Imagine this. You tune in to the evening news and hear that a new virus has been discovered. What's more, it has infected over 80 million Americans. Is there good news? Just that most people don't know they have it, simply because they have no symptoms at all. On the other hand, this new virus will cause 300,000 precancerous conditions in women, and every year 31,000 men and women will develop one of six kinds of cancer caused by this infection. This year, next year and each one after.
I believe that mayhem would follow. And then a call that government and medical scientists DO something about it.
As it happens, this is not science fiction, except for the part about the virus being new. Rather, this is a description of the human papillomavirus, or HPV, discovered in 1956 and first linked to human cancers more than 30 years later. In 2006, a highly effective vaccine against HPV was licensed by the FDA. It was felt to be so important for cancer prevention that a year later the federal Centers for Disease Control and Prevention (whose Advisory Committee for Immunization Practices writes the national guidelines that undergird vaccine use in our country) called for the addition of HPV vaccine to the list of recommended childhood immunizations at the 11 or 12 year old visit.
Why are cervical cancer and other HPV malignancies still with us? For that matter, why is measles making a comeback after all these years? In the first instance, it is because uptake of the vaccine in the US has been unusually slow. In the latter, there is actual backsliding, with previously high rates of immunization eroding in pockets from New York to the Pacific northwest. Other countries, like Australia, are on track to completely eliminate HPV cancers in less than a decade. But not us. Why? It's not lack of access. In fact, in communities like ours across the country, those who a economically disadvantaged are MORE likely to be up to date with their immunizations, including these. Those at greater risk - for HPV, measles and other preventable infections - are the well off and the (otherwise) well educated.
Pediatricians like me approach the problem of immunization with great empathy for parents, who face a terrifying array of viewpoints in the marketplace of ideas. "Getting natural diseases is better than immunization." (This is such an odd idea. Behind my wife's ancestral, 19th century home in Riverhead there is a small, lovely graveyard. We walk there sometimes and linger at the tiniest tombstones, perhaps a dozen in all. They belong to those who did not survive infancy due to fatal infections like diphtheria and whooping cough that were once a commonplace in our towns.) "Vaccines overwhelm the immune system - especially when we keep adding new ones." (Children immunized now receive far FEWER antigens - the vaccine building blocks that create immunity - than they did in 1970, even after accounting for the longer list of conditions prevented. This is due to continuous improvement in vaccine design.)
"Vaccines cause autism." This deserves more space than we have here. In the 90s, concerns were raised about a widely used mercury preservative - the so-called smoking gun. Experts noted that the form of mercury was different from the biologically active kind that we should worry about. As a cautionary measure, the mercury was removed in 1999. However, the reported prevalence of autistic spectrum disorders did not decline thereafter - it increased. Then, in 1998, the Lancet published a paper by Wakefield et al describing 12 children with GI symptoms and autism following administration of MMR vaccine. At first thought to be provocative, and then just bad science, it was disclosed by 2010 to have been a conscious fraud, intended to support a malpractice claim by a UK firm. His medical license was revoked as a result. Since that time, 56 studies have been published internationally evaluating the hypothesis that vaccines are linked to neurodevelopmental conditions like autism, focusing on the MMR-autism issue and others. None of the 56 showed an association.
Let me be quite clear on one point. There are many controversies in Medicine - on diagnostic tests, on the best treatments for a host of conditions...but immunization is not one of those controversies. Among experts in pediatrics, infectious diseases and public health, the safe and effective vaccines listed by the ACIP and endorsed by the AAP and AAFP as recommended for all healthy children constitute a vital strategy for keeping our patients from harm.
Many have noted that new information is not of interest to those who are most staunchly opposed to childhood immunization, unless it reinforces their pre-existing bias - which is essentially the definition of a "cult." Where have we seen this before? This is a matter not for immunologists to decipher, but for social scientists. It is about an unravelling of trust - in doctors, in the methods and practitioners of science, and in the legitimate functions of governments in protecting the public welfare.
It is certainly about libertarianism, at least in some locales. Politicians have gone on record with the position that the science doesn't even matter. Instead, they argue, this is about the parent's right to be wrong.
Some feel that the most important contributor to skepticism is incomprehension. The notion that association between two events may not mean causality is just too abstract-sounding to be trustworthy, especially in an era when scientific literacy is in decline. Two decades ago, Cornell astrophysicist Carl Sagan expressed his serious concern that we were entering a new Dark Age. In his last book, "The Demon Haunted World - Science as a Candle in the Dark," this is what he said:
“I have a foreboding of an America in my children's or grandchildren's time when...people have lost the ability to set their own agendas or knowledgeably question those in authority; when, clutching our crystals and nervously consulting our horoscopes, our critical faculties in decline, unable to distinguish between what feels good and what's true, we slide, almost without noticing, back into superstition and darkness...
