In honor of my father

My relationship with my Dad was not the easiest: we were so alike that all of his flaws were magnified in my estimation and bugged me disproportionately. But it was not always this way. When I was a kid in Odessa, we were really close. He told me tall tales to get me to eat my dinner, he took me for walks, he told me stories about our city. He instilled his love of Odessa in me, a love which I had forgotten until just the last couple of weeks.

I finally went back to Odessa after a 35-year absence. Just thirteen when we left, I was a reluctant party to our emigration. Despite my resistance, once we came to the US, I assimilated most successfully and repressed every notion of being from Odessa -- accent, uniquely Odessit attitude toward life, everything. Until I went back 10 days ago.

I arrived on a plane from Istanbul on Wednesday morning. The airport is a tiny one-story building with an attached airfield. Its only concession to modernity is buses that cart passengers between the building and the aircrafts. Stepping out of the plane, I sensed something achingly familiar in the light, the smells and sounds of the city. And this sense was to persist through the three days that I spent there.

Odessa, known as the "Pearl of the Black Sea", is the ultimate planned city. Established by the order of Catherine the Great in 1794, its role was to be a door to the southern trade routes, leading easily to the Ottoman Empire, as well as the ports of Western Europe. The architecture of the city, its art and literature, reflect the liberal, permissive attitude fostered by its founding planners that made it a civic and commercial success prior to the October Revolution of 1917. Now, emerging from her 70-year repression, Odessa greeted me with open arms.

The love for the city I learned from my father permeates everything in Odessa: Odessits love their city, despite her myriad flaws and imperfections. In this they are not given to extremes of thinking her either perfect or abominable. Their attitude is one of reverence and understanding. Some of her streets are perfect, while others are at the edge of ruin, and she still smiles and winks to us knowing that she transcends these minor details.

I went to the most treasured of places in Odessa, the Opera Theater. I sat in the sixth row, close enough to smell the make up. It was Rigoletto, and as Gilda was singing her aria, I could feel my Dad next to me, nodding and humming along with the music, as he always used to do. And I finally understood his years of silent longing for this most unpretentiously beautiful of all cities I have ever been to. Because if you ever visit Odessa, it will happen to you too.

So, on this, my first Father's day without you, I give you my love for our beautiful city.

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Remember: Social media is social

A few days ago, several news outlets reported on Newt Gingrich's unfortunate turn of phrase about our President. In a speech in Georgia he referred to Obama as "the most successful food stamp president in modern American history." Promptly, David Gregory of NBC News called Newt on the potential racist connotations of this remark, thus precipitating a maelstrom of "liberal media" accusations from the usual suspects (here and here). And so it goes, possibly a careless figure of speech, possibly racially charged code, but everyone is now yelling and screaming about whether or not it was OK to say and subsequently to accuse.

There is a much bigger issue at stake than just the utterance of these words. While they offend me and make me think that they were spoken deliberately to elicit racial tensions, the point is that, in an obtuse sort of a way, they can be defended as non-racial in nature. Unfortunately, the speaker's intention is not the issue any longer, so much as the fact that these words can easily be construed as racially inciting by large swathes of the population. And this is an important point: once squeezed out, much like the toothpaste from its tube, these words cannot be forced back. They will exist in perpetuity and continue to elicit visceral reactions.

Such is the nature of public discourse. Which brings me to the discussion on Bryan Vartabedian's site about the etiquette of healthcare professionals on Twitter. The example of the particular Twitter stream from a healthcare professional who tweets anonymously under a nom de plume, precipitated a spirited discussion (see over 100 comments) about the propriety and professionalism of her messages in this public forum. While many saw her behavior as at the very least undesirable, some MDs and, more concerning, medical students, did not see a thing wrong with her eructations. Furthermore, she responded via Twitter that she was quite surprised by this tongue lashing and did not know what was so offensive in her messages.

But that is just it! Enough readers saw her words as being disrespectful and even contemptuous of patients, regardless of her intent. And this is the crux of the matter: the distance between the output, and its intent, and its interpretation by the listener or reader can be vast, especially when the message is reduced to 140-character snippets. This is why when people lament that communication is the biggest obstacle in all human relations, they are right. And different types of communication deserve different levels of scrutiny.

So, here is my bottom line. Whether we intend to be hurtful or disrespectful in our tweets or racially divisive, as in our political discourse, is immaterial. In an open forum, if we are concerned with being empathic and careful of others' feelings, we should think twice (or more) about what we put out there. Because extending this blogger's thought to all communications, Twitter, like a tattoo, is forever. And everyone is looking.  

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All harm and no benefit: Wake up and smell the pus!

Ideas are a little bit like a pimple: There needs to be enough pressure that builds up to cause one to erupt into consciousness. So it has been with my thinking around value of certain consumables. And the more I think about it, the more I am convinced that the law of diminishing returns is scowling at us from its perch. Here are 3 examples that I hope will drive this point home.

Take cigarettes. They cost money to manufacture, they cost a boat load of money to buy, yet what do they produce that is of value? A rise in the teen's coolness quotient? A brief relaxation effect? Appetite control? Sultriness? A tax base? All of this is so squashed by the sheer size of the risk of disease and death that cigarettes cause as to make any of these potentially perceived "benefits" infinitesimally small, thus bringing the harm in the harm-benefit ratio into the range of infinity. So, huge investment, personal and societal, for a negative return.

Next comes food. I am sorry, but I am going to stop wringing hands and apologizing for being convinced that there is in fact unequivocal scientific proof (yes, I did say "scientific proof") that our gargantuan and infinitely dysfunctional food production system is poisoning our public. Obesity is but one manifestation of this diseased production. The potentially more catastrophic consequences include accelerated deforestation with the consequent extinctions and climate change, which is rapidly moving from the realm of abstract future into the concrete present. Many have written about the science behind all this, and I will not belabor it here. Yet it is clear that this is another example of ever-increasing investment and subsidies made at the peril of environmental and public health. So, again, we have a cigarette-like situation, where the numerator of harm overwhelms the denominator of benefit to such and absurd degree that it threatens to stamp us out, like a drunken Godzilla strolling down a city street, pulverizing everything to dust.

