Trusting the medical literature

really nothing new...as always... just take it with a grain of salt
Dr RW has an interesting post where he responds to Dr Marcia Angells JAMA commentary where she questions the ability to practice evidence based medicine noting that "Physicians can no longer rely on the medical literature for valid and reliable information".

Though, as pointed out by Dr RW, there are prescient challenges and significant problems reagrding industry and non-industry supported research, Dr Angells assertion -reminiscent of the "pharma is all evil" canard- indeed seems far too simplistic.

Unfortunately, her opinion -though important and worth measured consideration- may be taken as fact and used by the ideological or the less scientifically literate to distract from a more balanced approach to considering a litany of real problems. Indeed, the research landscape is far from the useless state Dr Angell seems to claim.

As Dr RW notes:
"What then are practicing doctors to do? Angell’s statement above suggests that in the current environment the practice of evidence based medicine and science based medicine are impossible. Nonsense. EBM is premised on the fact that all research reports have weaknesses and are to be viewed with skepticism. SBM, recognizing that EBM lacks the tools to examine all claims, goes a step further by evaluating reports in light of prior research and scientific plausibility. In short, doctors have the tools to critically appraise the medical literature. It’s hard to believe Dr. Angell wants to abandon EBM altogether."
(My bold)

Hopefully that is not her intent. Dr Angell does seem to favor an "independent body" to serve as overseer and provider of clinical trails...an option fraught with many of the same problems beguiling the present research environment.

In the end, as these issues are -hopefully- objectively and pragmatically addressed, Dr RWs' call to using evidence and science based approaches and tools when evaluating data will continue to serve practitioners and their patients well.

Statistical Literacy Guide

DC's Improbable Science has an interesting link -the Statistical Literacy Guide- located in the UK commons library archive regarding the oft misunderstood and abused science of statistics.

This is a great read and introduces the reader to many of the nuances of statistical analysis and how these important tools can be inappropriately spun "a la politico" into down right meaningless and vacuous interpretations.

A very helpful piece for those of us trying to tease out real meaning from a sea of confusion regarding "new" (or old) research purported to "prove" or support grandiose claims that pop up from most every sector in the medical and -especially- the psuedo-medical world.

Medicines that contain no medicine and other follies

David Colquhoun wrote a very nice article regarding the blurring between "alternative medicine" and outright quackery and self delusion. This is an important statement in the struggle to redirect all too limited funds towards more appropriate areas of medical research.

It also brings to the fore a telling problem for Complementary and Alternative supporters. They just don't know when to call off or discontinue a modality when there is little or no supporting evidence of efficacy.

Some of the commentators I read on this humble blog seem to exude a mix of active denialism, ignorance or mistrust of scientific methodology and a curious rigid undergirding of belief based opinions not very amenable to objectivity.

Indeed, many in the CAM field defend their particular fixations (be it acupuncture, homeopathy, nutritional supplement...etc.) claiming "more studies are needed"ad infinitum, that you just can't properly test it -when you can if it's real, that it's "complicated" (appeal to complexity) or "you do it too" accusations (Tu Quoque).

They very commonly support demands and claims with an astounding quagmire of classical fallacious reasoning (dare I say mental masturbation) and resist reality and science based information - especially if it is unsupportive of their cause.

Dr Colquhoun nicely sums up some CAM modalities as follows (I'm sure to the shagrin of beleivers) thusly:

"Homeopathy: giving patients medicines that contain no medicine whatsoever.

Herbal medicine: giving patients an unknown dose of a medicine, of unknown effectiveness and unknown safety.

Acupuncture: a rather theatrical placebo, with no real therapeutic benefit in most if not all cases.

Chiropractic: an invention of a 19 th century salesmen, based on nonsensical principles, and shown to be no more effective than other manipulative therapies, but less safe.

Reflexology: plain old foot massage, overlaid with utter nonsense about non-existent connections between your feet and your thyroid gland.

Nutritional therapy: self-styled ‘nutritionists’ making unjustified claims about diet to sell unnecessary supplements."

