, etc) has steadily improved, homeopathy’s plausibility has dwindled to the point of being indistinguishable from the roundest of numbers (0).  And I suppose the recent contortions of logic, abuses of legitimate science, and pure magical thinking put forth to protect homeopathy from the relentless assault of science are far more impressive than that laid out by Hahnemann.  So that’s news of a sort.

There’s also homeopathy’s long and rich tradition of abject failure in randomized controlled trials to consider.  The overwhelming mountain of evidence showing homeopathy to have no effect beyond placebo is impressive and definitive.  That’s data Hahnemann didn’t have, so that’s news too.

Each of these properly conducted studies and analyses demonstrates the scientific method’s utility to help us understand reality and protect us from our own delusions, but frankly, at this point they are about as exciting and useful as proving that the sun will rise in the east tomorrow morning.  News?  Not so much.

Nuremberg’s Less Famous Trial

I found myself wondering how far back this trail of negative trials goes; how long we’ve been having the identical argument.  Pubmed’s earliest mention of homeopathy was in 1906, and the first RCT I found in its database was in 1980.  However, the oldest double-blind RCT of which I found record was conducted in 1835 in Nuremberg, Bavaria, and subsequently described in an editorial in 2006 entitled “Inventing the randomized double-blind trial: The Nuremberg salt test of 1835.” Though the trial has its flaws, it was of sufficient quality to satisfy my historical curiosity with a thoroughly depressing answer: 175 years.

The local physicians and public health officials of Nuremberg held an understandably dim view of homeopathy, and as it gained popularity in Nuremburg they became more vocal, and more public, in their opposition:

Von Hoven accused homeopathy of lacking any scientific foundation. He suggested that homeopathic drugs were not real medicines at all and alleged homeopathic cures were either due to dietetic regimens and the healing powers of nature, or showed the power of belief. He called for an objective, comparative assessment by impartial experts. If, as he expected, homeopathic treatment proved ineffective, the government would need to take drastic measures to protect the lives of deceived patients.”

Sounds familiar, doesn’t it?  Nuremburg’s resident homeopath Karl Prue’s defense should as well:

[Prue] pointed out that even children, lunatics and animals had been successfully cured. Based on Hahnemann’s assertions, he challenged Wahrhold/von Hoven to try the effects of a C30 dilution of salt on himself. The odds were 10 to 1, he claimed, that his opponent would experience some extraordinary sensations as a result – and these were nothing compared to the much stronger effects on the sick.”

Eventually a trial was designed and agreed upon by both parties to test the effect of a 30C dilution of salt.  The trial design was surprisingly good, as it was:

• Randomized: participants had an equal chance of being in either the control or experimental group
• Controlled: participants not given the experimental therapy were given an indistinguishable and inert placebo
• Blinded: participants didn’t know if they received the homeopathic dilution or placebo
• Double-blinded: the experimenters didn’t know which participants received the homeopathic dilution or placebo, as the placebo and homeopathic dilution were prepared and the vials containing them randomized and coded by people independent from the experimenters.
• Well Powered: the trial contained enough participants so that if, as Prue claimed “the odds were 10 to 1… to experience some extraordinary sensations” that it could detect a difference between the two groups.
• Transparent: The design, hypothesis, methods and outcomes were agreed upon beforehand and explained in detail to all participants, conducted publicly (in a literal Pub in fact; these people were full of good ideas), results were published quickly, and any deviation from protocol was acknowledged.

Of the 54 people they managed to enroll, 50 completed the study three weeks later by reporting what, if any, “extraordinary sensations” they had experienced following ingestion of their vial.  5 people reported sensations in the homeopathic group, 3 in the control, which was statistically insignificant.  Homeopathy had failed the first of many RCTs.

I am not putting this trial forward as the final (though perhaps it could be considered one of the first) nail in homeopathy’s coffin.  The trial design had areas of potential bias, most notably that the symptoms which qualified as “extraordinary” are not well defined (though a glance at the homeopathic proving of “Natrum Muriaticum” or “table salt” provides some insight into this particular problem), and the fact that it relied upon participants to honestly report all symptoms; a hostile or imperceptive set of participants could easily confound the study.  Nevertheless, on the whole it was solidly designed and executed, particularly when one considers that this is one of the first double-blind, randomized controlled trials ever documented.

Time To Move On

Here we are in 2010, 175 years after the first of legion negative RCTs of homeopathy, yet it persists with the same tired old arguments.  Is there anything to gain from investing more time, money, resources, and ignoring the highly dubious ethics of subjecting human subjects to a trial that has no hope of benefiting them or humanity, just to prove one more time that homeopathy is an utter failure?  No, and here’s why.

I look at the current debate surrounding homeopathy, and I see three primary groups.  The first accepts the last two centuries of scientific progress and evidence and concludes that homeopathy is a delusion unworthy of further study.  They don’t need another trial.

The second believes in homeopathy in spite of the gargantuan volume of evidence; further evidence will do nothing to change their minds.  They don’t need another trial.

The final group is comprised of people who are unaware of the nature of homeopathy or the evidence that already exists.  This final group requires exposure and education; they require World Homeopathy Awareness Week (SBM edition).  They don’t need another trial.

Nothing seems to personify the evil of modern medicine to Dr Mercola more than the concept of vaccination, and Gardasil, the vaccine against human papillomavirus (HPV), has been drawing a good deal of his ire of late.  Case in point is this train-wreck of a post comparing the recent Toyota recall to Gardasil entitled “Time for the Truth About Gardasil.”  The post is ill-named.

It begins:

Cervical cancer accounts for less than 1 percent of all cancer deaths — so it was somewhat surprising when the U.S. Food and Drug Administration fast-tracked approval of Gardasil, a Merck vaccine targeting the human papilloma virus that causes the disease.

Cervical cancer tallied 11,982 new cases of cervical cancer and 3,976 deaths in 2006, not to mention the non-cervical cancers for which it is also responsible.  Worldwide it has an even greater impact as the second leading cause of cancer in women.  Unless Dr Mercola is trying to tell us that he considers the prevention of several thousand deaths per year in the US alone a waste of effort, the fact that cervical cancer isn’t one of the leading causes of cancer death in the US is irrelevant to the FDA’s approval of Gardasil.

I’m certain the actual point Dr Mercola is trying to make is that in his opinion, Gardasil was inadequately tested prior to release, and that he does not accept the data supporting its efficacy or safety.  The fact is that it was tested on over 20,000 women in stage 3 trials where both its safety and efficacy profiles were excellent while identifying a few rare but legitimate side effects, and that post-licensure studies after over 23 million doses have supported the original licensure data (I covered this topic at some length here, as has Dr David Gorski here).  If Dr Mercola insists on having such exceedingly high standards for the safety and efficacy of a vaccine, surely he holds the myriad concoctions and other products he endorses and sells on his site to the same standard.  Surely.  Right.

He then continues:

As of the end of January 2010, 49 unexplained deaths following Gardasil injections have been reported to the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System.

Mercola implies that the 49 “unexplained” deaths are in fact due to Gardasil (there were 48, not 49 on my check on April 2^nd, 2010).  There are two major problems with this statement.  First and foremost, an unexplained death is, by definition, unexplained.

Second, of the deaths associated with Gardasil reported to CDC’s VAERS, the majority of them are explained.  At the time of the post-licensure review published in JAMA in August of 2009, there had been 32 deaths reported following Gardasil injection occurring between 2 to 405 days after the last injection. This is the breakdown of those 32 reported deaths after investigation:

Eight of the reports were second-hand reports that could not be verified. Four were manufacturer reports with no identifying information for confirmation or medical review… Causes of death (of the remaining 20) included 4 unexplained deaths, 2 cases of diabetic ketoacidosis (1 complicated by pulmonary embolism), 1 case related to prescription drug abuse, 1 case of juvenile amyotropic lateral sclerosis, 1 case of meningoencephalitis (Neisseria meningitidis serogroup B), 1 case of influenza B viral sepsis, 3 cases of pulmonary embolism (1 associated with hyperviscosity due to diabetic ketoacidosis), 6 cardiac-related deaths (4 arrhythmias and 2 cases of myocarditis), and 2 cases due to idiopathic seizure disorder.

Keep in mind that over 23 million doses of Gardasil had been administered in the US at this point.  It would be remarkable if none of those millions of women had died within a year or so of receiving the vaccine.  A rate of death similar to that of the control population with a random smattering of causes should be expected, and is exactly what is found.  As always, correlation does not necessarily mean causation, and Dr Mercola is deprived of his greatest source of rhetoric against Gardasil.

Not that it will stop him from jumping another shark:

By contrast, 52 deaths are attributed to unintended acceleration in Toyotas, which triggered a $2 billion recall.

Holy false analogy, Batman!  He’s comparing apples to… I don’t know, mops or something.  Where to begin?  Let’s just accept the number of 52 deaths for now.  These deaths are not simply associated with unintended acceleration in Toyotas, they are attributed to them.

These are two very different things!  If Dr Mercola wants to compare 52 deaths attributed to defective Toyotas, he needs to compare it to zero deaths attributed to Gardasil, not 49.  On the other hand, if he wants his analogy to use the 49 deaths associated with Gardasil, he needs to figure out how many people have died from any cause within a year or so of riding in a Toyota.  Methinks the number will be slightly higher than 52.

Not to mention that he completely ignores the starkly different risk/benefit ratios of using Gardasil and driving a Toyota.  No one risks developing cancer or dying from not driving a Toyota.

He concludes:

There has been no recall for Gardasil, however. In fact, it is required for sixth-grade girls in D.C., Maryland, Virginia, and many other states. Merck denies any of the deaths are related to its vaccine — and of course, it is difficult for the grieving parents to prove they were.

No, Merck doesn’t deny the deaths are related to the vaccine, the data does.  There has been no recall of Gardasil because no recall is warranted, and in the meantime the vaccine is protecting millions from contracting HPV and the cancers it can cause.

My heart goes out to the grieving families to whom Dr Mercola refers; their loss is tragic regardless of its cause.  But their grief is being needlessly compounded, and the memory of those lost insulted, as Dr Mercola insists on misrepresenting the conditions of their deaths and callously exploits their loss to spread misinformation and fear of vaccination.

In spite of what the entertainment industry would have you believe, it is extremely difficult to save the life of someone in cardiac arrest.  A few random breaths, slow rocking chest compressions, even the ever-so-dramatic overhand blow to the chest accompanied by the scream “Don’t you die on me, dammit!” are unlikely to successfully resuscitate someone following an arrest, and even if it does, they won’t be in any shape to go chase Locke across the island with Jack and Kate five minutes later.

Even with properly performed CPR, started within seconds of an arrest, in a hospital with all the required expertise and support equipment, only roughly half survive their initial arrest event.  Even fewer (25-33%) survive to discharge from the hospital, and ~75% have a good neurologic outcome.  For arrests out of the hospital, where there can be huge delays in treatment, mere survival is significantly lower, often measured in the single digits.

The Limitations Of CPR

Why doesn’t CPR save more people?  Well, it really isn’t meant to; at least, not on its own.  Cardio-respiratory arrest is the common pathway of death, but it isn’t in itself a diagnosis.  The essential question to be answered is why someone stopped breathing, or why their heart stopped in the first place.  Unless you can answer that question and address the problem, even if CPR manages to restore a heartbeat it’s likely to stop again in short order.

It’s clearly unrealistic though to expect a random bystander to diagnose and treat another random stranger who happened to arrest in their vicinity.  The rescue breaths and chest compressions of CPR are therefore primarily designed to buy time, hopefully enough time to get to the EMTs and Emergency/Critical Care team whose job it is to figure out what caused the arrest in the first place and reverse it before permanent damage is done.

In spite of the availability of public CPR training courses and the widespread knowledge of the existence of CPR, most people remain untrained, and the vast majority of those who have been trained (even medical personnel) rarely have cause to think about the skill, much less practice it.  The result is that complete novices in CPR are the first responders to the overwhelming majority of arrests.  Should we be surprised, then, that in no more than half of all arrests is any CPR provided by bystanders, and that the quality of CPR when it is given is often sub-par?

I don’t mean that as an indictment of innocent bystanders of an arrest.  Simply witnessing an arrest is traumatic enough; to be in such a situation and asked to recognize the emergency, remember distant and somewhat arcane training, to have the initiative and courage to step forward and act, and to do so quickly and effectively is an immense amount to expect from anyone.  Nevertheless, if the goal is to reduce the amount of time a victim of an arrest is without circulation, we needed to find some way to enable more people to provide quality CPR.

K.I.S.S.

The desire to reduce these impediments to good CPR delivery, combined with improved understanding of the physiology of people during arrests and CPR, led the American Heart Association (AHA) to make some significant revisions to its CPR guidelines in 2005.  The revised guidelines were notably more streamlined, focusing less on tools, drugs, and advanced skills used by professionals, and even reducing the emphasis of breathing to focus instead on simply maintaining circulation of blood.  Instead of a variety of age stratified ratios of compressions to rescue breaths, the AHA began to teach a single universal guideline for single bystander CPR: 30 compressions at a rate of 100/minute, then 2 breaths, then repeat until either help arrives or the person is breathing on their own.  Compared to the prior CPR guidelines, it was simpler, easier to remember, and easier to execute.