And of course, we must bring in "healthcare." I put it in quotes because there is so little health in this healthcare paradigm. It is striking to me how the "prevention" conversation has been hijacked by the vocabulary of "screening." And don't you practically feel like a criminal refusing some screening test or another, or worse yet, refusing to comply with your annual check-up? At the same time, every day we hear about harm due to overzealous search for what is wrong with us. Healthy people walk into a place of "healthcare" delivery and walk out at best with a handful of pills and a bunch of ICD-9 codes attached to them, or at worst end up dead (or so close to it that they wish the job had been completed). I am sure you all remember the paper in the Archives of Internal Medicine that precipitated this post, where a healthy woman ended up needing a heart transplant because of the dogged search for a diagnosis that did not exist. More recently, several lay press articles, including this one, have highlighted data on an increase in potentially life-threatening post-biopsy infections among men undergoing a prostate biopsy. And the kicker is that the PSA test, which is what usually leads to a biopsy, has been so convincingly characterized as completely unreliable that it is difficult to believe that anyone still submits himself to it. And to top it all off, Archives of Internal Medicine has just published this paper on screening for heart disease in asymptomatic people (this means schmos like you and I who hang out in our offices without any heart symptoms). And, not surprisingly, they found an increase in the diagnosis and treatment of heart disease among those screened compared to those not screened, and absolutely no impact on the outcomes! All harm or potential harm and no benefit! We should be outraged, but instead we demand more intervention.

Given our peaceful acceptance of pushing (yes, pushing) harmful stuff on the public without any pretense at benefit, just as the brazen strategies of the tobacco and monocultured foods have done for so long, it is not surprising that we are willing to dive head first into this quicksand of harm. It attests to how effective the PR industry's brainwashing is. But really, isn't it time to wake up and smell the pus?      

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In praise of not knowing

Recently I had the occasion to tell my 10-year old an old secret: until I was into my forties, I had a strong belief that the rest of the people in the world knew something I did not know. I don't mean just about stuff I do not know, but about everything! It was unnerving, anxiety-provoking and self-defeating. Until one day I had the epiphany that most humans feel this way, not just me. So, be humbled by not knowing and move on.

Yet even more recently this line of self-examination has led me to the conclusion that I end up saying "I don't know" a lot. I read a definitive tweet from someone I respect, and I say to myself "I don't know"; I read a new paper in a journal and say, "Gee, I don't know", I hear a political speech, and I walk away saying, "I just don't know." Is it that I am an idiot, or intellectually lazy? Perhaps. But what is occurring to me more and more lately is that what we are convinced of today will be much less certain and obvious tomorrow, barring some truly sacred cows. This is called growth, and as far as I can tell is a desirable development.

On the other hand, saying "I don't know" sometimes means that it just does not make sense to take sides. I know that we have to apply current knowledge and not wait for perfect information, but I still do not see getting all polar about stuff. Most of the time we act like there are only two possibilities, and they are diametrically opposed to one another. Well these are false dichotomies promoted by our educational system, which drills into us the idea that there are only two answers to any question: the right one and the wrong one. What if this is untrue? What if we change the way we think about the world, and instead of seeing only the black and the white, the left and the right, the correct and the incorrect, we start really seeing the entire continuum of possibilities? What a fantastic variety of solutions we might stumble upon to our perennial questions!

A nice mind game could be trying to think about stuff without using words. Can we do that? It is thoroughly difficult, yet it is language that seems to bracket our conceptual understanding of the world within and around us. Take the word "race" or "gender", for example. These are human-made and defined terms, which are meant to distinguish rather than merge. Yet just think how uncomfortable we can be made by a person with an ambiguous gender identity, say. Why? Because he/she does not fit into our preconceived dichotomy? Uncertainty is uncomfortable, and dichotomies cure uncertainty. But I am not sure that nature is all that into dichotomies.

The human brain is wired for "belonging." I believe it is for this reason we gravitate to our respective extreme corners of thinking and being, instead of meeting somewhere in the isle. The isle is an uncomfortable place, yet that is where we must aim to be. All the borders we have created are imaginary separations. Instead we can reposition them as the glue that unifies that which lies to either side.

Here is to not knowing more!

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Of pigs, Babel and totalitarianism

Here is a weird thought: Our current food production is closer to the Soviet collectivization than to the free enterprise model. Outrageous? Not really.

I had avery interesting weekend. As some of you may know, I am finally going back to Odessa (no, not the one in Texas) after a 35-year hiatus -- we left when I was 13. Since I am only spending 3 days there, I have been doing a lot of soul-searching to figure out what I need to get out of the trip. Serendipity struck last Sunday, when in the midst of a gloomy morning I went online to search for something to do in the Valley, indoors, and came upon this. Now, although most of you probably have never heard of Babel, he was a very well known and respected author of the Soviet era. A Jew in peri-revolutionary Odessa, he was a master story teller, best known as the bard of the colorful life of the Moldavanka, a district of Odessa particularly rich in poverty and Jewish gangsters. My father was a great scholar of Babel, and I remember hearing his stories from a very young age. I also remember passing by his house in the streets of Odessa, with a modest plaque marking its historic lineage.

But Babel became personal for me when in 1996 my parents brought me a gift from their trip to our home town, a book of Babel's short stories with an inscription from my cousin's family. This inscription pointed me specifically to page 19 of the tome. As my eyes focused on the small print, and as I started to skim the text, I shortly came upon the following sentence: "None other than Dr. Zilberberg operated on him..." Yes, my great-grandfather was a fairly well respected surgeon in Odessa at the turn of the 20th century, and Babel in fact mentions him in several other of his works, including this autobiographical sketch. Unfortunately, most of what I know about that Dr. Zilberberg has been passed down through the idealized prism of the family lore. Yet I am thoroughly intrigued by the claims that his professional ethics forbade him from turning anyone away, and he cared for the rich Jewish ladies alongside the mafiosi of Moldavanka with the same level of professionalism. And for this, the legendary gang leader Mishka Japonchik, who incidentally is rumored to be related to me on my mother's side, but that is a story for a different time, is known to have afforded him protection from the rogue elements of his gang. The story is well told by my father in this essay, albeit in Russian.