At any rate, read the article when you can.

Detoxin' your wallet dry!

...on todays snake oils
Steven Novella at Nuerologica blog has -as usual- an excellent take down of some really juicy pseudoscience and related hubris that can only be described as classic scam artistry.

He notes "There is a cycle to the snake oil market - like the fashion industry. Words and claims come in and out of fashion, used for marketing impact rather than scientific accuracy. Some words, like “natural” and “energy” have staying power, while others last for a time and then may fade, but can come back into fashion like wide ties.... Recently “detox” is all the rage."

Dr Novella notes that the Sense about Science group is in the forefront of taking down the ridiculous and spurious claims purveyors of "detox" nostrums blantantly trumpet to a sadly creduluos populace.

As their Debunking Detox pamphlet puts it:

" The multi million pound detox industry sells products with little evidence to support their use. These products trade on claims about the body which are often wrong and can be dangerous."

Dr Novella concludes his post noting that "What the marketers of detox products have done is made the term “detox” meaningless - actually the term now is nothing but a red flag for snake oil."

On a related note, I was recently introduced to a "super juice" supplement product called Goji juice. Of course it's supposed to be nothing short of some miraculous nectar from the gods.

Not!

Under closer scrutiny, other than being made from dehydrated goji berrys from China, this product does not live up to the rather outlandish claims of many of its distributors (looks like fodder for a future investigative post!).

In fact, these wild statements are reminsent of the false hype and hyperbole from the Mangosteen crowd. It's the same old pimping up of some "exotic" special elixir....basically fruit juice in a golden wrapper. An interesting skeptical blog seeks to take this issue head on. I wish them well!

Prions: mysterious shape shifters

Everywhere and nowhere

It is the strangest thing to see a vibrant and healthy Colorado bred elk begin to shrivel and waste away before your eyes. It is even more frustrating to feel that old familiar tinge of complete helplessness when the realization comes to you that chronic wasting disease has taken (CWD) hold of another victim. No matter how aggressive and careful you are there is literally nothing that can be done once this mysterious disease takes hold.

Thankfully, the incidence of this prion based sickness is relatively rare and slow to ravage whole herds. This is good as the best we can do to control CWD is to monitor it by testing the tissues of captive adult animals that have died or researching “test and cull” methods for eradicating it from wild herds.

The mechanisms that make this disease so bizarre and counter intuitive starts with the causative agent – a prion- a small protein structure without any nucleic acid. They are described as “small proteinaceous infectious particles which resist inactivation by procedures that modify nucleic acids.”

This is indeed beyond strange. The idea that a protein structure by itself can cause disease defied a lot of what was known about infectious disease. The infected animals are usually neurological and the disease is now classified into a family of “spongiform encephalopathies” based on the post mortem lesions found in affected mammals¹- of which most seem to have some version of this thing (table 1). They are all characterized by varying degrees of loss of motor control, dementia, wasting (paralysis) and eventually death.

Table 1 some prion diseases:

• Scrapie: sheep
• TME (transmissible mink encephalopathy): mink
• CWD (chronic wasting disease): muledeer, elk
• BSE (bovine spongiform encephalopathy): cows
• CJD: Creutzfeld-Jacob Disease: human
• GSS: Gerstmann-Straussler-Scheinker syndrome: human
• FFI: Fatal familial Insomnia: human
• Kuru : human
• Alpers Syndrome: human

An interesting historical anecdote regarding early prion research is touched on by Dr Shaun Heaphy lecturer at the University of Leicester “Kuru is the condition which first brought prion diseases to prominence in the 1950s. Found in geographically isolated tribes in the Fore highlands of New Guinea. Established that ingesting brain tissue of dead relatives for religious reasons was likely to be the route of transmission. They ground up the brain into a pale grey soup, heated it and ate it. Clinically, the disease resembles CJD. Other tribes in the vicinity with same religious habit did not develop the disease. It is speculated that at some point in the past a tribe member developed CJD, and as brain tissue is highly infectious this allowed the disease to spread. Afflicted tribes were encouraged not to ingest brain tissue and the incidence of disease rapidly declined and is now almost unknown.” This rather macabre custom did illustrate how this strange infection behaved and how it might work through a population of people.