In 2008 this was simplified even further.  For adult cardiac arrests, it was demonstrated that “compression-only” or “hands-only” CPR was equally effective to CPR using both compressions and rescue breathing, yet was simpler, even easier to remember, had fewer interruptions, and eliminated the aversion to mouth-to-mouth that some people experience.  All of this is thought to make people more likely to intervene and provide quality CPR, improving the odds of a dire situation.

Though it may seem counterintuitive not to provide rescue breaths for someone in cardio-respiratory arrest, the rationale is solid.  “Deoxygenated” or venous blood still has a good amount of oxygen in it (usually about 75% of oxygenated blood), and it carries a lot more than just oxygen.  The blood content of the nutrients that cells require is largely the same no matter whether the blood has been oxygenated or not, and blood flow also removes harmful metabolic byproducts that build up rapidly in its absence.  Though breathing is necessary in the long run, but you can get by without breathing a lot longer than you can survive without blood flow.

Studies have confirmed that “compression-only” and conventional CPR are equally efficacious in adult cardiac arrests, and that the “compression-only” method is easier to learn and remember.  By reducing the complexity of CPR to something that essentially fits on a bumper sticker, we are likely to improve the overall odds for adults who arrest out of the hospital.

…But Maybe Not That Simple

Have we made it too simple though?  Children arrest too, but for very different reasons than adults.  Most kids suffer respiratory arrests that then cause cardiac arrest, not primary cardiac arrests like most adults.  Eliminating rescue breathing from childhood resuscitations could in fact result in worse outcomes.  The AHA and medical community at large are aware of this, which is why the “compressions-only” CPR has not been recommended for children.  Even so, it is likely that in advocating for “compression-only” CPR to benefit adults, some children will inadvertently be subjected to sub-optimal CPR.

A new study out of Japan and published last month in The Lancet provides some sobering but powerful information that may guide future CPR guidelines.  The investigators examined all arrests of children over a 3-year span in Japan, documenting the type of arrest, presence and type of CPR, and short and long-term outcomes among other measures.

Out of 5158 childhood arrests, 2719 (53%) had no CPR attempted by anyone prior to EMS arrival.  Survival rates were abysmally poor without CPR at ~7% alive one month after arrest.  Though still depressingly low, CPR significantly improved survival to ~11%.  Of equal importance, those above 1 year of age who did get CPR, any type of CPR, also had markedly better odds of having favorable neurologic function at one month from the arrest.  As with the adult experience, an arrest out of the hospital is a dire situation, but any type of CPR is better than nothing, and can have a marked improvement in the (unfortunately small) likelihood of having a positive outcome.

The concern I had, however, was whether inappropriate “compression-only” CPR was inferior to conventional CPR with both compressions and rescue breaths, and whether we need to keep this in mind when designing our CPR program for the public.  The authors of this study were able to make just such a comparison.  Both forms of CPR were equally effective when the arrest had a cardiac origin, just as we’ve seen in adults.  However, as suspected, victims of arrests of a non-cardiac origin provided “compressions-only” CPR did no better than those given no CPR; only the combination of compressions and rescue breathing affected a significant benefit.

Furthermore, of the 2,439 children who did receive CPR, 36% received “compression-only” CPR.  Since 71% of all of the arrests in this study were non-cardiac in origin, this means that 25% of the CPR administered was inappropriate and ineffective.

Clearly, this study has limitations in being observational in design, and there are obvious issues generalizing from the Japanese population to that of the US, among other smaller concerns.  Nevertheless, this study provides a few important lessons to be considered.

First, it shines the harsh light of reality on the overly optimistic expectations of CPR sometimes provided but the news media and frequently by the entertainment industry.

Second, it demonstrates the efficacy of CPR in improving both survival and the quality of outcomes from out of hospital arrests, and the potential benefits of further enabling the public to perform appropriate CPR.

Third, it reinforces the decision of the AHA to restrict “compression-only” CPR to adults with suspected cardiac arrest, and not to apply it to children.

Finally, it seems to validate my concern that the introduction of “compression-only” CPR may be detrimental to the pediatric population.  Recall that the two CPR techniques were equally efficacious in adults (and apparently children) with an arrest of cardiac origin.  The AHA has therefore assumed that there was no detriment to the further simplification of the CPR guidelines, while yeilding a theoretical benefit derived from better quality of compressions and a greater percentage of bystanders willing and able to provide CPR.  If, however, “compression-only” CPR is only equal to conventional CPR in the adult population yet generates a negative impact on the quality of CPR provided to children, the AHA may choose to reconsider the wisdom of advocating “compression-only” CPR.  Obviously, this is still an open question, and further studies are needed (and are currently being performed), but I am curious how this information may affect the new guidelines due for release late 2010.

We will continue to refine the CPR guidelines to improve the outcomes from out of hospital arrests using the best available science, but the largest area for improvement is in the number of people in the community trained and willing to perform basic CPR.  It’s cheap, it’s easy, and the classes are actually fun.  Though you will hopefully never use the skill, you have the ability to help save a life.  Please, if you are at all inclined, get CPR certified.

As we have systematically removed the leading infectious killers of children from prominence, other organisms have naturally risen to the top of the list.  This has lead some to the fatalistic (and mistaken) conclusion that we are simply opening up niches to be inevitably filled by other virulent organisms.  This assumes that there is some mandated quota of say, meningitis, that children must suffer every year, and if one organism doesn’t meet this quota then another will fill it.  Were this the case, after vaccination we’d expect to see a shift in the causes of meningitis, but at best a transient drop in the total number of cases per year as other bugs step in to pick up the slack of their fallen, virulent, meningitis-inducing brethren.  Such is not the case.

Though new organisms are now the leading causes of invasive bacterial infections in children, and we have indeed seen some increases in non-vaccine targeted strains, as I’ll discuss below, the total number of such infections has dropped precipitously.  It’s fair to say that the vaccination program has done a remarkable job improving a child’s chance of surviving to adulthood in good health.  However, no one in their right mind would argue that the current state of affairs, as good as it is, is good enough, and so we have shifted our sights to the current leading cause of invasive bacterial infections in children, Streptococcus pneumoniae (S. pneumo, or pneumococcus).

The Need for a Pneumococcal Vaccine

S. pneumo is a challenging bug to prevent and treat.  Its 90 different serotypes together cause a variety of infections, from the relatively mild such as otitis media (ear infection) and sinusitis, to the far more serious including pneumonia, sepsis, meningitis, and osteomyelitis. Much of this versatility and the primary factor determining each strain’s virulence comes from the polysaccharide capsule surrounding S. pneumo.  This gel-like substance hides many of its antigens from exposure, and is itself a poor target for the immune system.

Increasing antibiotic resistance in some strains of S. pneumo certainly doesn’t help the matter, but neither is it the primary cause of S. pneumo’s current position of infamy.  The majority of strains are susceptible to good old penicillin, and even resistant strains are susceptible to other classes of drugs.  The problem is that in a small minority of cases the infection spreads so aggressively that children die or suffer complications in spite of rapid medical care and appropriate antibiotics.

This is why in children prior to 2000, and in spite of modern medical care, S. pneumo caused around 13,000 cases of bacteremia, 2500 cases of pneumonia, 700 cases of meningitis, and 200 deaths (not to mention 5,000,000 cases of otitis media).  As always, prevention would be better than treatment, and in 2000 the first vaccine against S. pneumo for children under the age of 2 was licensed in the US (an earlier vaccine, PCV-23, existed for adults but was incapable of generating a good response in children).  PCV-7 (Prevnar) targeted only 7 of the more than 80 known serotypes, but the seven were well selected, accounting for 80-85% of the cases of invasive disease and a majority of penicillin resistant strains.

Coverage Gaps and Moving Targets

The subsequent 10 years have been almost exactly what you would hope for from the vaccine.  Invasive pneumococcal disease in children has dropped by 76% (including non-targeted serotypes), and disease from targeted serotypes, which recall made up 80% of all invasive disease before the vaccine, dropped 99%.   We’ve even seen a modest but significant decrease in the incidence of S. pneumo disease in the elderly, which is most consistent with the effect of herd immunity.  This is an outstanding success.

Though PCV-7 is effective, it’s also far from perfect.  Predictably, the strains not targeted by PCV-7 have persisted in the population and become more common.  Some of these strains are less pathogenic, but a few have shown themselves capable of virulence, and so in the last decade we’ve seen a shift in the behavior of infections caused by S. pneumo.  One such example of this may be seen in the increased rate of empyema.

Occasionally during a pneumonia bacteria can also infect the space between the lung and the wall of the chest, causing an accumulation of pus that is difficult to treat with antibiotics alone, and usually requires some form of drainage. Typically this is done with a tube inserted between the ribs or thorascopic surgery, and usually includes a prolonged hospital stay.  Needless to say, an empyema is undesirable, and the rate of this complication from pneumonia seems to be increasing.

This concerning trend has been most recently demonstrated by an article appearing in Pediatrics.  Between 1997 (3 years pre-PCV-7 licensure) 2006, the authors found an approximate 50% drop in invasive pneumococcal disease in general, pneumonia, meningitis, and bacteremia, consistent with the existing literature confirming the general efficacy of PCV-7.  However, they also were able to demonstrate a subtle increase in the rates if empyema during the same amount of time.  This means that with a near halving in the total number of pneumonias, but an increase in a complication of pneumonia, the risk of developing an empyema during a pneumococcal pneumonia has roughly doubled in the last decade.

Now comes the hard part: Why?  Well, frankly, we don’t yet know.  This study doesn’t establish the causative mechanism behind the increased incidence of empyema; it simply establishes that it has increased in spite of pneumococcal vaccination. The increase could be part of a previously occurring trend, after all, the incidence of empyema was already increasing before the vaccination was implemented.  It could be from a shift toward serotypes that are more prone to cause empyema, but aren’t targeted by the vaccine.  Unfortunately this particular study isn’t designed to look at involved serotypes, and the other literature to support this hypothesis is currently mixed.  I find it compelling to note that this very study also demonstrates a nearly identical increase in the rate of empyema associated with Staphylococcal pneumonia, suggesting an unidentified common factor between the two.

We Can Do Better

We know that PCV-7 is effective at controlling most infections from targeted serotypes, that non-targeted serotypes are beginning to thrive, and the increased rate of empyema has not been curtailed by the current vaccine.  The next logical step is to broaden our coverage to include the non-targeted pathologic strains within the vaccine.

This is precisely what has been done.  Several vaccines with a broader scope have been in development, and on February 24th the FDA licensed the first of this next generation of pneumococcal vaccines. PCV-13 targets all seven prior serotypes and includes an additional six that together comprise the most common and pathological serotypes currently in circulation (serotypes 1, 3, 4, 5, 6A and B, 7F, 9V, 14, 18C, 19A, 19F, and 23F).  It is slated to replace the current PCV-7, will follow the same 4-shot 2, 4, 6, and 12-15 month schedule, and can be used to complete a series of PCV-7 vaccinations.

This vaccine, like every other one, has undergone extensive testing for both safety and efficacy.  It is built on the identical technology as PCV-7 that has a decade’s worth of excellent safety, and will, as with all other vaccines, undergo even more rigorous post-release surveillance.

Based on PCV-7’s success, we have every reason to expect an even greater reduction in the burden of serious infections suffered by our children. If we’re lucky, we’ll soon have to declare a new bug the leading cause of invasive bacterial infections in children, not because of its success, but because of S. pneumo’s fall.

Herd immunity is a fascinating effect, and one of the mainstays of a public vaccination effort.  The idea is that if enough people in the community are immune to a particular disease, then those who are susceptible will rarely come into contact with a person who is contagious, and the disease will be unable (or find it difficult) to spread.  This results in a greatly reduced risk of infection for the entire population regardless of their individual immunity.

This has lead to the belief that because of the protection of the herd’s immunity, individuals now have the option to avoid even the minimal cost and risk of vaccination while having the same reduced risk of infection as if they had vaccinated.

Let’s set aside the fact that that there are people who have no choice but to rely upon herd immunity as their sole line of protection against these infections.  Forget that there is a threshold below which herd immunity collapses, and that our current vaccination rates tend to be right on the cusp of that threshold.  Pay no attention to the fact that the personal decision to not vaccinate deprives others of their sole protection from these infections.  Finally, ignore the ethics and self-defeating nature of benefiting from the sacrifice of others while simultaneously eroding the efficacy of the herd immunity being exploited.  On a small enough scale, doesn’t the tactic of hiding in the herd provide the same protection as getting vaccinated without incurring the minimal risk of vaccination?

Not so much.

Countless reports of outbreaks around the world consistently describe a disproportionate number of infections during vaccine-preventable outbreaks occurring in the unvaccinated.  For instance, in Indiana in 2005 an outbreak of measles infecting 34 people was traced to a 17-year-old unvaccinated girl who had contracted measles in Romania.  In that outbreak 94% of the infected were unvaccinated.

This scenario was repeated during a measles outbreak in California in 2008 where 12 children were infected.  The index case, an unvaccinated boy who had traveled to Europe, infected both of his siblings, five schoolmates, and four children from his pediatrician’s office.  None of the children were vaccinated, though three of the four infected in the office were too young to have been vaccinated.  Zero vaccinated children contracted measles.

Reports such as these highlight how quickly these diseases can spread, how easily the unvaccinated are infected, and the limited effectiveness of voluntary isolation.  They also demonstrate the effectiveness of herd immunity in containing the infection, and rather strongly suggest that, even with intact herd immunity, the vaccinated and unvaccinated are not at equal risk of infection.