But I digress. So I immediately got myself out the door to get to the program and sat, along with about 100 other attendees, riveted by Andrei's reading of his grandfather's work. After the intermission he read the story that features my great-grandfather, and of course in the Q&A I came out as the great-granddaughter of the great surgeon. Because of this I was invited to join a group of locals and Andrei for a memorable dinner. It was at this dinner that an insightful comment from the brilliant hostess clarified the mindset for my trip. And it was at this dinner that Andrei started to remind us about his grandfather's journalistic work about the collectivization movement in the nascent Soviet Union. It is at this dinner that I got a very clear picture of how our current food production is eerily totalitarian. Imagine if you will being a small farmer at the turn of the 20th century in Russia. You are by no means well off, and all you have is the land and what it gives you after hours and hours and hours of backbreaking loving tending. Imagine now that in comes a new regime, claiming to be for the workers and peasants, and now considers you a land-owner, a kulak, a member of the bourgeoisie, and takes away your farm (the term used is "raskulachit'" or de-kulakize) and puts it in the hands of the collective. Now the big whole owns your meager part and you are left with nothing.

Now let us think about what has transpired in the US over the last century. Let us look at the meat industry specifically. Its deplorable practices at the turn of the 20th century were chronicled brilliantly by Upton Sinclair, and I will only mention that, according to Eric Schlosser's writing, in 1917, 5 largest meatpacking companies owned 55% of the market. On the heels of Sinclair's book, and prompted by the appalling confirmation by the government investigation of Sinclair's claims, the government embarked on a regulatory voyage culminating in the 1920s with the anti-trust legislation, meant to ensure that no monopoly (or oligopoly) would control any market in our nation, thus precluding companies from getting big enough to control our free markets. Well the result of this was a sharp decline in the market share for each of the giants. Yet this was transient, and, as Schlosser points out on page 162, today the top 4 meatpacking giants control over 80% of the market. What happened? Well, we call it "deregulation." But is it really all that different from collectivization? Not that much -- it is still the few controlling the many, and the many going bankrupt and having no leverage to improve their lot. But, you say, it is not the government, but private interests that are at play, so this makes it all better, right? Well, are you sure about that? Who is pilling the strings of our congressional representatives? And these strings are only going to get stronger, thanks to Citizen's United decision from the Supremes. So, while the politicians are foaming at the mouth calling Obama a socialist and a communist, we are careening head first away from democracy and into that social structure we contemptuously call totalitarianism.

Simplistic? I don't think so. Think about it: a pig with lipstick on is still a pig.    

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When do diagnostic tests improve mortality?

I thought this post, originally published last May, was worth revisiting apropos this paper that came out in this week's Archives of Internal Medicine. Below I discuss some of the data in the paper, as they were presented in an abstract at a meeting last year, as the context for understanding various mortality statistics. 

The question the title of this post poses is well worth asking, particularly as we argue about the merits of mammography screening. The USPSTF has really stirred up the hornet's nest with this one, and the politicians cannot help but get on their populist pulpit, ignoring the facts completely. Oh well, what else is new?

But the question remains: do screening or diagnostic tests that are more sensitive save lives? A great talk on pulmonary embolism detection and outcomes by a recent graduate from the Dartmouth group at the American Thoracic Society last week prompted me to clarify this. We all hear that mortality from many diseases has decreased over the last few decades. But is this true? In order to answer this question, one has to ask what is meant by mortality. Even people well versed in epidemiology and biostatistics occasionally blur the lines between mortality and case fatality, and to our question the distinction is critical. Case fatality is defined as the proportion of patients with the disease that dies, while mortality is a population-based measure, a proportion of all of the population at risk for the disease that dies. The difference lies in our old friend the denominator, which will always keep us honest.

Let's go through a simple example to illustrate this concept. Let's pretend that the total number of cases of disease D diagnosed using stone-age test T 30 years ago was 100 in a population of 10,000 people. Of these cases, 90 died, giving us the case fatality of 90% and mortality of 9 per 1,000 population. Now, we have a new test for D, a super-Doppler-MRI-PET-cyberscan called über-T, a much more sensitive test than the old "gold standard" test T. And now we detect 1,000 cases of D in the population of 10,000 people. Of the 1,000 cases detected by über-T, 90 have died. The case fatality now has decreased dramatically from 90% to 9%, and we can pat ourselves on the back for a job well done, right? Not so fast, the population mortality from disease D has remained a steady 9 per 1,000 population!

So, what does this mean? Does it mean that über-T, which costs 2 orders of magnitude more than its predecessor, is worthless? Well, decide for yourselves. What it means to me is that the additional cases detected by über-T, though finding earlier stage disease, thus increasing the denominator for the case-fatality calculation, has had no impact on the numerator and therefore has not in fact improved the only mortality that matters: population mortality related to the disease.

So, next time a politician tells you how well we are doing with technological innovation in disease management, ask this simple question: Has all the money and innovation really altered the important outcomes, or is this all smoke in mirrors, a mirage created by our irrational belief that technology is our salvation? This may be an uncomfortable epiphany for some. But think about the 900 excess cases of the pseudo-disease diagnosed in our example above -- how many people could have been saved becoming a chronically ill person, how many complications of follow-up procedures could have been avoided, and yes, how much money could have been spent on something other than healthcare? And asking these questions may help us to identify technological advances that actually improve our lives, as opposed to those that merely create attractive business opportunities and stimulate the economy.            

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How many diseases does it take?