Even more intriguing, these prions seem to be related to a normal and abundant cellular protein (PrPc) located on the membrane on run of the mill neural cells. These prion like structures have a different structural shape than infectious prions and are perhaps functionally linked with normal neural transmission, though no one really knows for sure.

Prions and these PrPc proteins seem to have species specific structures but these configurations are fairly similar across the board. This species specificity dramatically slows down cross species infections and makes such jumps far less probable, but not impossible- especially if there is a susceptible individual on the other end.

The prion varies in its structural three dimensional forms from the normal PrPc protein and it’s this structural difference that seems to make them so insidiously pathological. To make matters worse, it seems there may be genetically susceptible individuals that are more prone to having their own PrPc proteins “shape shift” into the pathological infectious prion by coming into contact with a prion (by the way, not all shape shifted prions are lethal).

Interestingly, that it is possible to eventually “transform” an infectious prion from one species to another susceptible species is a prime example of witnessing evolution “unplugged” right before our eyes. The ability of these prions to evolve structurally and in time come up with the right configuration to cross species without any genetic elements is remarkable.

As ERV puts it “How does something with the same amino acid sequence evolve??”. With respect to prion research being done by Dr Bartz she adds “The idea I pitched to Dr. Bartz (the idea he was already planning on pitching to the scientific community hehe, I iz smrt) is that prions operate like HIV-1. But instead of exploring sequence space like my HIV, his prions explore structure space. One protein exploring all possible structural configurations. It has an optimal configuration for minks, but needs to explore and find a more optimal configuration for ferrets.” Amazing stuff!

What does a normal PrPc do? What makes its shapeshifted version so lethal? According to the Prion Institute “Studying how and why proteins misfold and the genetics, diagnoses and treatments of prion diseases will have positive implications for both animal and human health issues.”

Indeed, the possible breakthroughs for understanding the prion phenomenon may have staggering implications towards not just understanding the spongiform encephalopathies, but other degenerative neural diseases (i.e.; Alzheimer) as well as shed light on normal brain physiology. All this from a tiny inert blob of protein- reality is indeed far stranger than fiction.

------------------------------------------------------------

1) Visible end results at post-mortem are non-inflammatory lesions, vacuoles, amyloid protein deposits and astrogliosis.

Transforming Data

glimpes of evolution in the information age

Hans Rosling is founder and director of Gapminder, an interesting non-profit venture that promotes sustainable global development. He has breathed life into the world of numbers and managed to do what many thought impossible.

By developing a software program named Trendalyser he was able to “unveil the beauty of statistical time series by converting boring numbers into enjoyable, animated and interactive graphics.” The ultimate goal is to access all of the existing and accumulating informational data bases of the world – which are critically important yet often stored in archaic and difficult to reach places- and transform them into large interactive pools of information that display in incredibly useful formats.

The ability to get more out of the data is truly astounding and has global implications in developmental, economic, health, environmental and social sectors just to name a few. An example of what this technology offers can be seen in Roslings 2006 discussion “debunking the myths of the world.”

The potential for evaluating, examining, and understanding statistical information is staggering. In this way, better decisions and more effective solutions could be implemented. For example, trends in medicine could be tracked and correlations made that favor optimal health thereby improving our understanding of what does and doesn’t work.

These trends could be noticed quicker and targeted more precisely with much more nuance (i.e.; what subpopulations respond to what therapies). This could have a significant impact in science and evidenced based medicine in the near future and promises to make life easier for practitioners striving for the best medicine.

On a related note, there is a bourgeoning new generation of web based services in human medicine that promises to revolutionize how medicine is practiced. The ScienceRoll site has an excellent review of the possibilities.