How much greater is the risk, though?  10%?  50%?  Perhaps fully twice as likely to be infected?  The magnitude matters to parents (and physicians) who are weighing the risks of vaccines and their corresponding diseases.

A group from Kaiser Permanente of Colorado has attempted to help put a number on that increased risk.  Within the last year they have provided two matched case-control studies that quantify the magnitude of the risk children incur because of vaccine refusal.

Their first study found that the act of refusing to vaccinate against pertussis (whooping cough) placed children at a 23 times greater risk of contracting pertussis.  That’s a 23 fold-increased risk of a disease that, in children under 12 months of age from 2000-2004 in the US caused 62.8% to require hospitalization, 55.8% to have apnea, pneumonia in 12.7%, and death in 0.8%.

Their second study, published just this month and following the same format as the first, focused instead on the risk of varicella (chickenpox) infection after vaccine refusal.  Here they identified an 8.6-fold increased risk of infection with a disease that as recently as 1995 (when the vaccine was released), tallied 3,000,000 infections, 10,000 hospitalizations, 4,000 cases of pneumonia, 600 cases of encephalitis and 100 deaths per year.

These findings further reinforce the fact that even in a community with intact herd immunity, the choice to remain unvaccinated places children at a markedly higher risk than their vaccinated counterparts.  The delusion that hiding children within the herd provides them with protection even remotely equal to vaccination must be abandoned.

It bears to be stated again, frankly and clearly.  The choice to refuse a vaccine, to “hide in the herd,” is an active decision to accept a markedly higher risk of infection, its complications, the associated medical costs and lost wages, the responsibility of spreading the disease to others should an infection occur, and to choose to undermine the very herd immunity on which we all depend.

Parents want to be fully informed about the medical decisions they make for their children, and rightfully so.  To that end, we do everyone a disservice by allowing the public discussion to be dominated by the risks of vaccines to the exclusion of other equally important topics, including the risks of not vaccinating.  Studies such as these are a needed and welcome addition to the literature, and should provide a valuable insight for people wanting to make a properly informed decision.

The NYT article is primarily an anecdote of a friend of the author who suffered from severe asthma, but who had improved since he began using the BBT.  The author briefly discusses asthma, the history and theory behind Buteyko and hyperventilation before wrapping up with an attempt to provide evidence to support the legitimacy of the story.  The friend’s pulmonologist is quoted to confirm that “based on objective data, his breathing has improved…”  She cites controlled clinical trials “in Australia and elsewhere” where patients have reduced their use of medications, including a purported British study of 384 patients where patients had a 90% reduction in rescue inhaler use and 50% reduction in steroids.  She ends by pointing out that the British Thoracic Society has given BBT a “B” rating, and an admonition to “the pharmaceutically supported American medical community to explore this nondrug technique.”

Never having heard of BBT before, the NYT article left me with several questions.  Who was Buteyko?  How did he develop the BBT?  What is BBT, what does it claim to do, and how does it claim to work?  Is the evidence as presented in the NYT article accurate? And finally, what evidence exists within the literature that BBT is an effective treatment for asthma?

Who was Konstantin Buteyko?

Given the relative obscurity of BBT in the US and in modern medicine in general, I am using the sites of Buteyko’s primary presence in the US, the Buteyko Center, and the Buteyko Institute of Breathing and Health as my primary sources of its theory and history.

Buteyko’s story is proudly presented in great length (but frequently lacking in critical detail) on the Buteyko Center website.  I encourage you to read it in its entirety for full effect, for it is fascinating and bears a striking similarity to that of the other founding figures of alt med belief systems (D.D. Palmer, Hulda Clarke, Mikao Usui, Samuel Hahnemann). What follows are the high points from a full bio on Buteyko by Sasha Yakovlev-Fredrickson, a Buteyko Specialist at the Buteyko Center USA.

Born in 1923 in the Ukraine, he trained as a mechanic until World War II, where he served in the Soviet military on the Eastern Front and became fascinated by the injuries he witnessed.  After the war ended he joined the First Medical Institute in Moscow and began his medical training.

Somehow, while still a medical student he is said to have specialized in hypertension.  Around the same time and while still in his 20’s, he is diagnosed with “a severe and lethal form” of hypertension that left him with months to live in 1952.  We are given no more detail, and the story is already bordering on medical incoherence.

His discovery apparently came in a moment of insight, or perhaps revelation.  One night in 1952, as he stood alone staring out at the night sky and contemplating his illness, he was dazzled by a bright light, and that “in the midst of his impending demise” he noticed that he was breathing heavily as was struck with the revelation that the heavy breathing he was experiencing was not a symptom, but the cause of his problems.  He intentionally slowed his breathing, and as he did so, he felt immediately better.  Following this revelation we are told that he went around the hospital telling people to breathe more slowly and that they immediately felt better as well.  Based on these experiences he created the Buteyko Breathing Technique.

It might be that he stumbled in this moment onto an immensely powerful and hitherto unknown insight into human pathophysiology.  On the other hand, there may a more simple explanation. We have in Buteyko a young man recently returned from the battle lines of WW II, suffering from hypertension (extremely uncommon in a young man), who is experiencing hyperventilation, flashing lights, and an apparent feeling of impending doom.  One would be hard pressed to find a better setup for and description of a panic attack.  Slow, controlled breathing that Buteyko described using can not only resolve the acute symptoms of a panic attack, but can also return a sense of control to the person afflicted, reducing their anxiety, and potentially alleviating hypertension.  Panic attack or stroke of stunning inspiration; Occam’s razor might have something to say on the matter.

Nevertheless, smitten with his new theory and armed with his very personal n=1, Buteyko began to treat patients.  The subsequent decades of his life are full of stories of persecution and suppression, physical intimidation and destruction of his laboratory, professional sabotage and fears of incarceration.  Undaunted, Buteyko continued using and promoting his therapy, and supposedly discovered that BBT could cure at least 150 different diseases and disorders!  Buteyko compared himself to Dr Semmelweis, and the power of his technique to atomic energy.  In 1987, having obtained a “top secret” patent on BBT from the Soviet government, he established the Buteyko clinic.

Never one to rest on his laurels, Buteyko continued to explore the power of BBT.  He is said to have hardly slept, and to have lived without food for 50 days at a time.  It is further claimed that he became an advanced spiritual practitioner with the ability to read people’s thoughts, predict the future, and at one point declared that civilization would die if we didn’t stop hyperventilating.

I’ll let these claims stand on their own without further comment, other than to reflect on the reliability of the mind that makes such statements.

What is Buteyko Breathing Therapy?

Eccentricity of the eponymous inventor of BBT aside, what can we say about the therapy itself?

How Buteyko researched and practiced his treatment from his revelation in 1952 until the establishment of his clinic in 1987 is obscure at best.  Per the history given on the Buteyko Center site, at the same time that he is enduring professional ridicule and sabotage and hiding his practice from the government for fear of imprisonment, he is also able to treat enough people to discern over 150 different uses for BBT and be offered (and then refuse) a job with the Russian Space Agency.  Despite what one would expect to be a wealth of data to support claims of efficacy for so many different conditions, Buteyko himself never published a single paper, and not until 1995 does any reference to his name appear in the medical literature.

Even according to the history provided by the Buteyko Center, not until 1981, nearly 30 years after Buteyko’s revelation/discovery was a second trial conducted regarding BBT’s efficacy; it is never peer reviewed or published.  The same source then tells that soon after acquiring his “top secret” patent for BBT, in 1985 the Soviet Public Health Ministry issued a recommendation that all medical professionals treat patients with his method.  After establishing his clinic in 1987 he treated people with asthma, allergies, hypertension, kidney problems, cardiac problems, gastrological problems, immune deficiency, cancer, and even victims of Chernobyl and AIDS patients.

The list of diseases treated by BBT didn’t end there.  On the Buteyko site you can peruse the list of 150 curable diseases and conditions Buteyko believed he could treat.

But what is BBT?  How can one therapy treat the varied legion of diseases on that list?  Again, I’ll let the Buteyko Center and the BIBH speak for themselves on the matter here and here.

As you can see if you follow the links, there is a lot of talk about hyperventilation, but they are rather sparse on the details.  If you want the details, break out your wallet.  The Buteyko Center and BIBH are willing to start doling out details in exchange for the digits on you credit card.

What of BBT’s Physiologic Plausibility?

So BBT’s origins are highly dubious, but what of its plausibility?

Let’s examine the physiologic explanation provided by the Buteyko Center for why it cures not only asthma, but all of the myriad conditions listed on their site.  They are kind enough to have Ira Packman, M.D. provide an explanation for doctors derived from that of Buteyko himself that can be found here.  (Buteyko’s is here.)

The explanation can be distilled down to this:

-When people hyperventilate, their arterial CO2 drops, making their blood alkaline.

-An alkaline pH increases hemoglobin’s affinity for oxygen.

-If hemoglobin holds onto oxygen more tightly, it won’t release as much to tissues.

-Less oxygen released by hemoglobin will cause hypoxic damage to tissues.

-Kidneys will try to correct the alkalosis by eliminating bicarbonate.

-Along with bicarbonate loss phosphorus and magnesium will be lost.

-Hypophosphatemia will compromise the creation of ATP.

-A lack of ATP will impair the function of afflicted tissues.

-A low level of CO2 can cause vasospasm and further reduce the blood supply to tissues.

Ignore the gross oversimplifications and important omissions in the explanation for the moment and take it at face value.  These are all testable hypotheses.  If Buteyko is correct, and chronic hyperventilation is the cause of all (or any) of the diseases listed on their site, then one would expect to see a high pH, low CO2, low bicarbonate, low phosphorus, low magnesium, and signs of anaerobic metabolism such as a low mixed venous O2 saturation or elevated serum lactate level.

These are extremely common labs that physicians (especially ICU physicians such as myself) are intimately familiar with.  According to Buteyko, this lab pattern should be a nearly universal feature of all disorders cured by BBT.  Guess how many actually routinely display anything remotely resembling it.

None.

This hypothesis also predicts that an asthmatic who begins to retain CO2 should have both their symptoms and pathophysiology improve.  In truth, elevation of CO2 in a symptomatic asthmatic is one of the more ominous signs in critical care medicine, and is the harbinger of respiratory failure and death.

What about the omissions and inaccuracies? First, the mechanisms Buteyko and Packman discuss to maintain blood pH are highly efficient, and are capable of correcting dramatic derangements in pH over the span of hours to days.  This is superbly demonstrated by chronic hypoventilation, where for a variety of reasons people retain carbon dioxide and yet have a normal pH.  With a normal pH the Bohr effect is neutralized.

Second, even if the Bohr effect remained in play, it is a minor determinant of oxygen delivery, easily compensated for by numerous other mechanisms, and insufficient to independently cause hypoxic injury or dysfunction.

Third, Packman says there is an “over excretion of bicarbonate.”  Even within his flawed concept of physiology, loss of bicarbonate would be an appropriate response to balance the blood’s pH, and the kidney will not overcompensate, therefore the term “over excretion” is inappropriate and implies a nonexistent pathology.

Fourth, the electrolyte interactions described by Packman are very confused.  The electrolytes most closely tied to the kidney’s bicarbonate management are sodium and chloride, not magnesium and phosphate.  Phosphorus does play a smaller role in the buffering capacity of the kidney, but contrary to Packman’s claim that a state of alkalosis will result in loss of phosphate, it is in fact when excessive hydrogen ions are secreted during a state of acidosis that phosphate is lost in the form of H₂PO₄^-.  It is true that hypophosphatemia can induce loss of bicarbonate through the actions of parathyroid hormone, but the inverse, that loss of bicarbonate induces phosphate loss, is not true.

Finally, though extreme hypophosphatemia can indeed compromise the body’s ability to create ATP, the resulting energy failure will cause a metabolic crisis which will not only be clinically and biochemically apparent, but which will cause the exact opposite pH-based effects upon which Buteyko’s hypothesis depends.

Now the lack of physiologic plausibility does not in and of itself mean that Buteyko method is ineffective.  What it does mean is that the physiologic explanation for its mechanism is likely dramatically wrong, and that the primary proponents of the technique have not only failed to recognize this fact, but have ignored elementary flaws in their hypothesis apparent in both theory and practice.

Buteyko Breathing Therapy and the Literature – Not Burdened by an Overabundance of Evidence

Buteyko and his devotees have made some remarkable claims while providing almost no evidence; an unrestricted Pubmed search of “Buteyko” yields a grand total of 21 hits.  But 21 is (slightly) more than zero, so let’s look at the published literature.  Virtually all of these 21 Pubmed hits discuss the use of BBT for asthma, as was indicated in the NYT article that triggered this post.  There are no published studies evaluating BBT for any of the other 149 diseases Buteyko claimed to cure.

The following are the sum total of published clinical trials regarding BBT’s use without regard to quality, design, size, bias, or result:

1) Buteyko breathing techniques in asthma: a blinded randomized controlled trial. Bowler SD et al. Med J Aust 1998:  39 subjects. Significant reduction in use of both chronic and rescue inhalers, but no change in lung function tests (PEF or FEV1) or end tidal CO2.

2) Effect of two breathing exercises (Buteyko and pranayama) in asthma: a randomized controlled trial. Cooper S. et al. Thorax 2003. 90 subjects enrolled, 69 completed the study.  Improved symptoms and reduced bronchodilator use with BBT, but no change in lung function tests (FEV1), number of exacerbations or amount of steroids used.