It is not a secret that I dislike tobacco companies. Intensely. I do not see the point of allowing them to sell a product whose value is all in the negative. I am appalled that we are looking for expensive ways to diminish lung cancer mortality before considering a complete ban on this disease promotion apparatus. Yet this story in the LA Times got my goat. Briefly, a woman who has smoked for years and has had smoking-related obstructive lung disease since 1989 decided to sue tobacco companies after developing lung cancer in 2003. The suit has been making the rounds in various levels of courts, since the defendants asserted that she had exceeded the 2-year statute of limitations following the onset of her smoking-caused disease, referring to the 1989 COPD diagnosis. However, the California State Supreme Court has ruled that she can still sue the manufacturers, since she filed her suit within two years of the lung cancer diagnosis. So, why am I bothered?

Well, here is the thing: once you develop lung disease, followed by periodontal disease, as this woman did, had she really remained unaware that cigarettes are bad? That they cause problems? Is it really possible to live in our world and NOT be aware that tobacco kills? And if she was aware and continued to smoke, whose responsibility is it that she developed lung cancer, hers or the manufacturer's? Well, you say, but the tobacco companies are unethical and lied about making cigarettes more addictive by adding undisclosed ingredients. So, how are we, the consumers, to know? Well, this is pretty simple: We have free will, don't we? And if you have the free will, you have to exercise some will power, no? Is this not what the human condition is all about? Consider what would happen if we just let all of our desires run rampant. At the simplest level, who would want to get up early and do back-breaking work to produce food for our communities? And why contain anger at town hall meetings, when my humanity tells me to get into a brawl? These are basic ways in which we conquer our instincts and do what we need to do to live in a society with human beings and other organisms. But what is peculiar is that we have not extended these exercises of will to the area of consumerism. In other words, it seems to me that whichever way the market, and more importantly marketing, goes, so goes the perceived need for personal will and responsibility. Ergo, smoking despite warnings of its dire effects is OK, since the poor soul is addicted, and she can always sue on the back end, while the murderous tobacco CEOs and investors walk away with the profits. I don't know, I think it is embarrassing to give up your will that way personally.

There are two nuances to this view that I want to express. First, I do believe that cigarette companies are unethical, cruel and in debt to us, but the debt that needs to be paid is to the society, not to individuals. It is a debt to our public health that requires complete withdrawal of their product from the market and a large monetary compensation to promote healthy habits among human beings. Second, I believe that there are shades of this personal vs. societal responsibility balance that are important. Take, for example, food options for an inner city youth who lives in poverty. He may want to exercise his free will to get better nutrition than a $1.25 meal at McDonald's offers, or spend his $1.25 on an apple instead of a bag of potato chips, but for this he has to go across town, a trip that he does not have the means to undertake. This, folks, is where this young man's personal responsibility needs to be supplemented with societal commitment to equity.

So, should this unfortunate smoker with severe and life-threatening sequelae of tobacco abuse be able to sue the producer of the poison, even if she knowingly took the poison? I guess as a society we have decided that this is OK, but as an individual I am dubious. Yet it really is in the interest of our common health and wealth to punish and eliminate producers of such poisons as a society. Relying on individuals to do this job is just a perpetuation of the idea that we are not responsible for our actions. And furthermore, this becomes but a small pimple on this giant's ass, a nuisance, and not a necrotizing fasciitis that is required to kill it once and for all. 

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Invalidated Results Watch, Ivan?

My friend Ivan Oransky runs a highly successful blog called Retraction Watch; if you have not yet discovered it, you should! In it he and his colleague Adam Marcus document (with shocking regularity) retractions of scientific papers. While most of the studies are from the bench setting, some are in the clinical arena. One of the questions they have raised is what should happen with citations of these retracted studies by other researchers? How do we deal with this proliferation of oftentimes fraudulent and occasionally simply mistaken data?

A more subtle but no less difficult conundrum arises when papers cited are recognized to be of poor quality, yet they are used to develop defense for one's theses. The latest case in point comes from the paper I discussed at length yesterday, describing the success of the Keystone VAP prevention initiative. And even though I am very critical of the data, I do not mean to single out these particular researchers. In fact, because I am intimately familiar with the literature in this area, I can judge what is being cited. I have seen similar transgressions from other authors, and I am sure that they are ubiquitous. But let me be specific.

In the Methods section on page 306, the investigators lay out the rationale for their approach (bundles) by stating that the "ventilator care bundle has been an effective strategy to reduce VAP..." As supporting evidence they cite references #16-19. Well, it just so happens that these are the references that yours truly had included in her systematic review of the VAP bundle studies, and the conclusions of that review are largely summarized here. I hope that you will forgive me for citing myself again:

A systematic approach to understanding this research revealed multiple shortcomings. First, since all of the papers reported positive results and none reported negative ones, there is a potential for publication bias. For example, a recent story in a non-peer-reviewed trade publication questioned the effectiveness of bundle implementation in a trauma ICU, where the VAP rate actually increased directionally from 10 cases per 1,000 MV days in the period before to 11.9 cases per 1,000 MV days in the period after implementation of the bundle (24). This was in contradistinction to the medical ICU in the same institution, which achieved a reduction from 7.8 to 2.0 cases per 1,000 MV days with the same intervention (24). Since the results did not appear in a peer-reviewed form, it is difficult to judge the quality or significance of these data; however, the report does highlight the need for further investigation, particularly focusing on groups at heightened risk for VAP, such as trauma and neurological critically ill (25).             

Second, each of the four reported studies suffers from a great potential for selection bias, which was likely present in the way VAP was diagnosed. Since all of the studies were naturalistic and none was blinded, and since all of the participants were aware of the overarching purpose of the intervention, the diagnostic accuracy of VAP may have been different before as compared to after the intervention. This concern is heightened by the fact that only one study reports employing the same team approach to VAP identification in the two periods compared (23). In other studies, although all used the CDC-NNIS VAP definition, there was either no reporting of or heterogeneity in the personnel and methods of applying these definitions. Given the likely pressure to show measurable improvement to the management, it is possible that VAP classification suffered from a bias. 