Pet Foods: notes from the experts

Towards a greater understanding (part 2)

There are many variables that go into making informed decisions regarding what to feed a healthy dog or cat. Having a solid veterinary/ client relationship forms the foundation from where information can be sifted taking into account each pets unique circumstance in order to come up with a reasonable dietary plan.

Among the most important issues with respect to pet food is that we have to make dietary choices based on the best science and evidence available and avoid the allure of unsubstantiated claims. The big challenge here is that things aren't always clear cut. For example dog food companies, whole food advocates, and purported alternative nutritionists all -in one form or another- fall under the sway of faddism, premature nutrient recomendations, consumer driven demands, and market pressures.

The more informed we are the better. If our information is balanced, dispassionate and accurate then picking a path through this quagmire is easier. With that in mind, we can go back to the Veterinary Forum nutritional expert panel for more interesting discussion regarding pet food and the state of the industry.

On ingredients

This appears to be one of the most pressing issues when it comes to some of the common general misunderstandings. Part of the problem stems from a general lack of basic skills in science and general nutrition which can impede a more nuanced perpective of this complex issue.

At least some of the details regarding food ingredients, preservatives, additives, and other constituents need to be understood enough so that prudent choices can be made by veterinarians and pet owners. For example, a pet food company might cut corners too much, or someone may claim a certain chemical additive is just poison. Armed with the right tools, a person could effectively analyze the issue at hand and make a rational more balanced determination of the problem or claim and what to do about it.

One of the interesting points mentioned in the discussion was that people in general seem to lose sight of the fact in spite of the huge number of available foods products on the market, animal needs have not changed too dramatically. Delaney notes “the nutritional needs of dogs and cats really haven’t changed. Yet, so many new products are being introduced. Veterinarians need to start by understanding the nutritional needs of dogs and cats and the individual factors that affect those needs.”

A rough analogy is that a shirt and jeans are always the basic and essential part of a teen’s attire. You can dress it up, loosen the pants, change the colors, add jewelry, or add whatever puffery the teen demands; but in the end the jean and t-shirt never goes away.

A detailed discussion of all the common components of food such as micro and macronutrients is beyond the scope if this post. However, we will touch on one topic mentioned by the experts on the panel as an example of some of the issues involved with food sources and pet food ingredients.

There is a lot of misunderstanding regarding the meaning of macronutrients in pet food. These are the main components of a diet and comprise the bulk of for example proteins, fats, and carbohydrates. Freeman notes “There’s so much misinformation about ingredients on the list. For example, lamb listed as the first ingredients is sometimes perceived as better than a by-product, which has become a frightening term to some people. Yet, some labeling might list the first ingredients as beef heart, beef liver, or beef lung without the word by-product.” This belies a very basic problem with the attitude and general perception of what an acceptable macronutrient might be. Daristole adds that “Consumers may not understand that most of the macro-ingredients in commercial pet foods are indeed by-products of the human food industry, not because they are bad for anyone but because of food preferences.”

If one stands back and thinks for a moment, it becomes evident that these are big issues and could be barriers towards comprehending nutrition at the most basic levels. Roudebush very eloquently reminds the panel that “My grandfather and father grew up on farms, and when an animal was slaughtered, all of it was used. There were no by-products. We have gotten away from that practice. People who are entering veterinary medicine today have less of that background. Then, so much of it is cultural in the United States, where people are less accustomed to having contact with where our food comes from and how it is used.” This is not really a yearning call for days of old. It is an important observation that requires our attention as we try to navigate through the issues of pet food ingredients.

On the other hand, a promising and positive development has been the increasing consumer awareness of “greener” and more wholesome (organic) food ingredients as well as concern for how our food sources are handled and treated. This opens the doors to perhaps a more balanced approach to a host of agricultural practices and animal husbandry techniques.

Roudebush states that “The AAFCO manual defines organic as a formula feed or a specific ingredient within a formula feed that has been produced and handled in compliance with the requirements of the USDA natural organic program.”

The problem seems to be, that due in part to a “disconnected” consumer, terms and descriptions like “organic”, “nature”, and “human grade”(1) that supposedly denote some type of superiority either in production methods or nutritive value over “conventional” methods turn out to be more semantics than anything real.