3) Buteyko Breathing Technique for asthma: an effective intervention. McHugh P et al. N Z Med J. 2003. McHugh: 38 subjects. 50% reduction in steroids and 85% reduction in rescue inhaler use at 6 months in BBT compared to no change in steroid use and 37% reduction in rescue inhalers in the control group, but no change in pulmonary function tests (FEV1).

4) A clinical trial of the Buteyko Breathing Technique in asthma as taught by a video. Opat AJ et al. J Asthma 2000. Opat: 36 subjects.  Participants viewed a video of BBT or a placebo video twice daily for 4 weeks.  Modest improvement in quality of life and a reduction in bronchodilator use, but no improvement in pulmonary function tests.

5) A randomized controlled trial of the Buteyko technique as an adjunct to conventional management of asthma. Cowie RL et al. Respir Med. 2008.  129 subjects.  Significant reduction in the amount of steroid used in BBT group, but no difference in asthma control between the two groups.

6) Effect of mouth taping at night on asthma control – a randomized single-blind crossover study. Cooper S. Respir Med. 2009.  51 subjects.  No difference in pulmonary function tests or symptom scores resulted from forced nasal breathing overnight.

7) Investigating the claims of Konstantin Buteyko, M.D., Ph.D.: the relationship of breath holding time to end tidal CO2 and other proposed measures of dysfunctional breathing. Courtney R et al. J Altern Complement Med. 2008.  83 subjects.  Breath Holding Time as defined by Buteyko was found to have the exact opposite correlation with alveolar CO2 that his theories predicted it would have.

8 ) The effects of carbon dioxide on exercise-induced asthma: an unlikely explanation for the effects of Buteyko breathing training. Al-Delaimy WK et al. Med J Aust. 2001. 10 subjects.  Patients were supplemented with CO2 to test Buteyko’s hypothesis that a higher CO2 would result in a reduction in asthma symptoms. Breathing 3% CO2 did not prevent exercise-induced asthma.

Notably absent from this list is the British study containing 384 patients touted and linked to in the NYT article.  As it turns out, that was not a peer-reviewed study, but instead only an abstract at the 2003 British Thoracic Society Winter Meeting.  In spite of its remarkable results, it has not in the following 6 years been published in a peer-reviewed journal.  It is, for all intents and purposes, a non-study.

The three studies designed to test Buteyko’s proposed mechanisms of action (6, 7, and 8 ) do not support Buteyko’s theories, and are in keeping with my earlier analysis of its plausibility.

The five studies comparing BBT to a control for treatment of asthma (1-5) show a variable though reasonably consistent reduction in both rescue and maintenance drug use.  Even more consistent however is the utter lack of any change in the participant’s pulmonary function tests.

Given the most charitable interpretation and taken at face value, these studies imply that BBT can alter a patient’s perception of their symptoms, and perhaps prevent overuse of asthma medications.  However, they also provide evidence that BBT does very little to alter the underlying pathophysiology of asthma, and absolutely no evidence to support Buteyko’s claim that BBT can cure asthma.

Buteyko Breathing Therapy and Asthma – A Broken Clock is Still Right Two Seconds Per Day

Taken as a whole, this reading of the literature is in keeping with the British Thoracic Society’s Guidelines, which state:

The Buteyko breathing technique specifically focuses on control of hyperventilation and any ensuing hypocapnia. Four clinical trials suggest benefits in terms of reduced symptoms and bronchodilator usage but no effect on lung function.  Buteyko breathing technique may be considered to help patients to control the symptoms of asthma.  Grade B”

Though I think that the BTS authors were overly generous in ranking the four evaluated articles as 1+ level of evidence (meaning a well conducted meta-analysis, systematic review, or RCTs with a low risk of bias), their conclusions are not unreasonable within the framework of Evidence Based Medicine.

Of course, as I consider this small set of literature from the perspective of Science Based Medicine, I’m reminded of John Ioannidis’ essay “Why Most Published Research Findings Are False.”

…a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance.”

These studies can be found wanting on nearly every point outlined by Ioannidis. Already weak when viewed through the lens of Evidence Based Medicine, through that of Science Based Medicine the Buteyko literature looses much of its remaining impact.

SUMMARY

Buteyko reminds me in many ways of D.D. Palmer.  Starting from an erroneous observation, using flawed logic, lacking prior plausibility, forsaking scientific validation, and promoting their techniques as virtual panaceas, they each nevertheless may have found small medical niches where their techniques may have some limited utility.  Palmer’s niche appears to be treatment of low-back pain, and for Buteyko, it may be the symptomatic relief of mild asthma symptoms.

If however, you are looking for the Buteyko Breathing Technique to cure your asthma, I wouldn’t hold my breath.

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.

I am just a parent with some questions about vaccine safety and was happy to find your website.  I have noticed that the Scandinavian countries do not routinely recommend HepB vaccination unless the mother is a known carrier.  I did not see this addressed anywhere on your website and I hope you or one of your colleagues might consider discussing the reasons that some advanced countries are not routinely giving this particular vaccine. Thank you.”

Vaccination is a complicated and at times confusing topic that generates a large number of quite reasonable questions by parents like the one above.  At the same time, the ever-wandering aim of the anti-vaccinationist movement appears once again to be falling on the vaccine against Hepatitis B, and I’ve heard them pose this very question with the intent of sowing doubt in the current vaccination schedule.  Regardless of the source, this question is clearly on the mind of some parents, and I am happy to answer it.

As usual, this question has quite a bit to parse out.  I think it may be most helpful to examine why we vaccinate against Hepatitis B the way we do in the US, how most countries in the world approach the problem, and finally examine the reason why eight European countries do not universally vaccinate against HBV.  First things first though: what is Hepatitis B?

HEPATITIS B

Hepatitis B (HBV) is a double stranded DNA virus found in the bodily fluids of infected people including their blood, semen, and saliva, and can be transmitted through sexual contact, exposure of infected fluid to mucous membranes, or through injection.

As the name suggests, infection causes damage primarily to the liver, though the spectrum of disease experienced by any one person can be quite broad.  In adults, 50-70% of infections are asymptomatic or mild enough to not come to medical attention.  The remaining adults experience a range of hepatitis lasting weeks to months, with ~1% of these being a fulminant, life-threatening infection.  Adults are relatively efficient in their ability to clear the virus after the initial infection, and only ~10% become chronicly infected carriers.

Children, on the other hand, present a very different pattern of disease.  Though ~90% of infected children are initially asymptomatic, they are rarely able to clear the virus.  90% of infants and 25-50% of those 1-5 years old will become lifelong carriers.

Chronic Hepatitis B infection is a serious problem.  Beyond the ability of most chronic carriers to spread the virus throughout their lives, ~ 20% of people with chronic Hepatitis B develop cirrhosis, a condition where the liver cells are lost and the liver becomes progressively more fibrotic and dysfunctional.

Cirrhosis isn’t the only life-limiting problem to result directly from chronic Hepatitis B infection.  Hepatocellular carcinoma, a primary cancer of the liver, is in the top 10 cancers in both sexes in the US, and 60-80% of all cases are cause by Hepatitis B.  All told, around 25 % of people who become chronically infected with Hepatitis B will die from its complications.

Hepatitis B is a major cause of worldwide morbidity and mortality. More than 1/3 of the world’s population has been infected with Hepatitis B and 5% are chronic carriers.  That totals up to around 350,000,000 people chronically infected, and around 620,000 deaths from HBV yearly.

As in many health care related issues, the worldwide epidemiology of HBV infection does not necessarily reflect that of the United States.  Even so, the picture isn’t particularly pretty.  Around 5% of the US population has been infected with Hepatitis B, and 0.3 are chronic carriers.  Most HBV infections occur in those aged 25-44 (4/100,000), with the lowest rates of infection in those under 15 (0.1/100,000).   In 2007 4,519 new cases in the US were reported to the CDC, though this represents a fraction of the total number of infections.

These numbers are significant.  To put this in perspective, the mortality from HBV in the US was 5 times higher than Haemophilus influenza type B and 10 times greater than measles before vaccination was introduced.

The Hepatitis B Vaccine

HBV is a relatively stable virus posing a serious public health threat with humans as the only known reservoir, and as such is a prime target for prevention, and theoretically eradication, through vaccination. The first vaccine against HBV became available in 1981, and the current recombinant vaccine has been in use since 1986.  As a recombinant vaccine it contains proteins normally made by HBV, but does not have the virus itself, and therefore carries no risk of HBV infection.

As far as efficacy is concerned, the HBV vaccine has a very high response rate, inducing an appropriate antibody response in more than 95% of people from birth to 30 years of age, and decreasing but still significant response rates in older age groups.  Immunity from the vaccine lasts at least 20 years in healthy individuals.

The HBV vaccine has an excellent safety record.  The most common side effects are pain and swelling at the injection site in ~3% of people, and fever in ~1%.  The only serious confirmed reaction is anaphylaxis that occurs in 1/600,000 injections with no deaths reported in over 20 years of use.  Concerns regarding the HBV vaccine’s association with demyelinating diseases, the use of thimerosal in its formulation in the past or aluminum at the present have all been investigated and found to be without support; I will give such allegations no further time in this post.

Strategies of Hepatitis B Vaccine Use

There are a number of viable strategies available to countries seeking to address the spread of HBV in their populations, and variants on each.  When deciding which strategy is best for any given country, there are multiple factors to consider, including disease severity, the availability and efficacy of treatments, the risk and cost of infection, the risk, efficacy and cost of vaccination, etc.

The first option is to vaccinate people at high risk of infection.  In situations where the risk of infection is very low this makes good sense.  For instance, in the US the risk of contracting Yellow Fever is essentially zero at baseline without vaccination.  No risk or cost of vaccination, no matter how small, is small enough to offset zero risk of disease, therefore we do not routinely vaccinate against it.  However, if you were to travel to an area where Yellow Fever is endemic, your personal risk can suddenly become significant, and easily justify the minimal cost and risk of vaccinating you as a person at high risk.

Since the majority of people infected with HBV have identifiable risk factors, this approach makes some sense.  However, it has several major drawbacks.  It requires all individuals in a high-risk group to have health care, be identified, and to acquire the vaccine before they are infected.  This is labor and cost intensive, and extremely unlikely to capture the entire target population. Well executed, this approach can protect a majority of people at high risk, but in the case of HBV it will not immunize a large enough population to generate a herd immunity effect. The greatest flaw of this approach lies in the 1/3 of HBV infections that occur in people with zero known risk factors who, by definition, are unable to further reduce their risk, and are left unprotected by a vaccine. These shortcomings guarantee this strategy will fail to fully control the spread of HBV in the community.

The second approach is to vaccinate the entire population as they enter into the age of greatest incidence of infection, adolescence and early adulthood.  This addresses one of the shortcomings of the first strategy, namely the need to identify people at high risk.  It also takes advantage of the fact that children more reliably have health-maintenance office visits than do adults, and are more likely to be given vaccinations as part of a universal schedule.

Though this captures a large majority of the total number of infections, it too has a flaw; it fails to address the people infected in early childhood.  Though this is a relatively small number of people (4% of HBV infections), remember that children are far more likely to become lifelong carriers, and thus make up a disproportionate number of the infected at any one point in time (24% of chronic carriers).  While more effective at reducing the prevalence of HBV in the population than only vaccinating high-risk groups, this strategy too has little hope of eliminating HBV.

The third possible strategy is to vaccinate people at the time of birth.  This strategy addresses the problem of perinatal infection, prevents the acquisition of HBV by people during early childhood when the risk of chronic infection is highest, and since the immunity it induces lasts for decades it covers the entire population during the highest risk times of their lives.  Universal vaccination with HepB vaccine at birth, even in regions with a low prevalence of chronic carriers like the US, could reduce mortality by an additional 10-20% compared to early childhood vaccination.

Even this strategy has a drawback, however, and that is time.  Beginning an immunization program with only infants would take a few decades to generate a maximum reduction in HBV in the population.

The US Vaccination Strategy

Though the burden of disease from HBV in the US is relatively low compared to say, heart disease, it remains a significant public health threat only partially addressed through screening, education, and preventative measures, and with limited treatment options.  This makes it an ideal target for vaccination.

From 1981 through 1991 the US vaccinated only people with identified risk factors. Predictably, this campaign had an underwhelming effect on HBV infections seen during this time period.

In 1991, the strategy was reworked to better address the various methods of HBV transmission in an attempt to eliminate HBV spread in the US.  The new strategy is an amalgam of all three strategies described earlier. In addition to vaccination of high risk groups, we began universal vaccination of all infants at birth, vaccination of adolescents, and prenatal screening of pregnant women to identify children who would require not only vaccination at birth but also Hep B immunoglobulin (HBIG).

Since its launch in 1991, we have seen a steady decrease in Hepatitis B infections. Hep B incidence in the US fell from 10.7/100,000 in 1983 to 2.1 per 100,000 in 2004. (25,916 total cases down to 6212 cases).  Though it’s true other factors have been contributing to HBV’s decline, most notably the public education campaign aimed at curbing the spread of HIV, this doesn’t account for the pattern of HBV decline across age groups.  There has been a 95% drop in HBV in people under 15 years of age, 87% in ages 15-24, 71% from 25-44, and 51% decrease in people over 45 years old.  This is precisely what you would expect from a pediatric vaccination campaign.

Using a cost effective and exceptionally low-risk intervention of universal Hep B vaccination the US is well on its way to control, if not elimination, of HBV.