Third, although interventional in nature, naturalistic quality improvement studies can suffer from confounding much in the same way that observational epidemiologic studies do. Since none of the studies addressed issues related to case mix, seasonal variations, secular trends in VAP, and since in each of the studies adjunct measures were employed to prevent VAP, there is a strong possibility that some or all of these factors, if examined, would alter the strength of the association between the bundle intervention and VAP development. Additional components that may have played a role in the success of any intervention are the size and academic affiliation of the hospital. In a study of interventions aimed at reducing the risk of CRBSI, Pronovost et al. found that smaller institutions had a greater magnitude of success with the intervention than their larger counterparts (26). Similarly, in a study looking at an educational program to reduce the risk of VAP, investigators found that community hospital staff were less likely to complete the educational module than the staff at an academic institution; in turn, the rate of VAP was correlated with the completion of the educational program (27). Finally, although two of the studies included in this review represent data from over 20 ICUs each (20, 22), the generalizability of the findings in each remains in question. For example, the study by Unahalekhaka and colleagues was performed in the institutions in Thailand, where patient mix and the systems of care for the critically ill may differ dramatically from those in the US and other countries in the developed world (22). On the other hand, while the study by Resar and coworkers represents a cross section of institutions within the US and Canada, no descriptions are given of the particular ICUs with respect to the structure and size of their institutions, patient mix or ICU care model (e.g., open vs. closed; intensivists present vs. intensivists absent, etc.) (20). This aggregate presentation of the results gives one little room to judge what settings may benefit most and least from the described interventions. The third study includes data from only two small ICUs in two community institutions in the US (21), while the remaining study represents a single ICU in a community hospital where ICU patients are not cared for by an intensivist (23).  Since it is acknowledged that a dedicated intensivist model leads to improved ICU outcomes (28, 29), the latter study has limited usefulness to institutions that have a more rigorous ICU care model.

OK, you say, maybe the investigators did not buy into my questions about the validity of the "findings." Maybe not, but evidence suggests otherwise. In the Discussion section on page 311 they actually say

While the bundle has been published as an effective strategy for VAP prevention and is advocated by national organizations, there is significant concern about its internal validity.

And guess what they cite? Yup, you guessed it, the paper excerpted above. So, to me it feels like they are trying to have it both ways -- the evidence FOR implementing the bundle is the same evidence AGAINST its internal validity. Much like Bertrand Russell, I am not that great at dealing with paradoxes. Will this contradiction persist in our psyche, or will sense prevail? Perhaps Ivan and Adam need to start a new blog: Invalidated Results Watch. Oh? Did you say that peer review is supposed to be the answer to this? Right.  

    

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Another swing at the windmill of VAP

Sorry, folks, but I have been so swamped with work that I have been unable to produce anything cogent here. I see today as a gift day, as my plans to travel to SHEA were foiled by mother nature's sense of humor. So, here I am trying to catch up on some reading and writing before the next big thing. To be sure, I have not been wasting time, but have completed some rather interesting analyses and ruminations, which, if I am lucky, I will be able to share with you in a few weeks.

Anyhow, I am finally taking a very close look at the much touted Keystone VAP prevention study. I have written quite a bit about VAP prevention here, and my diatribes about the value proposition of "evidence" in this area are well known and tiresome to my reader by now. Yet, I must dissect the most recent installment in this fallacy-laden field, where random chance occurrences and willful reclassifications are deemed causal of dramatic performance improvements.

So, the paper. Here is the link to the abstract, and if you subscribe to the journal, you can read the whole study. But fear not, I will describe it to you in detail.

In its design it was quite similar to the central line-associated blood stream infection prevention study published in the New England Journal in 2006, and similarly the sample frame included Keystone ICUs in Michigan. Now, recall that the reason this demonstration project happened in Michigan is because of their astronomical healthcare-associated infection (HAI) rates. Just to digress briefly, I am sure you have all heard of MRSA; but have you heard of VRSA? VRSA stands for vancomycin-resistant Staphylococcus aureus, MRSA's even more troubling cousin, vancomycin being a drug that MRSA is susceptible to. Now, thankfully, VRSA has not yet emerged as an endemic phenomenon, but of the handful of cases of this virtually untreatable scourge that has been reported, Michigan has had plurality of them. So, you get the picture: Michigan is an outlier (and not in the desirable direction) when it comes to HAIs.

Why is it important to remember Michigan's outlier status? Because of the deceptively simple yet devilishly confounding concept of regression to the mean. The idea is that in an outlier situation, at least some of the effect is due to random luck. Therefore, if the performance of an extreme outlier is measured twice, the second time it will be closer to the population mean just by pure luck alone. But I do not want to get too deeply into this somewhat muddy concept right now -- I will reserve a longer discussion of it for another post. For now I would like to focus on some of the more tangible aspects of the study. As usual, two or three features of the study design reduce substantially the likelihood that the causal inference is correct.

First feature is the training period. Prior to the implementation of the protocol, which by the way consisted of the famous VAP bundle, which we have discussed on this blog ad nauseam, there was intensive educational training of the personnel on a "culture of change", as well as the proper definitions of the interventions and outcomes. It is at this time that the "trained hospital infection prevention personnel" were intimately focused on the definition of VAP that they were using. And even though the protocol states that the surveillance definition of VAP would not change throughout the study period, what are the chances that this intensified education and emphasis did not alter at least some of the classification practices?

Skeptical? Good. Here is another piece of evidence supporting my stance. A study from Michael Klompas from Harvard examined inte-rater variability in the assessment of VAP looking at the same surveillance definition applied in the Keystone (and many other) study. Here is what he wrote:

Three infection control personnel assessing 50 patients for VAP disagreed on 38% of patients and reported an almost 2-fold variation in the total number of patients with VAP. Agreement was similarly limited for component criteria of the CDC VAP definition (radiographic infiltrates, fever, abnormal leukocyte count, purulent sputum, and worsening gas exchange) as well as on final determination of whether VAP was present or absent.

And here is his conclusion:

High interobserver variability in the determination of VAP renders meaningful comparison of VAP rates between institutions and within a single institution with multiple observers questionable. More objective measures of ventilator-associated complication rates are needed to facilitate benchmarking and quality improvement efforts. 