The dumbing down of America is most evident in the slow decay of substantive content in the enormously influential media, lowest common denominator programming, credulous presentations on pseudoscience and superstition, but especially a kind of celebration of ignorance...”
God save our children.
Here are a couple of items currently on my night table. I think they're worth buying. (Or stop by my office and I'll lend you a copy...IF you promise to give it back!)
Make It Stick: The Science of Successful Learning
Peter C. Brown, Henry L Roediger III, and Mark A McDaniel
Harvard University Press, 2014
I am a huge devotee of the counter-intuitive. During our resident teaching conferences I like to ask questions like this: “When evaluating a young child with fever of unknown source, should you be more reassured when Tylenol reduces the fever than when it doesn't ?” (The right answer, by the way, is “no”). Scientific investigations that merely confirm what most people would guess are rather boring, and generally speaking less than influential on clinical practice. It is the startling study result that grabs us.
In that spirit, Brown and colleagues have put together an engaging tour of learning theory. The sub-title could have been “Everything you thought you knew about learning is wrong.” Who would quibble with any of these truisms… that it is helpful to reread the textbook chapter (or your notes) before a test… that making learning easy and fun also makes it more effective…that when learning math, it’s best to really nail down one skill before moving onto the next….or that when memorizing, drilling the same material over and over is the ticket, because practice makes perfect?
According to the authors, each of these tropes is simply myth.
To the contrary, studies tell us that a state of moderate performance anxiety consolidates learning more effectively than a state of ease. This is why listening to a speaker from the back row of the lecture hall transfers far less information than case-based learning (and why “lecturing” is forbidden at the Zucker/Northwell School of Medicine). Additionally, education science tells us that while combining disparate skills in active problem solving may seem more chaotic than tackling one new discipline at a time (Anatomy, Physiology, Pharmacology), the former gets objectively better results including more retention of new knowledge and greater competence in applying that knowledge in context.
Among the tenets of education at Zucker is that “assessment drives learning.” In a sense, this is the counterpoint to those who oppose too much testing, complaining that it encourages “teaching to the test” and stifles creativity. Once again, the evidence says otherwise. In well-conducted comparative studies, students who were subjected to low stakes testing throughout a course (the pop quiz) ended up performing significantly better in the final exam than a comparison group whose experience was the same in all other respects.
The authors note that, when asked, even highly motivated students don’t necessarily prefer the more effective methodologies. It seem that introspection doesn’t always provide the best answers when it comes to our own psychology, which is to say that the Socratic maxim “know thyself” is easier said than done.
*********************************
Leaves of Grass
The First Edition - 1855
Walt Whitman
Barnes and Noble Books, 1997
A point of clarification. I’m not actually reading Leaves of Grass for the first time. Rather, I’ve never stopped reading it since I was 21 and took an upper level course in the American Transcendentalist movement focusing as one must on the works of Ralph Waldo Emerson (author of “Self-reliance” and so many other essays); Henry David Thoreau (“Walden”) and, of course, the greatest American poet of all time and self-stylized bard of the New World, Walt Whitman.
Pop quiz: how many collections of poems did Whitman write? Oddly, the answer is just one. This one. Leaves of Grass, first self-published in 1851, grew over four decades from a thin folio of a dozen poems to over 400. The first poem (in almost every sense) is “Song of Myself”. It is the gateway, not only to this organic collection, but to Walt Whitman, a mythologic figure wholly created by Walter Whitman: poet, Civil War orderly, newspaper publisher and (as all residents of our Town should be required to know) Huntingtonian. Beyond that, it is a gateway to the 19th century movement known as Transcendentalism.
When first published, Leaves of Grass drew little critical attention, except from those commentators who derided Whitman’s meandering style and loose poetical structures. Were it not for the fact that a copy arrived in the hands of the deeply respected Emerson, Whitman may never have achieved an audience. Most were nevertheless baffled by the elder’s effusive praise of the new poet and his claim that this was an original, authentic, sinewy and quintessentially American voice.
What were the Transcendentalists trying to say, exactly? Theirs was a protest movement, against European academics and tastes, against philosophies and aesthetic constructs that put Man at arm’s length from the natural world and from personal experience. Transcendentalism was an American romantic movement that eschewed “authority” in favor of personal connection with nature, and unmediated judgments of what is beautiful and good and true. It is no wonder then that Emerson was thunderstruck from the first lines of Whitman’s first work, “Song of Myself”…
I sing myself
And celebrate myself
And what I assume you shall assume,
For every atom belonging to me as good belongs to you.
I loafe and invite my soul,
I lean and loafe at my ease…observing a spear of summer grass.
In a world mediated not so much by academic authority or social convention as by Instagram and Twitter, the idea of stripping away the extraneous to achieve true communion, direct experience and self-knowledge seems as topical, and as attractive, as ever.