The Northern European Vaccination Strategy

The strategy taken by the US is typical of most developed nations, even those with a relatively low incidence of HBV.  In 1992 the WHO recommended the inclusion of HBV vaccination in nearly all national vaccination programs.  Since that time, the vast majority of countries (177/193 countries) have adopted infant HBV vaccination into their childhood schedules as can be seen here.  This graphic also illustrates the few countries that have instead opted to vaccinate only high-risk individuals, primarily those in Northern Europe, including Scandinavia.

The reason these countries have not adopted universal vaccination against HBV is the exceptionally low level of HBV in their population and the associated costs of prevention.  Sweden, for instance, has one of the lowest prevalences of HBV in the world at 0.05%.  This is 6 times lower than what we have in the US, with the majority of cases occurring in those engaged in high-risk activities or in immigrant populations that tend to have minimal contact with the indigenous population.  The public health organizations of these Northern European countries consider HBV to be a minor public health problem best addressed by targeted vaccination.  The cost of instituting universal vaccination would not offset the benefit of further reduction in HBV prevalence in their countries.

It is interesting to note that though these countries have low baseline rates of HBV infection, they have not generated the same relative decrease in rates that countries, like the US, have been able to produce with universal HBV vaccination.  This fact, in combination with high immigration rates to these countries from areas of heavy HBV, makes it likely that the cost/benefit ratios of the Northern European countries will sway even more strongly in favor of universal HBV vaccination over the next several years.

It is also worth noting that of the many factors being weighed by the medical community and public health officials of these Northern European nations, serious concerns of the Hepatitis B vaccine’s efficacy or safety are not among them.

Conclusion

We will continue to make progress in medicine by never being satisfied the care we provide is good enough; the ongoing debate about how best to apply the Hepatitis B vaccine is an excellent example of this concept.  The inconsistency between these nations’ vaccination policies is little more than physicians and health care officials seeking the most efficient and effective use of the vaccine within the unique conditions inside their borders.

In the first bit of good news, on October 14^th Simon Singh was granted permission to appeal the High Court ruling on meaning of the term “bogus” within his original article.  I’m sure most readers of this blog are familiar with Simon Singh’s legal battle with the British Chiropractic Association (BCA) regarding an article in The Guardian entitled “Beware the Spinal Trap.”  We’ve covered it several times over the last year and will continue to do so as the case progresses. The nuances of the British legal system (or any legal system for that matter) are beyond my ken, and are far better explained by Jack of Kent here.  The take-home point is that gaining permission to appeal the ruling on meaning was virtually essential if Simon were to have any real chance of winning this lawsuit.

Even if the BCA should win its lawsuit for libel against Singh, it seems likely to be something of a pyrrhic victory.  After all, in the year since this story began, we’ve been belatedly provided with the BCA’s best evidence in support of chiropractic’s efficacy, and promptly treated to its subsequent evisceration.

We’ve also been given insight into the standards held and practices recommended by the McTimoney Chiropractic Association (MCA), which by its own reckoning is the second largest chiropractic association in Europe.  In an apparent response to the attention brought by the BCA’s lawsuit, the MCA advised its members to take down their websites and remove all reference to treatment of “whiplash, colic, or other childhood problems” from their places of business to avoid a “witch hunt” targeting “any claims for treatment that cannot be substantiated with chiropractic research.” If only the Malleus Maleficarum had been written with such high standards of evidence!

In the same email we were treated to their unique perspective on ethics and the right of patients to information with this gem of a quote (punctuation intact):

we strongly suggest you do NOT discuss this with others, especially patients, Firstly it would not be ethical to burden patients with this…

I find this statement to be the most abhorrent in the entire MCA email.  This is advice from a major professional organization to withhold information from patients.  And not just an esoteric bit of chiropractic minutiae, but information that pertains to entire swaths of chiropractic practice.  Even worse, nowhere in the email does it advise MCA chiropractors to stop treating the stated conditions, just to obfuscate the fact that they do.  As I said, abhorrent.

So in their attempt to silence one critic through litigation, the BCA has drawn attention to the paucity of evidence supporting many of its practices, shown that its chosen response to criticism is litigation and not scientific discourse, and prompted some alarmingly unethical advisory statements from their chiropractic colleagues.  For a group supposedly striving to gain legitimacy within modern medicine, their current course of action seems to be ill conceived at best.  As the saying goes, “Those who live in glass houses shouldn’t throw stones.”

Simon has rightfully received an outstanding amount of support during this event, one example of which was a mass reposting of “Beware the Spinal Trap” coordinated by Sense about Science.  Such advocacy is not without its risks, as both Simon Singh and now the Australian Skeptics can testify.

The Australian Skeptics is a coalition of volunteer advocacy groups dedicated to the advancement of science and reason.  Among their many interests, they’ve chosen to be outspoken advocates for evidence and science-based medicine, using both traditional and “new media” to great effect. That they were among the many to support Singh by reposting his article in late July should have been no surprise; the trouble that simple reposting has caused them, however, was.

Evidently their re-posting of “Beware the Spinal Trap” raised the ire of an Australian chiropractor, Joseph Ierano.  Shortly after sending a lengthy letter to the Australian Skeptics objecting to the content of Singh’s article, he submitted a complaint to the HCCC claiming that by posting Singh’s article, the Australian Skeptics were offering incorrect medical/health care advice and should be subject to the Australian Public Health Act of 1993.  Their subsequent exchanges can be found here.

Which of course brings me to the second bit of good news.  I am happy to report that on October 23^rd the Australian Skeptics received word that the HCCC of NSW dismissed the complaint filed against them by Joseph Ierano, citing that the Australian Skeptics were not health care providers and therefore did not fall under their jurisdiction.  Joseph Ierano, however, certainly is a health care provider and makes some rather interesting claims on his own site that might not have the firmest of foundations.  I wonder if he really intended to bring himself to the HCCC’s attention.

I heartily congratulate both Simon Singh and the Australian Skeptics that their respective cases have taken turns in their favor, and in support of good science.  Though I’m sure the Australian Skeptics would have relished the opportunity to defend themselves and explore the accuracy of statements made by Singh and Ierano in open court (they’ve said as much on their site), I rather prefer that it didn’t come to that.  Given that legal decisions can impact the public perception of the science but have no bearing on its validity, courtroom battles tend to be high-risk and low-gain for those of us promoting science-based medicine.

Mercola.com is a horrible chimera of tabloid journalism, late-night infomercials, and amateur pre-scientific medicine, and is the primary web presence of Joseph Mercola.  Unfortunately, it is also one of the more popular alternative medicine sites on the web and as such is uncommonly efficient at spreading misinformation.  I am not a fan, and have addressed his dross in the past.

Joseph Mercola has recently posted an excerpt from an individual he evidently holds in high regard, Bill Sardi.  Bill published “18 reasons why you should not vaccinate your children against the flu this season.”  Mercola chose his nine favorites (one would assume the nine best reasons), and re-posted it on Mercola.com.  There are so many mistakes, so much misinformation in so little space, it’s almost a work of art.  You know, like that crappy art that you might expect to find on the wall at an hourly motel.  Without further delay, let’s examine Mercola and Sardi’s nine best reasons for you not to vaccinate your children against influenza this season:

1.        The swine flu is simply another flu. It is not unusually deadly.

“Not unusually deadly.”  Oh good, then we can expect only ~36,000 people to die from it this year!  Why does that number not reassure me?

One could do an entire post on just this single misleading claim.  Oh wait, we have.   Suffice to say every influenza strain has unique characteristics, some subtle (like the differences between seasonal strains from 2005-2007), some glaringly different (like the pandemic strains of 1918, 1957, and 1968, or the H5N1 “bird flu”).  Saying something is “simply another flu” is nearly meaningless.

I’ll be charitable and assume he meant 2009 H1N1 is behaving like the average seasonal influenza.  Let’s see, it circulated during the Summer, when flu doesn’t circulate, is uncommon in the elderly, is disproportionately infecting and hospitalizing younger people, it has a much higher incidence of ARDS requiring mechanical ventilation and heart-lung bypass (ECMO) than its seasonal counterpart (Australia reported 68 cases requiring ECMO vs. 4 the prior year), and it has a population which under the age of 60 is nearly 100% susceptible.  Yep, sounds like any old flu to me.

Score: 0/1

2.        This is the first time both seasonal and pandemic flu vaccines will be administered. Both seasonal flu and swine flu vaccines will require two inoculations. This is because single inoculations have failed to produce sufficient antibodies. This is an admission that prior flu vaccines were virtually useless. Can you trust them this time?

Yes, this is the first time they will be co-administered because pandemic 2009 H1N1 didn’t exist before now.  Neither seasonal nor 2009 H1N1 vaccines will require two doses; both have been found to generate a sufficient immune response without a second dose.  The exception to this is in children 6 months to 9 years of age, who require a second dose of the 2009 H1N1 vaccine separated by 4 weeks, and two doses if it is their first time being vaccinated against seasonal influenza.

Even when vaccines do require a second dose, this is not an admission that the vaccine is useless.  Basic (and I’m talking 101-level basic) immunology explains why some molecules and microbes are more immunogenic than others, and require repeated exposures to generate an adequate immune response.

Furthermore, administering multiple vaccines against multiple strains of influenza simultaneously isn’t exactly pushing the boundaries of science.  In fact, it’s status quo: the seasonal influenza vaccine is a trivalent vaccine, meaning that it has three different influenza strains in it.  This has been true every season since the last major shift in circulating seasonal influenza viruses.

Score: 0/2

3.        Adjuvants are added to vaccines to boost production of antibodies but may trigger autoimmune reactions. Some adjuvants are mercury (thimerosal), aluminum and squalene. Why would you sign a consent form for your children to be injected with mercury, which is even more brain-toxic than lead?

Adjuvants are indeed added to some vaccines, and that’s a good thing.  But it isn’t needed in this one, so it’s not there.  I think someone both wise and handsome covered this somewhere on this blog before…  Aluminum and squalene-containing compounds are the adjuvants most commonly used, and both are safe.  However, thimerosal isn’t an adjuvant, it’s a preservative to prevent bacterial contamination of the vaccine and keep it safe.  There is a subtle difference between a preservative and an adjuvant.  For those with sarcasm impairment, by “subtle difference” I in fact mean “blatantly obvious and inexcusable difference.”

And while we are on the topic of influenza vaccine and thimerosal, the single-dose syringes have no thimerosal.  Only the multi-dose vials contain any thimerosal, with each dose containing 25 micrograms of ethylmercury.  This 3.5 times less than what you would get from eating a single can of tuna (~87 mcg), is a form of mercury far more rapidly cleared than most environmental mercury exposures (methylmercury), and has been exonerated from suspicion as a cause of autism.

Score: 0/3

4.        This is the first year mock vaccines have been used to gain FDA approval. The vaccines that have been tested are not the same vaccines your children will be given. (Emphasis Mercola’s)

Wait, what?  “Mock” as in “fake?” You are going to claim something like that and give no source?  None?  Awesome.  Were that to be true, it would be beyond a scandal, it would be criminal, and I’d be right there beside you calling for prosecution.  Were it true.  Which it’s not.  The 2009 H1N1 vaccines were approved as a “strain change” to the seasonal influenza vaccine.   We change the strains almost every year, and the 2009 H1N1 vaccine that your child will be given has been subjected to the same testing as the yearly influenza vaccine prior to release.  Oh, and I’ll provide sources.

Score: 0/4

5.        Over-vaccination is a common practice now in America. American children are subjected to 29 vaccines by the age of two. Meanwhile, veterinarians have backed off of repeat vaccination in dogs because of observed side effects.

Over-vaccination!  Don’t you just hate it when you just aren’t susceptible to quite enough diseases? Children are not subjected to 29 vaccines by the age of two, not even by adulthood.  There are 17 discrete vaccines (including 2009 H1N1) against specific viruses and bacteria on the routine schedule.  Some are combined together in a single injection (like Diphtheria, Tetanus, and Pertussis) to reduce the number of injections.

Where did this number of 29 vaccines come from?  If he meant 29 exposures to individually targeted viruses or bacteria or counting individual antigens he significantly undercounts.  He might come close to the highest number of individual injections a child could get if one avoids most combination vaccines, though given number of different combination vaccines available, the actual number varies.  No matter how you slice it, his number is wrong and misleading.

What about the veterinarian story?  He’s referring to “vaccinosis,” which is more or less “vaccines cause autism” for animals.  That veterinary vaccination schedules have changed is primarily due to a lack of good data in animals and the fact that vets care for widely varying species.  As vets learn more about the immunologic response in a particular species, they follow the evidence and alter their schedules.  This has no bearing on vaccination of humans.

Even if it were an accurate or relevant piece of information, the vets would not be alone in stopping the use of a vaccine due to observed side effects.  Emphasis here on the word “observed,” and not “imagined.”  For example, due to our standard post-licensure surveillance, within a year of its release the original rotavirus vaccine was found to cause intussusception in 1/10,000 children, and was rapidly pulled from the market.

Score: 0/5

6.        Modern medicine has no explanation for autism, despite its continued rise in prevalence. Yet autism is not reported among Amish children who go unvaccinated.

Ignorance of medicine, autism, vaccines, and the Amish, topped off by a non sequitur.  Wow.