Yet, the Keystone team writes this in their Methods section:

Using infection preventionists minimized the potential for diagnosis bias because they are trained to conduct surveillance for VAP and other healthcare-associated infections by using standardized definitions and methods provided by the CDC in its National Healthcare Safety Network (NHSN).

Really? Am I cynical to invoke circular reasoning here? Have I convinced you yet that CAP diagnosis is a moving target? And as such it can be moved by cognitive biases, such as the one introduced by the pre-implementation training of study personnel? No? OK, consider this additional piece from the Keystone study. The investigators state that "teams were instructed to submit at least 3 months of baseline VAP data." What they do not state is whether this was a retrospective collection or a prospective one, and this matters a little. First, retrospective reporting in this case would be a lot more representative of what has been, since these rates of VAP are already recorded for posterity and cannot presumably be altered. On the other hand, if the reporting is prospective, I can still conceive of ways to introduce a bias into this baseline measure. Imagine, if you will, that you are employed by a hospital that is under scrutiny for a particular transgression, and that you know the hospital will look bad if you do not demonstrate improvement following a very popular and "common-sense" intervention. Might you be a tad more liberal with identifying these transgressive episodes in your baseline period that after the intervention has been instituted? This is a subtle, yet all too real conflict of interest, which, as we know so well, can introduce a substantial bias into any study. Still don's believe me? OK, come to my office after school and we will discuss. In the meantime, let's move on.

The next nugget is in the graph in Figure 1, where VAP trends over the pre-specified time periods are plotted (you can find the identical graph in this presentation on slide #20). Look at the mean, rather than the median line. (The reason I want you to look at the mean is that the median is zero, and therefore not credible. Additionally, if we want to assess the overall impact of the intervention, we need to be embracing the outliers, which the median ignores). What is tremendously interesting to me is that there is a precipitous drop in VAP during the period called "intervention", followed by much smaller fluctuations around the new mean across the subsequent time periods. This to me confirms the high probability of reclassification (and Hawthorne effect), rather than an actual improvement in VAP rates, as the cause of the drop.

Another piece of data makes me think that it was not the bundle that "did it." Figure 2 in the paper depicts the rates of compliance with all 5 of the bundle components in the corresponding time periods. Again, here as in the VAP rates graph, the greatest jump in adherence to all 5 strategies is observed in the intervention period. However, there is still a substantial linear increase in this metric between the intervention period and through to 25-27 months period. Yet, looking back at the VAP data, no such robust commensurate reduction is observed. While this is somewhat circumstantial, it makes me that much more wary of trusting this study.

So, does this study add anything to our understanding of what bundles do for VAP prevention? I would say not, and it actually muddies the waters. What would have been helpful to see is whether any of the downstream outcomes, such as antibiotics administration, time on the ventilator and length of stay were impacted. Without impacting these outcomes, our efforts are Quixotic, merely swinging at windmills, mistaking them for a real threat.

       

          

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Is this double dipping? A new bipartisan House bill on oncology reimbursements

Here is another gem from the House of Representatives: a bipartisan bill to increase Medicare reimbursements to community oncology practices. While at first glance this seems like a reasonable idea, this detail is puzzling:

The so-called "prompt pay" legislation excludes certain discounts extended to wholesalers when calculating Medicare reimbursements and is strongly supported by oncologists.

Confused? Met too. Here is how I understand it. Many community oncology practices have set up infusion clinics, where they administer intravenous chemotherapy on site to their patients. To stock these infusion centers they deal with drug manufacturers and distributors to purchase the drugs at wholesale prices. The bigger the buy, the bigger the manufacturer discount. To the best of my knowledge these discounts are proprietary information, guarded like state secrets. Yet despite these discounts, the clinics charge Medicare a premium for the drugs themselves as well as for the service of administering. The way this legislation looks to me is that it will completely eliminate any reduction in reimbursement related to these discounts. Double dipping, anyone?

Now, I have many friends who are oncologists, and this is really not a slur against them. But these infusion clinics have always represented a cash cow for these practices. And who would not want to have a steady source of income to maintain a robust practice and have some money left over for a life? Again, this is not an indictment of community oncology practices. If, however, one takes an external perspective, this bill becomes something of an anathema to improving efficiency of healthcare delivery. If the reimbursement rates for administering these already exorbitantly expensive drugs improve further, will it not become even more difficult for an oncologist to tread the fine line of the conflict of interest between treatment only when it is in the patient's best interest and treatment for income optimization? Again, I want to point out that I am not singling out oncologists, as it is a part of the human condition to rationalize our selfish decisions by putting them in an altruistic light. And given the amount of uncertainty about who might respond to these drugs, it is easy to convince oneself that a trial of a therapy may be a reasonable idea, with the reimbursements providing a nudge in that direction.

A couple of quotes from the sponsors of the legislation are also worth reprinting:

"On any legislation today, you have to find a way to pay for it. And like any legislation, that's an issue with this one," Whitefield said. 

"But to be truthful, because of the oncologist groups and patient groups and others, we think that there may be some provisions in the healthcare bill that passed last year that we may be able to utilize some of those funds for this. All of it's about healthcare, and if we can convince people that this is more important than the others then we can do it."     

On any legislation today? You mean it has not always been like this? I guess we have all gotten used to credit as a life style, and now it is time to pay the piper.

Now, what about this: "Because of the oncologist groups and patients groups and others..."? Are they saying what I think they are saying? That because groups are likely to benefit are saying that this is vital, it is in fact vital? I also have to wonder who those "others" are. Hmmm, I wonder...

And this: "All of it's about healthcare, and if we can convince people that this is more important than others then we can do this." OK, so the statement is so grammatically abominable and non-sensical that I can interpret it any way I like. And it seems to me that they are implying that increasing these already hefty reimbursements is more important than stuff like paying for prenatal care and immunizations to the poor? And other essential services to the Medicare population? Well, if this is not the a poster child for why we need to be articulating the value of healthcare, I do not know what is.  