In other words, we shouldn’t throw the baby out with the bath water when it comes to evaluating the pet (or human) food industry. Though a laudable ideal, the organic industry has its own “foot print” to contend with. The book “An Omnivores Dilemma” is a good introduction to the realm of food production and the challenges of feeding the masses well while balancing food gathering and distribution.

Raw, commercial, and homemade pet food

In and of itself, the concept of raw food diets is simply another way of delivering food to pets. The problem is when people claim that it is a superior method for feeding dogs and cats. Though still a fairly rare practice in the US (more common in Australia) it is on the rise and there are several companies that distribute different types of commercial raw food mixes.

According to Freeman “ there are no proven benefits linked to raw diets, yet there are multiple studies showing nutritional imbalances, both in commercial and homemade raw diets, and multiple studies showing contamination in the vast majority of raw diets. There is a risk for the people in the household but also for the pets themselves. So, in terms of raw-food diets the risks far outweigh any potential benefits.”

Freeman, Curchill, Laflamme and Tefend note that there are more reports of nutritional deficiencies and excesses with raw and homemade diets than with many commercial diets. Roudebush notes that no AAFCO maintenance feeding trials have been done on any homemade prepared diets and this is a problem when looking for evidence.

Laflamme mentioned that there have been two independent studies that “compared dogs fed commercial pet food with dogs fed homemade diets. The study (1999) I’m most familiar with involved 1,000 dogs in three different groups…There were significant differences in terms of health problems being greatly reduced by the feeding of commercial pet foods.”(2)

On the other hand, this is not to say that home made foods in general don’t have a place “on the table” and indeed can often be a critical part of the nutritional puzzle for some pets and for any owner willing to put in the effort needed to do it right.

However, they need to be complete and balanced and Churchill cautions that “I frequently see well meaning owners make substitutions to the recipe, until over time, ‘diet drift’ occurs, and the diet may no longer resemble the original formulation.”

McChesney and Churchill also add that salmonella risk is higher when dealing with the day in/ day out processing of homemade and especially raw diets and extra care needs to be given for maintaining routine hygienic standards. Cooking homemade food does not significantly diminish its dietary quality (problems with heat labile substances can be corrected) and reduces the risk of food borne disease.

Again, it is more advantageous to take note of the evidence, science, and -to a degree- the opinions of experts in the field. No, it’s not perfect and problems abound, but the ability to make the best decisions regarding what to feed our pets lies here and not on assumption, hearsay, what we’d like to believe.

(Part 3 touches very briefly on the recall and regulatory issues)

----------------------------------------------------------

1) Roudebush notes “According to AAFCO the term human grade cannot be used anymore. However the term continues to be used on websites, in brochures and on some labeling.”

2) Interestingly, there is an often repeated study alternative veterinary nutritionists fondly allude to that claims to support raw foods or the broad use of nutritional supplements. It is an old 1940’s report known as “Pottingers cats” that seemed to evidence multi-generational deficiencies in cats with cooked or “processed” foods. The more likely reality was that the affected cats suffered from other confounding issues such as a species specific sensitivity to taurine deficiency, a heat labile protein, that when added to a cooked diet corrects this problem.

Alternative medicine and fallacious arguments

Some impressions from reading recent CAM defender statements

Debating with alternative medicine apologists can sometimes be a tedious affair. Reading through posts on some of the threads going at the Science Based Medicine site (lots of activity there recently), it becomes evident that -knowingly or not- many of these folks tend to fall back on recurring themes.

It appears that some of these apologists do not appear to be interested in a frank and honest discussion of the issue at hand, but rather many insist on focusing on an almost reflexive and hermetic defense of their “pet” position. These CAM supporters appear to be oblivious to the sometimes enormous gaps between the solid weight of evidence against their topic “du jour” and the naked precariousness of their defense. This is a classic example of the cognitive dissonance often observed throughout CAM in general.