Though the causes of autism are incompletely understood, modern medicine is making continual progress.   Studies of twins with autism, along with an increasing number of implicated genes show that autism has a very strong though complicated genetic basis.  Given autism’s heterogeneity, it is unlikely that a single cause will be found that explains all cases of autism, and it is possible that other factors beyond genetics may play some role.  Regardless of what etiologies are eventually found, some potential causes have been ruled out, including vaccines.

The apparent rise in autism prevalence is largely explained by a broadening in diagnostic criteria and increased recognition and diagnosis.  This explanation is further supported by studies like the one just published in the UK demonstrating equal numbers of autistic people in all age groups.

As far as the Amish are concerned, they do vaccinate, and they do have children with autism.

Score: 0/6

7.        Researchers are warning that over-use of the flu vaccine and anti-flu drugs like Tamiflu and Relenza can apply genetic pressure on flu viruses and then they are more likely to mutate into a more deadly strain.

So close!  Antiviral drugs do place selective pressure on replicating viruses, and resistant strains can be produced.  However, drug resistance is not equivalent to virulence, and so his implication that use of antiviral medication will induce more deadly strains is unwarranted.

It is also irrelevant to his topic of “Why you shouldn’t vaccinate your children against influenza.”  If anything, his fallacious argument would support vaccination, because fewer children infected will mean fewer children taking antivirals.

It seems to be asking a lot to expect internal consistency.

Score: 0/7

8.        Most seasonal influenza A (H1N1) virus strains tested from the United States and other countries are now resistant to Tamiflu (oseltamivir). Tamiflu has become a nearly worthless drug against seasonal flu.

Again, half-truths.  Here’s the actual data:  Seasonal influenza A (H1N1) is 99.6% resistant to Oseltamivir.  However, seasonal influenza is typically comprised of three circulating strains, and the other two, A (H3N2) and influenza B, are 100% susceptible to Oseltamivir, as is 2009 H1N1.  That’s hardly “nearly worthless.”  Furthermore, seasonal influenza A (H1N1) is highly susceptible to the Adamantanes (though H3N2 and type B are resistant), and we have no resistance of any influenza to Zanamivir.  This is well known to physicians.  We are able to type the influenza a patient is infected with and tailor their therapy when necessary, and continually monitor the susceptibility of circulating strains as you can see on the CDC site.

And again, what does this have to do with vaccination?

Score: 0/8

9.        Public health officials are irresponsible in their omission of any ways to strengthen immunity against the flu. No options outside of problematic vaccines and anti-flu drugs are offered, despite the fact there is strong evidence that vitamins C and D activate the immune system and the trace mineral selenium prevents the worst form of the disease.

“Strong.”  I do not think that word means what you think it means.  While it is true that deficiency in Vitamin C, Vitamin D, and selenium can make you more susceptible to infection, (unlikely in a developed country, but possible), there appears to be no benefit in further supplementation in the general population. Furthermore, we have reason to suspect that blanket recommendations of the use of antioxidants like Vitamins C and D and selenium may cause an increase in mortality.

Public health officials do make recommendations other than vaccines and anti-virals to avoid contracting influenza.  You can find them right here.  The problem (from Mercola’s point of view) is that they only endorse effective interventions based on proper evidence.  When there is limited plausibility for an intervention to work, little evidence in favor of it, and significant evidence suggesting futility or even harm from its use as is the case with these supplements, the appropriate action is to not recommend its use.  Which as Mercola points out, is exactly what public health officials do.  Responsibly.

Score: 0/9

Ooooh, swing and a fumble, 9 strikes, you’re out!  Swing and a line fault?  Whatever, I’m rubbish with sports, kind of like Mercola and Sardi are rubbish at medicine.  Out of their “9 best reasons not to vaccinate your child,” none of them are valid, and two of them don’t even concern vaccination.  Every single point here is utterly wrong, wantonly ignorant, and one would almost think intentionally misleading.

If I sound upset, it is for good reason.  For while Mercola and Sardi, drowning in their arrogance of ignorance, spread their misinformation with the expressed intent of undermining the public trust in vaccination and modern medicine, my colleagues and I will be forced to deal with the aftermath. This season has already been an unpleasant one in my pediatric ICU.  During what is traditionally the slowest part of the year, we are running at near our capacity of 26 beds.  The fraction of our patients who are in the ICU with 2009 H1N1 has steadily increased since the school year began, from roughly 5-10% of our census being flu positive over the summer (which is odd in itself), to now between 30-50%.  The need for prolonged mechanical ventilation is common in these patients, we have needed to place three children on a heart-lung bypass machine (ECMO), and tragically we have had deaths.

My ICU experience is typical rather than exceptional.  If you have any interest in following this influenza season, the single best source of up-to-date information is the CDC’s FluView Weekly Update.  There you will see that the percentage of visits to the ED for influenza-like illness is markedly elevated above the expected baseline, that the number of lab-confirmed influenza hospitalizations has tripled in the last 5 weeks, that at the present, the very beginning of the traditional influenza season, the age groups between 2 and 64 years of age have met or exceeded their average total number of influenza cases usually seen at the end of the season (~May).  Most depressingly, you can see the number of influenza-related pediatric deaths is growing, and growing rapidly.  Furthermore, this month’s JAMA has released studies from Canada, Australia/New Zealand, and Mexico describing their experience with critically ill patients with 2009 H1N1 that are similar to my own.

Most people who contract influenza are miserable for about a week, but recover, usually without the need for medical care.  The ICU experiences I relay here thankfully do not represent the population at large, but are meant to serve as a reminder that while you may not suffer from influenza this season, your neighbor may not be so lucky.  Influenza is a real threat, it deserves our respect, and our fellow citizens deserve to be properly informed and empowered to protect themselves and their loved ones. Influenza is not benign, and neither is the medical advice being distributed by Joseph Mercola.  The stakes are measured in human suffering and human lives, and Mercola bears responsibility for undermining the public health.

Most of these concerns bear consideration (though I have no time for those who advocate using the threat of disease and death to force conformation to their religious beliefs), and were in large part addressed by David Gorski in a SBM article last year.  If you’ve not read his post, I strongly suggest you do so.  Now that a large post-licensure study on qHPV has been published, it seems a good time to revisit the issue of greatest concern to me as a pediatrician and to most parents, namely qHPV’s safety and efficacy profile.

THE PROBLEM OF HPV INFECTION

Infection with HPV is a common problem, infecting 79% of the population over their lifetime, and holding the dubious honor of being the most common sexually transmitted disease. In addition to genital warts, HPV infection has been clearly shown to be responsible for a large percentage of cancers in areas that contract HPV, including the vulva, vagina, and penis (40%), anus (90%), and oropharynx (12%), but the most common site of HPV-caused cancer is the cervix.  Cervical cancer is diagnosed in 7.9/100,000 women per year, amounting to approximately 11,000 cases in 2008 and 3900 deaths in the US.  Worldwide, the WHO estimates 500,000 cases of cervical cancer and 260,000 related deaths.

We have largely failed in preventing HPV infection.  Infections are not always obvious and are thus hard for sexual partners to identify and avoid.  Barrier devices like condoms don’t cover all the potential infected areas (see the list above) and are thus helpful but of limited utility. Education and abstinence are clearly inadequate to fully address the problem.

In spite of our limited ability to prevent HPV infection, gynecologists have made significant progress in reducing the number of women who suffer from cervical cancer, in large part through regular screening with Pap-smears.  The ability to identify and treat pre-cancerous lesions on the cervix or to identify cervical cancer early in its course has lead to a marked reduction in deaths from cervical cancer in the US.  It has been so effective that one of the highest risk factors for developing cervical cancer is now a failure to obtain routine Pap-smears.

Yet in spite of the success of Pap-smear screening, we were still faced with 11,000 cases of cervical cancer and 3900 deaths last year.  Through sustained effort and eternal vigilance on the part of patients and physicians we can reduce the impact of HPV induced malignancy, but the population at risk remains unchanged.  And let’s be honest, humans suck at eternal vigilance.  If we could prevent the infection, we could prevent its complications and reduce the impact of the inevitable lapse in our eternal vigilance.  Vaccines allow us to do exactly that.

THE HPV VACCINE’S EFFICACY

qHPV is a vaccine against the two most common causes of genital warts (types 6 and 11) and the two leading causes of cervical cancer (types 16 and 18).  Its antigen is a virus-like particle with no genetic material, so it is not a live-virus vaccine and cannot cause infection.  It has an excellent response rate, inducing an adequate antibody response to all four types of HPV in 99.5% of women after the third dose that has been shown to persist for at least five years.

Regarding efficacy, most cervical cancer occurs decades after the infection, so it will be quite some time before we can demonstrate the effect qHPV should have on the incidence of cervical cancer.  However, lesions identified on Pap smear and known to precede cervical cancer occur far earlier, and have served as a surrogate in pre and post-licensure studies.  In trials to date, qHPV is 94-100% effective at preventing pre-cancerous changes from these four HPV types.

THE HPV VACCINE’S SAFETY

qHPV is effective, but what of its safety? When it was submitted for licensure, over 20,000 women between the ages of 16 and 26 (the peak ages during which most women are infected) were enrolled in phase 3 trials.  Potential adverse events were solicited from all participants were nearly identical between the test and control groups.  The only reactions that stood out when compared to the control group were fever (13% vs 11.2%), nausea (6.7% vs 6.5%) and injection site reactions (2.2% vs 0.9%).  No serious reactions were seen.  Based upon this information, qHPV was considered to be safe and approved by the FDA.

Since its release, however, there have been reports of serious adverse reactions following qHPV injection.  Many articles voicing concerns about its safety cite the VAERS database. These reports have generated headlines in the mainstream media, not to mention being perpetual fodder for crank sites like NaturalNews and Whale.to., and have been a if not the major source of the concern expressed by parents.

As a part of routine post-licensure follow-up and to address these very concerns, “Postlicensure Safety Surveillance for HPV Vaccine” was funded by the FDA and CDC and published last month in JAMA. This article is the largest attempt to evaluate the adverse events seen since qHPV was released.  In it, the authors compared the adverse events reported to VAERS to the expected background rate of reported events in the unvaccinated general population of women aged 9-26, re-evaluating the previously reported adverse events known from licensure as well as the reports of more serious events that have gained public attention.  The results are reassuring.

Over the first 2.5 years since its release, 23 million doses of qHPV were administered, and VAERS received 12,424 reports of adverse events.  Of these, only 772 (6.2%) were classified as serious or life-threatening. These are summarized in the table below, taken from the article:

Of all of these events, only two are above what one should expect from their respective baseline rates and not previously identified by the original licensure studies.  The first is Venous Thromboembolic Events (VTEs).  These are blood clots within the blood vessels that can be quite serious; these occurred in 0.2/100,000 doses.  The second was syncope, or loss of consciousness, which occurred in 8.2/100,000 doses.  This does not establish that qHPV causes these events; remember that this study and the VAERS in general are not designed to establish causation.  Nevertheless, further studies are certainly warranted to confirm or refute qHPV’s role in these rare events, and physicians should bear the correlation in mind when considering the administration of qHPV.

Notice, however, that the rates of major events of concern, namely Guillain-Barre syndrome, autoimmune disorders, transverse myelitis, and death, were all exceedingly rare, and not above what one would expect to occur in the normal unvaccinated population.  In spite of the clear limitations inherent in the use of the VAERS database, this study should strongly reinforce the confidence of physicians and parents regarding the safety of HPV vaccination.

Gardasil (qHPV) is a new vaccine.  Recommendations regarding its use are likely to continue to change as we learn to optimize its use.  Just last week, an FDA advisory panel recommended that qHPV be approved for use in males age 9-26, and Merck is likely to seek approval to broaden the approved ages of administration.  Whether these developments should alter the current practice is a point of open debate.  And of course, as with any new medical intervention qHPV warrants close surveillance for any unexpected adverse effects. Though uncertainties remain regarding this vaccine’s use in the sphere of public health, for a parent who desires to reduce the risk of HPV infection and HPV induced malignancies for their child, we can confidently say that qHPV is a safe and effective option.

I find it is best to start at the beginning.

What Is Influenza?

Within the public sphere, “The flu” has become shorthand for “I feel like crap.”  I suspect that this is part of the reason why some people think the influenza vaccine doesn’t work.  Medically speaking, however, influenza is a very specific family of viruses that cause a reasonably narrow set of problems for humans.

The influenza season in the Northern hemisphere usually runs from October through May, with a peak mid-February.  Every season in the US between 5-20% of the US population is infected by influenza, and while the majority of people recover well from an influenza infection, not everyone will.  Annually 200,000 people are hospitalized, and on average 36,000 will die either from influenza or its complications.

The classic influenza infection incubates for 1-4 days after exposure.  Its onset is rapid, with most people experiencing high fever, headache, muscle aches, dry cough, sore throat, and nasal congestion.  Gastro-intestinal symptoms like nausea, vomiting, and diarrhea are less common.  Symptoms last from several days to almost two weeks, and a person is contagious from one day before symptoms begin to more than a week after symptom onset.

There are many strains of influenza. The current seasonal influenza is made up of three different influenza subtypes: A(H3N2), A(H1N1), and B.  Don’t confuse the seasonal A(H1N1) strain with the current pandemic 2009 A(H1N1); they are distinct.  I will refer to them as A(H1N1) for the seasonal strain, and 2009 (H1N1) for the pandemic “swine flu” strain.  Influenza B is less common, less virulent, has a slower mutation rate, and is thus a lesser risk; the rest of this discussion is focused on Influenza A.

How Does Influenza Spread?