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Why easy is not always good

My mother-in-law is a typesetter. She will not read a book unless it is not only appealing in its content, but also pleasing to the eye. When I was in medical school, she did quite a bit of work for medical textbook publishers. Comparing books typeset by her to what I was grinding through on a daily (and nightly basis) incensed her: unwieldy tables appearing three pages away from the corresponding text, small letters crammed to capacity onto oversized pages, few illustrations -- all baffling, annoying (and easily fixable) transgressions against readability. Yet, like all budding docs of all generations, I plowed through these morasses of knowledge without giving its readability much thought -- this was just what you did to get to your goal.

Yesterday I was listening to a program where the author Amy Chua was interviewed about her (ahem) embattled autobiography Battle Hymn of the Tiger Mother. Ms. Chua, though evenly humored throughout the interview, was on the defensive nearly the entire time, explaining how the intent of her opus has been grossly misunderstood by the public, thanks to attacks by critics on her parenting style. And granted, looking at the book as a parenting manual through the prism of our Western parenting norms is a bit disturbing. Yet putting its events in a culturally appropriate context, as well as looking at the content as a narrative rather than a guide, leads to completely different conclusions.

Why am I bringing up Amy Chua's interview after talking about my conquest of the unreadable? Well, it seems that ease is what we have come to expect from everything. What I mean by this is that not only do we expect easily readable texts, but we also expect people to present themselves in such a way as to make it easy for us to like them. Why else change your appearance through life-threatening eating disorders and grueling surgeries, get coached on how to make friends and influence people, and comment on how unlikable some of our female politicians are? Is this not a triumph of form over substance?

Amy Chua clearly bucks this trend in her book and is paying the price. But what worries me is that we are all paying a price. By creating another false dichotomy of "she is nice" or "he is nasty", we have eschewed a more realistic view of our human foibles. We are all nice sometimes and nasty at others. Yet this dichotomy has proven supremely fruitful to our political discourse, where for 30 years this new reality has been taking root. And it has born fruit, so that now people who do not hold similar opinions to ours are summarily dismissed as "nasty" or idiotic, and we are satisfied to surround ourselves with "nice" like-minded sycophants. How primitive it renders our political and social interactions!

Ms. Chua's immigrant parents' philosophy resonated with my upbringing. Coming from lands of uncertainty and deprivation, as immigrants, our parents subscribed to Maslow's pyramid and taught us that economic security trumped everything else. This is why only certain career choices were acceptable, while others were relegated to the back burner of a hobby. These choices were not about ease, but about doing what we were taught was the right thing. As John Adams said:

I must study Politicks and War that my sons may have liberty to study Mathematicks and Philosophy. My sons ought to study Mathematicks and Philosophy, Geography, natural History, Naval Architecture, navigation, Commerce, and Agriculture, in order to give their Children a right to study Painting, Poetry, Musick, Architecture, Statuary, Tapestry, and Porcelaine.

We all set priorities, and some of them may not be easy. I myself still read books even if they are not all that well presented; my priorities are content and writing style, though, to be sure, I do not frown upon the beauty of the visual form. I even enjoy characters who in, their multidimensionality, are a challenge to like. And I have learned in the rest of my life to enjoy people who do not necessarily hold easy or quick appeal for me, yet in the long run prove to add unimaginable richness to my life. Nietzsche coined the famous quote "What does not break you will make you stronger." In all aspects of our lives, while, based on Nietzsche's statement, adversity is a sufficient but not necessary road to strength, pushing ourselves a little bit out of our stuporous ease may prove to be one timely remedy.

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The value of a test

Reading this vintage paper on C diff from the Archives of Pediatric and Adolescent Medicine, I came upon this irresistible conclusion:

Priceless!

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Quality or value? A measure for the 21st century

Fascinating, how in the same week two giants of evidence-based medicine have given such divergent views on the future of quality improvement. Here (free subscription required), Donald Berwick, the CMS administrator and founder and former head of the Institute for Healthcare Improvement, emphasizes the need for quality as the strategy for success in our healthcare system. But here, one of the fathers of EBM, Muir Gray, states that quality is so 20th century, and we need instead to shine the light on value. So, who is right?

Well, let's define the terms. The Merriam-Webster dictionary defines quality as "the degree of excellence." The same source tells us that value is "a fair return or equivalent in goods, services or money for something exchanged." To me "value" is a holistic measure of cost for quality, painting a fuller picture of the investment vis-a-vis the returns on this investment. What do I mean by that?

Simply put, the idea behind value is to establish what is a reasonable amount to pay for a unit of quality. Let's take my used 1999 VW Passat as an example. If my mechanic tells me that it needs to have some hoses replaced, and it will cost me under $100, and the car will run perfectly, I will consider that to be a good value. However, if my transmission has fallen out in the middle of Brookline Ave. in Boston (really happened to me once, many years ago and with a different car), and it will cost me $5,000 to fix, I may say that the value proposition is just not there, particularly given that the car itself is worth much less than $5,000. Given that my budget is not unlimited, I have to make trade-off decisions about where to put my money, so I may instead spend the money on another used Passat that has good prospects.    

But in medicine, we routinely avoid thinking about value. There seems to be an overall impression that if it out there on the market, and especially if it is new, it is good and I am worth all of it. This impression is further enabled by the fact that CMS has no statutory power to make decisions based on value of interventions -- they are legislatively mandated to turn a blind eye to the costs. Does this make sense? How toothless is our comparative effectiveness effort likely to be if it has to ignore half of the story?