The deployment of initiatives under the banner of "antimicrobial stewardship" has been endorsed by an impressive array of organizations, including the American Academy of Pediatrics, American Society of Health-System Pharmacists, Infectious Diseases Society for Obstetrics and Gynecology, Pediatric Infectious Diseases Society, Society for Hospital Medicine, and the Society of Infectious Diseases Pharmacists. How could any thinking person be opposed? I'm not, actually. But here's where I think they may go wrong.
Hospital-based antimicrobial stewardship programs (ASPs) benchmark their success against two goals - cost reduction associated with decreased drug utilization, and, aspirationally at least (because it is a difficult outcome to measure) reduction in the spread of antibiotic resistance.
Both outcomes are consequential. At the institutional level, effective ASPs can save $200,000 - 900,000 annually, according to the IDSA. And antibiotic resistance is a problem of global proportions. In the US alone, over 2 million individuals are sickened by antibiotic-resistant infections and 23,000 die each year (CDC, 2013).
Here's the problem. Neither hospital cost savings nor the global threat of a "post-antibiotic era" are compelling to the practitioner at the bedside or in his examining room, whose only goal is to do the best, right thing for the patient in front of him. And these are the individuals, at the end of the day, whose decisions matter the most.
That's why, in putting together a conference for our Family Medicine residents on appropriate antimicrobial use in children, I didn't mention cost savings at all. It is also why I talked about the resistance problem not as a headline, but as a footnote. For the practitioner, it is most important to understand that the problem of antibiotic over-use is one that impacts each individual patient. Over-use errors, at bottom, are no different than other kinds of medical error. Though outcomes vary, we risk serious, avoidable harm to our patients. This is an issue not of economics but of standards-of-care and ethical practice. The message - once again - is primum non nocere.
Complications of Non-indicated Antibiotic Therapy
- Allergic reactions
- Stevens-Johnson Syndrome
- Toxic epidermal necrolysis
- Antibiotic associated diarrheal illness
- C. difficile colitis
- Alterations in the gut microbiome
- Obesity and Type 2 diabetes
- Others
Why do physicians make these errors?
The literature points to some common themes. In the February issue of the journal Pediatrics, Poole and colleagues report on antibiotic use in US emergency departments. While they find errors across the board, there is a clear disparity between treatment in pediatric EDs (those that treat mostly children) and general emergency rooms. The latter, being far more numerous, are the site of care for more than 80% of children seeking emergency treatment. The authors' conclusion is that more children receive antibiotics for conditions not warranting such treatment if they are seen in a non-pediatric ED. And when antibiotics are warranted, they are less likely to receive medication consistent with expert guidelines when seen in these "adult" EDs.
The authors go on to speculate that differences in training and experience fuel these disparities and others. This is not surprising. Previous studies have demonstrated similar differences in treatment for children with asthma, croup and head injury.
Nor is the knowledge problem limited to children and Emergency Departments. A Dutch study evaluating outpatient care by 84 general practitioners found that individual physicians over-treated at significantly different rates (Akkerman, 2005). Logistic regression analysis found that practitioners who had practiced longer AND scored poorly on a knowledge test about respiratory tract infections were most likely to over-prescribe when compared with their peers. Perceived time pressure and contact with pharmaceutical salesmen also increased risk.
As songwriter Todd Rundgren wrote, "Love is the answer." When it comes to avoiding errors of antibiotic overuse and avoidable harm to children, medical knowledge and keeping up to date with the literature seem to run a close second.
As it happens, this is not science fiction, except for the part about the virus being new. Rather, this is a description of the human papillomavirus, or HPV, discovered in 1956 and first linked to human cancers more than 30 years later. In 2006, a highly effective vaccine against HPV was licensed by the FDA. It was felt to be so important for cancer prevention that a year later the federal Centers for Disease Control and Prevention (whose Advisory Committee for Immunization Practices writes the national guidelines that undergird vaccine use in our country) called for the addition of HPV vaccine to the list of recommended childhood immunizations at the 11 or 12 year old visit. 
"Vaccines cause autism." This deserves more space than we have here. In the 90s, concerns were raised about a widely used mercury preservative - the so-called smoking gun. Experts noted that the form of mercury was different from the biologically active kind that we should worry about. As a cautionary measure, the mercury was removed in 1999. However, the reported prevalence of autistic spectrum disorders did not decline thereafter - it increased. Then, in 1998, the Lancet published a paper by Wakefield et al describing 12 children with GI symptoms and autism following administration of MMR vaccine. At first thought to be provocative, and then just bad science, it was disclosed by 2010 to have been a conscious fraud, intended to support a malpractice claim by a UK firm. His medical license was revoked as a result. Since that time, 56 studies have been published internationally evaluating the hypothesis that vaccines are linked to neurodevelopmental conditions like autism, focusing on the MMR-autism issue and others. None of the 56 showed an association. 