Influenza has two dominant modes of transmission: droplet and contact transmission. Droplet means that when someone coughs or sneezes, extremely fine (and sometimes not-so-fine) droplets are aerosolized into the air around them.  If these droplets come in contact with your nose, mouth, throat, or lungs, it is possible for you to become infected by the viruses in those droplets.

The second way influenza can be spread is either through direct contact or through an intermediate like a doorknob, known as a “fomite.”  The virus can survive for minutes to days depending on the surface, and if you touch that surface then your mouth or nose, again, it is possible that you can become infected.  Influenza does not appear to be capable of spreading long distances through the air (across large rooms or through air vents).

How Does Influenza Change?

Influenza A is a versatile virus with many distinct serotypes.  Most people are familiar with human, bird, and swine influenza, but influenza is in fact able to infect a large number of avian and mammalian species on the planet.  It is important to realize that these viruses are not, despite their name, truly species specific. Random mutations and natural selection frequently create new strains of influenza capable of infecting other species; in its ability to mutate influenza is unparalleled.

Influenza is an RNA virus encoded by just 11 genes on 8 separate RNA segments.  With only 11 genes, you can see that influenza is a relatively simple virus.  But its simplicity is one of the most significant reasons for its success.  Unlike our DNA, the RNA of influenza replicates without the benefit of enzymes that correct transcription errors.  This means that it makes more transcription errors, a lot more.  One in every 1000-10,000 nucleotides is mis-transcribed by influenza, giving it one of the highest mutation rates known.  Some of these errors are neutral and have no effect on the virus.  Some are detrimental and will result in a defective virus.  But some of them are beneficial.  Two genes encode influenza’s characteristic surface proteins hemagglutinin (HA) and neuraminidase (NA).  There are 16 types of HA, 9 of NA, and respectively these two proteins serve to bind the virus to a target cell and to release new viral particles from a host cell, and they also happen to be the parts of influenza the immune system recognizes.  Every so often a transcription error will change the conformation of either HA or NA just enough so that it cannot be recognized by the immune system.  Voilà, we have a new strain of influenza, and your immune system has to start from scratch.  This is the concept of “antigenic drift,” and it is responsible for the variation in influenza strains we see every year.

But that is only part of the story.  Do you remember the 8 separate RNA segments?  If a cell is infected with a single strain of influenza this is an inconsequential factoid.  However, if two dissimilar strains of influenza co-infect the same cell, those 8 RNA segments become exceedingly important.  Up to 256 unique combinations can result from that one pairing.  Instead of a slow drift in the surface markers of the circulating influenza strains, suddenly we have a major re-assortment, and a brand-new strain is created.  This is “antigenic shift,” and this is how the 2009 (H1N1) strain was born.

I hope it is clear at this point that influenza is not a single virus that changes over time, but is instead a family of viruses that to a greater or lesser extent co-exist and are constantly changing.  Were it stable, your immune system would be able to establish meaningful immunity.  Until we discover a way to make your immune system target a stable section of influenza, our best hope is to constantly redesign our vaccines against a moving target.

What Makes the Novel Influenza A 2009 (H1N1) So Special?

Other novel influenzas have been identified in the past without causing a pandemic.  The 1976 swine flu is a prime example.  Identified in Fort Dix, it infected at least 13 soldiers, killing one.  It looked similar to the 1918 Spanish flu, which raised concerns of a potential pandemic and triggered a mass vaccination campaign. Yet it never spread beyond the base and has not been seen since.

Another example is the H5N1 “bird flu” that we’ve heard about since its emergence in 1997.  It has had several outbreaks, caused over 167 deaths, and carries a ~60% mortality rate for those infected.  Fortunately, though it can spread like wildfire through birds, and humans can catch it from birds, humans cannot reliably spread it to other humans.  Thus it is a virus with the potential to be truly terrifying, but in its current state poses a limited infectious risk.

Why then are we so confident that the 2009 (H1N1) strain will behave differently and pose a real risk? Three reasons:

First, recall that the 2009 (H1N1) is distinct from the seasonal A (H1N1).  It appears to be a “triple recombination,” with characteristics derived from human, bird, and swine influenzas.  When our population was tested for antibodies against 2009 (H1N1) nearly no children, and less than 10% of those under the age of 65 had reactive antibodies, and of those over 65 only 33% showed any response.  It seems no one has seen a similar influenza in half a century.  This means that the vast majority of our population is susceptible to infection this season; you can see the potential for infection on a grand scale.

Second, unlike the 1976 strain, the 2009 (H1N1) has already proven itself to be highly contagious.  From its first appearance in Mexico on March 18^th, 2009, it took 4 weeks to spread outside the borders of Mexico, and within 2 more weeks it was in 5 states and 8 other nations. Only 6 weeks after being first identified, over 3000 cases were to be found in 43 states and 23 countries, and on June 11^th, 2009, after only 3 months, it had achieved pandemic status.  Furthermore, it was able to accomplish all this during the season least conducive to its normal spread.

Finally, the 2009 (H1N1) has proven itself to be far from benign.  As of August 22^nd, the US has hospitalized 8,843 people with 2009 (H1N1), and 556 have died, 101 of them under the age of 24.  We have a hospitalization rate of 4.5/100,000 for ages 0-4, and 2.1/100,000 for ages 5-24.  All of this, recall, has happened during influenza’s off-season.

In areas where 2009 (H1N1) emerged during the traditional influenza season, like Australia, they have reported more than a doubling in the number of people hospitalized from influenza, with around 1 in 5 requiring ICU-level care.  Similar to what we have seen in the US, Australia has likewise demonstrated that 2009 (H1N1) has a higher attack rate in younger people, which is in stark contrast to the normal seasonal influenza pattern, and has shifted its mean age of death from influenza from 83 down to 54.  Unlike what we have seen thus far, Australia has had a much higher hospitalization rate of 34.6/100,000 in ages 0-4, and an overall rate of 12/100,000 for the population.  This likely reflects the differences between being on-season and off-season.

That is what makes 2009 (H1N1) so concerning.  It is capable of causing serious infections even and perhaps especially in the young and the healthy.  It is highly contagious, it has a worldwide population without immunity, and it now exists in low levels in most communities around the nation.  And we are now entering into its prime season.

Conclusion

So is this the Zombie Apocalypse, or only slightly less concerning, is this going to be a repeat of the 1918 Spanish influenza pandemic? Almost certainly not.  Nor, however, were the predictions made by the President’s Council of Advisors on Science and Technology outlandish fear mongering.  30,000 dead is an average influenza season, and if we see a simple doubling in the number of cases we will rapidly approach the higher end of their estimate.

Influenza warrants our respect and attention.  I hope these estimates are higher than what we will in reality see; it would make my winter in the ICU far more pleasant.  The fact remains that only time will tell.  In the meantime, we would be wise to be prepared.

So what can you do?

• Get vaccinated against seasonal flu and 2009 (H1N1) – It’s cheap, safe, and effective. If you don’t get sick, you avoid all of the risks of infection while also avoiding the responsibility of infecting others.
• Wash your hands – You should be doing this anyway.
• Cover your cough and sneeze – It’s just polite not to spray your mucous in my face.  Thank you.
• If you are ill stay home until 24 hours after your fever abates – If you are infected, there is no reason to risk the health of everyone around you.
• Don’t Panic – Most people will get through an influenza infection without medical attention.  Rest, stay hydrated, and minimize your exposure to others.

The CDC recommendations for warning signs to seek medical care are as follows:

In children, emergency warning signs that need urgent medical attention include:

• Fast breathing or trouble breathing
• Bluish or gray skin color
• Not drinking enough fluids
• Severe or persistent vomiting
• Not waking up or not interacting
• Being so irritable that the child does not want to be held
• Flu-like symptoms improve but then return with fever and worse cough
• Any child under 12 weeks of age with fever over 100.4 F (38 C)

In adults, emergency warning signs that need urgent medical attention include:

• Difficulty breathing or shortness of breath
• Pain or pressure in the chest or abdomen
• Sudden dizziness
• Confusion
• Severe or persistent vomiting
• Flu-like symptoms improve but then return with fever and worse cough

Too often in medicine we find ourselves confronted with problems we cannot fix.  Some traumas are too severe, some infections have too much of a head start.  Some diseases are poorly understood, while others have no known treatment.  One of the darker adages of medicine still holds true: In spite of all our advances, the world mortality rate seems to be holding quite steady at 100%.

Thankfully, influenza is not a disease against which we are helpless. We have ways to limit its spread, and medicines with a modest effect in assuaging symptoms and shortening the length of illness.  Most importantly, we have vaccines that can safely prevent the disease altogether.

There are myriad misconceptions and fears surrounding the influenza and its vaccines, most are not new and have been addressed elsewhere, including the concern that the influenza vaccines cause the flu (they don’t), that the thimerosal they contain causes autism (it doesn’t), and that it can trigger Guillan Barre Syndrome (it can³, at a rate of 1/1,000,000, similar to the background rate of Guillan Barre in the population⁴).  The confusion has been compounded by the emergence of the novel H1N1 pandemic.  With so much at stake, it is exceedingly important to have clear, accurate information available to physicians and the public alike.

Dr. Joseph Mercola’s recent screed foisted upon the public is no such source.  “Squalene: The Swine Flu Vaccine’s Dirty Little Secret” reveals his exceptionally poor grasp of the immune system, asserts that influenza is not worth preventing (36,000 deaths, 200,000 hospitalizations from seasonal flu, I suppose one could see his point), and perpetuates the thoroughly refuted toxin gambit. Nevertheless, at the time of this writing his article has misinformed nearly 250,000 readers.

If Thousands of Children Aren’t Dying It Can’t Be That Bad

His article begins with his confession that he doesn’t understand why children should be vaccinated against influenza.  After all, in his own words:

Less than 100 children in the US die each year from seasonal flu viruses… If children are the first target group in the U.S. per Sebelius, that means we’re about to inject around 75 million children with a fast tracked vaccine containing novel adjuvants, including dangerous squalene, to prevent perhaps 100 deaths.

First off, the groups given the highest priority by the CDC and HHS as outlined by Kathleen Sebelius for H1N1 vaccination are:

• Pregnant women
• Health care and emergency workers
• Caregivers and close contacts of children under 6 months of age
• Anyone between the ages of 6 months and 24 years old
• Adults with a subset of chronic medical conditions

These groups differ from the seasonal influenza recommendations due to the behavior of H1N1 since its emergence.   Thus far, more than 70% of US H1N1 cases have been in people under the age of 24, and children less than 4 years of age have had the highest rate of hospitalization.  The recommendations are designed to protect those at the highest risk of complications and death, and given that the groups targeted encompass more than half the US population (approx. 159 million people), children are hardly being singled out for experimentation as he implies.

Second, in discussing only the children who die, Dr. Mercola implies that the only benefit of vaccination is the prevention of death in the person vaccinated.  People aren’t either healthy or dead.  Those who survive an infection are still subject to its inherent suffering and complications.  Furthermore, survivors run a high risk of spreading it to others who then share in the risk and misery.  Dr. Mercola doesn’t seem to appreciate that children suffer the greatest rate of infection from seasonal flu each season (10-40% of all children are infected each year, ~1% of all infected children are hospitalized), and are therefore the primary source from which influenza spreads (that’s the “infectious” part of an infectious disease, I know, it’s subtle) to the rest of the population.  By immunizing children against influenza we not only save their lives, we also reduce the burden of disease on the elderly who make up the bulk of the 36,000 seasonal influenza deaths each year.  We do not vaccinate “to prevent perhaps 100 deaths,” we vaccinate to prevent a disease altogether, and to help the entire population avoid all of these risks.

Preventing children from contracting influenza, either seasonal or H1N1, is a very rational, humane goal, and hardly the “ridiculous assumption” Dr. Mercola claims it to be.

Fear Factor: Squalene Edition

After his incredibly callous argument to allow children to contract influenza (I’m paraphrasing for brevity), Dr. Mercola then employs the toxin gambit to assert that the H1N1 vaccine is unsafe.  Here I have to give him credit for promoting yet another molecule to the anti-vaccination list of Chemicals of Omnipotent Toxicity™: Squalene.

The U.S. government has contracts with several drug companies to develop and produce swine flu vaccines. At least two of those companies, Novartis and GlaxoSmithKline, are using an adjuvant in their H1N1 vaccine.

Half-truths are the most dangerous ones aren’t they? Novartis and GSK are indeed developing H1N1 flu vaccines with adjuvants containing squalene.  In fact, they’ve been doing it for more than a decade – but I don’t want to give away the punch line.  Let’s examine the rest of Dr. Mercola’s claims first.

Adjuvants cause your immune system to overreact to the introduction of the organism you’re being vaccinated against.

No.  Adjuvants are used to get your immune system to recognize and react to antigens that do not trigger a sufficient response on their own.  Sometimes this is because the antigens are poorly reactive without being attached to a virus or bacteria like they usually are.  Other times it is because we use such a minuscule amount of antigen compared to what occurs during an infection that it’s invisible to the immune system.  For example, vaccination against Hepatitis B exposes you to a total 30 mcg of antigen compared to 1100 mcg/hour produced during an infection⁶.  Regardless, adjuvants take your immune response from next to nothing to just enough to induce immunity.

Less vaccine required per person means more individual doses available for mass vaccination campaigns. Coincidentally, this is exactly the goal of government and the pharmaceutical companies who stand to make millions from their vaccines.