Let us now look at my favorite sticky wicket, ventilator-associated pneumonia, or VAP. Now, the IHI bundle aimed at eliminating VAP consists of 5 points of intervention: 1). semi-recumbent positioning, 2). daily screen for readiness to get off mechanical ventilation, 3). daily sedation vacation, 4). prophylaxis against GI bleeding, and 5). prevention of clots. As I have mentioned before elsewhere, adherence of 95% to all these measures is deemed compliance and may be ultimately used as a quality measure by payers to determine levels of reimbursement. And while each of these interventions is basically "motherhood and apple pie", applying them blindly and in toto to 95% of intubated patients may be a strategy for disaster. But what is even clearer is that, in order to implement this and all of the other quality improvement strategies, systems need to be put in place that will safeguard against failing to implement these quality measures. The time and resource expenditures needed to institute and maintain these systems, which have not been described in great enough detail as far as I am concerned, have never been quantified. So, what we are left with is a bunch of interventions that, while looking OK individually in clinical trials (until you really start looking at them critically), are likely providing small, if any, gains in quality at the margins, whose investment-return equation has not even been disclosed, let alone balanced. And because budgets are necessarily limited, as are clinicians' time and cognitive capacities, we need to select a sensible menu of interventions from this practically unlimited feast.

This is the quality conundrum, a clear case of chasing our tails to achieve perfection at the expense of good enough. And while no one in their right mind will argue with the language of improved quality in healthcare, I do think that Muir Gray and his camp are on to something that has been a long time coming. At this time of shrinking budgets, competing priorities and tightening resources, does it not make sense to look at value as a package deal, rather than merely at quality in isolation from its context? Instead of being bombarded by ever-increasing volume of quality measures coming from many directions, would it not be more sensible to prioritize these interventions based on the value that they bring rather than merely on their projected outcomes benefits, so frequently estimated based on data that have very little applicability to the real world? Let's start asking the question: how much quality and at what price? Without paying attention to this critical balance, we will not only bankrupt the system, but also worsen outcomes paradoxically, as we continue to overwhelm clinicians with infinite minutia that may or may not be generating helpful outcomes.

So, in my book, Muir Gray: score; Berwick: keep trying.            

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Top 5 this week

#5: Redefining compassion: "A spiritual technology"
#4: CMS never events: Evidence of smoke in mirrors?
#3: The rose-colored glasses of early trial terminatio...
#2: Guidelines: What really constitutes level I eviden...

Drum roll for #1 post of the week: New treatments: What benefits at what costs

Thanks for stopping by and reading!

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Guidelines: What really constitutes level I evidence?

There has been some interesting buzz in the blogosphere about where evidence-based guideline recommendations come from, and I wanted to add a little fuel to that fire today.

As you know, I think a lot about the nature of evidence, about the "science" in clinical science, and about pneumonia, specifically ventilator-associated pneumonia or VAP. Last week I wrote here and here about a specific recommended intervention to prevent VAP consisting of semi-recumbent, as opposed to supine, positioning. This recommendation, one of 21 maneuvers aimed at modifiable risk factors for VAP, had level I evidence behind it. Given my recent deconstruction of this level I evidence, consisting of a single unblinded RCT in a single academic urban center in Spain, and given that we already know that level I data represent a very small proportion of all the evidence behind guideline recommendations, I got curious about this level I stuff. How is level I really defined? Is there a lot of room for subjective judgment? So, I went to the source.

In its HAP/VAP guideline, the ATS and IDSA committee define the levels of evidence in the following way:

Level I (high) Level II (moderate)  Level III (low)

Evidence comes from well conducted, randomized controlled trials Evidence comes from well designed, controlled trials without randomization (including cohort, patient series, and case-control studies). Level II studies also include any large case series in which systematic analysis of disease patterns and/or microbial etiology was conducted, as well as reports of new therapies that were not collected in a randomized fashion Evidence comes from case studies and expert opinion. In some instances therapy recommendations come from antibiotic susceptibility data without clinical observations

So, well conducted, randomized controlled trials. But what does "well conducted" mean? Seems to me that one person's well conducted may be another person's garbage. Well, I went to the text of the document for clarification:

The grading system for our evidence-based recommendations was previously used for the updated ATS Community-acquired Pneumonia (CAP) statement, and the definitions of high-level (Level I), moderate-level (Level II), and low-level (Level III) evidence are summarized in Table 1 (8). 

OK, then. We have to go to reference #8, or the CAP guideline to get to the bottom of the definition. And here is what that document states:

Therefore, in grading the evidence supporting our recommendations, we used the following scale, similar to the approach used in the recently updated Canadian CAP statement (46): Level I evidence comes from well-conducted randomized controlled trials; Level II evidence comes from well-designed, controlled trials without randomization (including cohort, patient series, and case control studies); Level III evidence comes from case studies and expertopinion. Level II studies included any large case series in which systematic analysis of disease patterns and/or microbial etiology was conducted, as well as reports of new therapies that were not collected in a randomized fashion. In some instances therapy recommendations come from antibiotic susceptibility data, without clinical observations, and these constitute Level III recommendations.

Again, we are faced with the nebulous "well-conducted" descriptor with no further defining guidance on how to discern this quality. I resigned myself to going to the next source citation, #46 above, the Canadian CAP statement:

We applied a hierarchical evaluation of the strength of evidence modified from the Canadian Task Force on the Periodic Health Examination [4]. Well-conducted randomized, controlled trials constitute strong or level I evidence; well-designed controlled trials without randomization (including cohort and case-control studies) constitute level II or fair evidence; and expert opinion, case studies, and before-and-after studies are level III (weak) evidence. Throughout these guidelines, ratings appear as roman numerals in parentheses after each recommendation.

Another "well-conducted" construct, another reference, another wild goose chase. The reference #4 above clarified the definition for me thus:

OK, so, now we have "at least one properly randomized controlled trial." So, having gotten to the origin of this broken telephone game, it looks like proper randomization trumps all other markers for a well-done trial. The price of such neglect is giving up generalizability, confirmation, appropriate analyses, and many other important properties that need to be evaluated before stamping the intervention with a seal of approval. 

And this is just one guideline for one syndrome. The bigger point that I wanted to illustrate is that, even though we now know that only 14% of all IDSA guideline recommendations have so-called level I evidence behind them, what is dubious is the value and validity of assigning this highest level of evidence to these recommendations, given the room for subjectivity and misclassification. So, what does all of this mean? Well, for me it means no foreseeable shortage of fodder for blogging. But for our healthcare policy and our public's health? Big doo-doo.

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