Dr. Mercola’s on to us!  Maybe he saw the latest batch of H1N1 vaccine delivered in one of our unmarked black helicopters.  We should really be more careful.

It is no coincidence that we are trying to make hundreds of millions of vaccines at a limited cost.  It is fully intentional.  The world is faced with the need to produce hundreds of millions of doses of influenza vaccine with a limited amount of antigen and a limited amount of time.  Failure to meet the demand will result in rationing of vaccine supplies and will leave people vulnerable who desire and deserve to be protected.  Again, we would have needless suffering and lives lost.  If the use of an adjuvant can help meet this demand, reduce costs, and save lives, then yes, it should be strongly considered.

Before I leave this comment, I’ll take the opportunity to point out that pharmaceutical companies, doctors, and hospitals stand to make a lot more money from an uncontrolled pandemic than from its prevention.  The money spent on antivirals, antibiotics, sedation and pain medications, physician and hospital billing for the 200,000 people hospitalized in the US during a normal flu season would compensate them far better than profits from vaccine sales. It’s almost as though, against our financial interest, all of our efforts are designed to keep people from getting sick…

Your immune system recognizes squalene as an oil molecule native to your body. It is found throughout your nervous system and brain. In fact, you can consume squalene in olive oil and not only will your immune system recognize it, you will also reap the benefits of its antioxidant properties.

The difference between “good” and “bad” squalene is the route by which it enters your body. Injection is an abnormal route of entry which incites your immune system to attack all the squalene in your body, not just the vaccine adjuvant.

Your immune system will attempt to destroy the molecule wherever it finds it, including in places where it occurs naturally, and where it is vital to the health of your nervous system.

Gulf War veterans with Gulf War Syndrome (GWS) received anthrax vaccines which contained squalene. MF59 (the Novartis squalene adjuvant) was an unapproved ingredient in experimental anthrax vaccines and has since been linked to the devastating autoimmune diseases suffered by countless Gulf War vets.

There are several points that could be addressed in this section, including anti-oxidant abuse, the childish (and incorrect) description of “good” and “bad” squalene, and the evidence refuting the claim anthrax vaccine given to Gulf War vets contained squalene, much less that it is the cause of Gulf War Syndrome (GWS).  However, the main claim Dr. Mercola makes here is that squalene, when injected, will trigger an immunologic response and that these squalene-specific antibodies will then cause untold havoc in your body.  That’s a testable hypothesis, and don’t you know scientists just love to test hypotheses?

To support his assertion he cites a small cohort study from 2000 that reported anti-squalene antibodies in veterans afflicted by GWS.  Case closed, right?  Not so much. A larger and better-designed study found no correlation between the presence of squalene antibodies and symptoms of Gulf War Syndrome.  More important regarding vaccine safety, a subsequent study  using more sensitive and accurate methods than those used in the study by Asa established that anti-squalene antibodies are present in a large percentage of adults regardless of exposure to squalene from vaccines, and are unchanged by subsequent exposure to squalene containing adjuvants.

In other words, adjuvants containing squalene don’t induce an immune response to squalene.  No antibodies are created to cause whatever autoimmune phenomena Dr. Mercola cares to postulate, including GWS.  His hypothesis fails.

There is virtually no science to support the safety of vaccine injections on your long-term health or the health of your children. Follow-up studies last on average about two weeks, and look only for glaring injuries and illnesses.

This is simply untrue.  Post-licensure surveillance for vaccine safety is among the most extensive in medicine.  Squalene-containing vaccines are no exception.  As of 2009, over 40 million people have been given squalene containing influenza vaccines in Europe.  The incidence of serious adverse events so far reported, 1.4/100,000 doses administered, is at the baseline of the general population with no exposure to the vaccine.

As far as long-term follow-up, squalene has been studied as part of influenza vaccines in over 30 phase 1-4 trials, 13 of which had 4-6 month follow-up, and included over 14,000 people, and the current influenza vaccines in development are subject to clinical trials with a 6-12 month follow up schedule.

THE PUNCH LINE

With his article Dr. Mercola sought to scare people away from vaccinating against influenza in general, and H1N1 in particular.  Contrary to Dr. Mercola’s poorly informed assertions, cherry picked and outdated studies, and outright misinformation, influenza is a real threat and vaccines against it are both effective and safe.

Ah, but earlier I promised you a punch line. Remember this quote?

The U.S. government has contracts with several drug companies to develop and produce swine flu vaccines. At least two of those companies, Novartis and GlaxoSmithKline, are using an adjuvant in their H1N1 vaccine.

Novartis and GSK are indeed developing influenza vaccines containing adjuvants – for use in Europe, where squalene containing adjuvants have been safely used for over a decade.  The US is indeed conducting H1N1 vaccine safety and efficacy studies that include the use of adjuvants.  Given the unpredictable nature of the upcoming season and the very real potential that vaccine demand will outstrip its supply, it would be irresponsible for the US not to be prepared with a well studied contingency plan that includes possible adjuvant use.

However, it must be clearly stated that there are no adjuvants, nor have there ever been, in the US influenza vaccines.  Furthermore, barring the highly unlikely failure of the standard unadjuvanted vaccines currently in trial, the H1N1 vaccines available in the US will also be adjuvant free.⁷

Even if Dr. Mercola’s entire article made a single valid point regarding the use of adjuvants in the H1N1 vaccine, it is irrelevant to the US population.  Based on poor science, packed with misinformation, and designed to promote unwarranted fear, his article is not a source of information, it is dangerous, irresponsible fear mongering.

Citations:

1. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289:179–86.
2. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292:1333–40.
3. Guarino M, Casmiro M, D’Alessandro R. Campylobacter jejuni infection and Guillain-Barre syndrome: a case-control study. Emilia-Romagna Study Group on Clinical and Epidemiological problems in neurology. Neuroepidemiology 1998;17:296–302.
4. Haber P, DeStefano F, Angulo FJ, et al. Guillain-Barre syndrome following influenza vaccination. JAMA 2004;292:2478–81.
5. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004 Sep 15;292(11):1333-40.
6. Courtesy of Quackcast, Episode 30, 2/22/2009, by Mark Crislip. http://www.quackcast.com/spodcasts/files/48f9db861d8a83f764792aa4b77990f8-29.html
7. This decision drew heat from the international medical community, as it runs counter to the World Health Organization’s recommendations, will mean fewer vaccine doses produced overall, and may compromise our ability to control the spread of H1N1 worldwide if supplies fall short.

“Primum non nocere.” First, do no harm. It is a guiding principle of medicine, and one which is next to impossible to achieve in practice. It is difficult for the general public to hear, but any intervention a physician makes, and indeed the decision to make no intervention, carries a risk of harm with it. Given enough time, every physician will make a decision which results in unintended harm to a patient, even death, and it haunts us every day of our careers. Faced with this horrible certainty, what is one to do? The only responsible, ethical position to take is to ensure that each patient receives the care most likely to generate a positive outcome, in other words, to stack the deck as steeply in favor of the patient as is possible. Diligent application of the scientific method to every therapy, novel and new, old and venerated, is the only way we as physicians can be certain we are doing the greatest good and the least harm to those who seek our help; it is the only way to assuage our conscience if things end badly.

Our professional organizations and academic institutions have been vital in formulating, propagating, and enforcing the practice of evidence based medicine (EBM). They have stood, to borrow the phrase from Carl Sagan, as “a candle in the dark,” promoting the best practices and protecting patients from those that are ineffective, fraudulent, harmful, or even simply sub-standard. It is a heartening environment in which to work.

With increasing distress, I and others have watched, and I fear have been complicit in, the assisted suicide of EBM at the very moment it is reaching maturity. While our academic centers have supported EBM, they have simultaneously allowed its antithesis to take root within their very halls under the misnomer of Complimentary and Alternative Medicine (CAM). As CAM is almost by definition non-evidence based, EBM and CAM are guaranteed to come into conflict in practice.

This conflict is one I was certain I would confront in due time, but not on my very first day as a newly minted faculty member. Few things are as stressful to a family as an acute, severe illness. The disruption of normal life, reminder of mortality, financial burden imposed, and in particular the loss of control are trying to everyone who finds themselves in the intensive care unit. These factors are magnified when the victim is a child. When faced with the critical illness of their child, parents will seek help from any source they feel may hold the slightest glimmer of hope. Frequently this will lead them to some form of pseudoscience. It is not uncommon, then, for me to be faced with questions about homeopathic treatment for a child with a severe infection, herbal supplementations for a metabolic disorder, or chiropractic after a car accident.
In most situations, such questions are a request for more detailed discussion about their child, for reassurance, or for insight into what I and the other physicians are actually thinking about. Sometimes a rational explanation of why any given pseudoscience is unhelpful and may put their child at risk is enough to explain why my preferred needle is an IV and not acupuncture. Even in the situation where families are staunch believers in a pseudoscience, most recognize that the intensive care unit is not the place for its application. Such was not the case on my first day.

Among the children in my care was a 6 month old child with a new onset of seizures. He had appeared to be previously healthy, but now was on a breathing machine, heavily sedated, and would seize again whenever his medicine was lightened. Frustrating to his family and his caregivers was the lack of a clear diagnosis, a reason for his aggressive seizures. My team and I took a great deal of time every day to explain what we knew and what the plan, both short and long term was for their child, and even went so far as to involve the family in our daily rounds. In spite of these efforts, their dissatisfaction grew, and their relationship with me and the care team became increasingly antagonistic.

While I worked with many sub-specialists and pursued causes both likely and less so, his family pursued its own investigation. The child’s uncle was a chiropractor, and told them of another chiropractor who claimed to specialize in neurological problems. The family asked on several occasions to have the neuro-chiropractor brought in to the hospital and officially consulted by my team.

Here then, is the crux, the conflict. EBM or CAM? Shall I refuse to involve the chiropractor, as there is no reason to suspect he has anything of value to add, and significant risk to the child can be incurred with manipulations? In refusing the family’s explicit request, I would almost certainly undermine their trust, making it more difficult to provide the care this child will continue to require. In protecting this child from the chiropractor and preserving my academic integrity, I would sacrifice any hope for a healthy collaborative relationship with the family. On the other hand, I could grant the family’s desire to have the chiropractor become a functioning member of the medical team, which would bolster their confidence while exposing the child to risk without benefit, and sacrificing both my and my institution’s academic integrity.

As though this situation were not already difficult, there is precedent within my hospital to allow temporary privileges for chiropractors to see children while they are inpatient when families have requested it. Furthermore, the university we are affiliated with is one of dozens of major institutions which now teach elements of CAM in medical school and who have a section of CAM within the university. Put bluntly, this means that if I as the attending physician were to make a stand at this child’s bedside against the involvement of chiropractic within my ICU, I would not have been supported by my own administration.

In this child’s case, I opted for a compromise between the two polar alternatives I described. I allowed the chiropractor a one time visit to see the child, under the stipulation that his visit be supervised by me while he examined the child, and that no manipulations of any kind would be done before consultation with both myself and the involved neurologist. I would gladly speak to him and the parents together regarding our thoughts on the case, and take his recommendations under advisement, but would be under no obligation to act upon them.

The chiropractor’s recommendations were a bit surprising. He had no interest in spinal manipulations of any kind. The philosophy under which he labored was that he needed to encourage “normal neuronal pathways.” This amounted to gentle tactile stimulation, passive range of motion exercises, having the parents talk to the child, and playing music he claimed was specially designed to stimulate different parts of the brain. He also made dietary and nutritional recommendations, which included continuing to use breast milk (he was stunned and impressed I would “allow” such a thing to happen), and supplementing his mother’s diet with fish oil. Further herbal recommendations were made directly for the child; these I flatly refused to entertain without knowing the exact contents and pharmacologic interactions. In the end, the family was pleased by the visit, we enhanced our relationship with them, and prevented the child from coming to harm.

In this episode, I don’t feel that it was in the child’s best interest to fight the battle between EBM and CAM at his bedside (though I acknowledge that such a fight may be required under different circumstances). In hindsight, though, I feel it could have been handled slightly differently. We frequently have priests, imams, prayer sessions, rabbis, etc visit children within the PICU and make no special arrangements. We will speak to these people about their thoughts on the patient and the family’s condition, if they so desire. We do not, however, seek to give them privileges within the hospital. I think that I should have allowed the family to have the chiropractor visit as they would any other family friend, and if they wanted me to speak with him, I would agree to do so. This would have allowed the family to be heard and to have their needs sated without giving the mistaken impression of treating a chiropractor as an equal.

What are we to make, however, of the situation within our academic institutions? As long as CAM is supported, EBM will remain difficult to practice. The public will become more confused as to what constitutes safe and effective medicine, funds will be wasted on futile projects, and medical progress will be retarded. Most concerning, the next generation of physicians, immersed in the mutually exclusive principles of CAM and EBM will be poorly prepared to provide the best possible care to their patients.

The current political, commercial, and academic powers have been ineffective at preventing the corrosion of the principles of EBM. We have a professional and ethical obligation to strengthen and reform the intellectual infrastructure of medicine. If, however, it is no longer sufficient for physicians to align themselves with existing organizations in order to stand clearly in support of EBM, it may be time to develop a way for physicians and health care professionals who practice science based, evidence based medicine to publicly stand up and be counted.

Primum non nocere. An unattainable goal it may be, but a relentless commitment to EBM is the only way for us to honor our duty to our patients and our profession. To compromise for anything less is unacceptable.