The following list just touches on some recent problems with the arguments of many CAM supporters I’ve noted that muffles effective communication and blunts open discussion (a more thorough examination of these arguments would likely uncover a host of even more fallacious reasoning):

1) A priori assumptions. This is taking the whole scientific process of observing phenomena to then eventually formulating a hypothesis about it and turning it on its head. Placing a conclusion first, then attempting to gather data that supports this view brushes away objectivity and completely disconnects the observer from reality. This is a recipe for creating a belief system and allows for abstractions far removed from what actually occurs. This approach reveals a deeper level of inflexible conviction that permeates their argument, crystallizes these beliefs, and makes them impervious to self doubt and critical analysis.

2) Mioptic views. Many CAM apologists tend to focus almost exclusively on one small area of the topic at hand. They discuss the fine details and deep intricacies of one drug or concept and completely miss a broader and more significant point. By obsessing on one tree many CAM supporters completely miss the entire forest of trees around them. One reason for this is because; the deeper they go on their merry journey the more they tend to lose connection with the broader base of scientific knowledge- this becomes a rabbit hole to no-where. This reasoning is a form of causal reductionism where so much attention is given to one variable that a whole host of other fatcors are not taken into account. This is where many obesity and cholesterol folks can sometimes get lost.

3) Vomiting data. This approach seems to be a favorite among many of the nutritional supplement apologists. You will suddenly be confronted with what appear to be reams of cold hard data supporting one pet theory, belief, or whatever. On closer scrutiny one finds that these studies or other data sources are cherry picked from a much larger body of evidence that –on its whole- is either inconclusive or actually argue against the CAM topic at hand. They are often obscure in detail or discuss a tangentially related topic and do not support the argument at hand. At times these sources are very old documents and disconnected from present day scientific activity (it is not uncommon to find no mention of them on PUBMED or any other scientific data bases).

4) Because of this/therefore that (confusing correlation and causation). Many CAM supporters like to inappropriately blend and confound their theories with others from an unrelated field. In quantum theory nonlocality and superposition are often correlated to the claimed health effects of many CAM modalities. Supporters seem to completely and blatantly ignore the real science in a spectacular misrepresentation of the facts literally making up a story that “fits’ their paradigm.

5) Repeating the same claim. This is an argument of repetition, where a CAM defender will seem to ignore a clear counterpoint, not address it, and continue to ramble on in a defense of their claim. A related version is when a supporter claims his/her counter claim was not addressed when in fact it was.

6) Lack of knowledge in the scientific method and critical thinking. This is a common thread throughout many CAM arguments. There seems to be a lack of understanding that science is a messy, complex, and often slow endeavor. Many want to bypass the rigors of this work and jump to a favored conclusion. On a similar vein, other CAM supporters will use the complex nature of scientific observation to “move the goalpost” and continually refine their defense beyond what is known. Many others take the tact of asking more and more questions eventually hitting on something an opponent may not be expert on (a demand to impossible perfection). They thereby claim a victory- hollow as it is.

7) Testimonials and emotional reasoning. This is a big one. It relates to not having a solid grasp on how probability and statistics "behaves". This reflects a lack of knowledge with respect to how real nature works. Appealing to these personal stories is the bread and butter of innumerable CAM modalities and is intimately related to aspects of delusion and, in many cases, outright deception.

8) Conspiracy theories. Claims of “the man”, big pharma, or some other ominous entity overseeing and buying off whole sectors of society are a favorite staple of many CAM defenders. These attitudes are reminiscent of mind sets that made Molder of the X- files so famous. This is a weak attempt to defend failed hypothesis without considering much simpler reasons for that failure. For example, that they actually do not work!

9) Ad hominem. When in doubt attempt to destroy the messenger. Though tired and repetitive, this is another reflexive reaction against those critically probing a CAM modality and seems to be as common as ever.

It’s the science stupid!

Alternative therapies and evidence based medicine don’t mix well

The science based medicine site has an interesting discussion that points out a major problem when researchers evaluate complementary and alternative medicine/veterinary medicine (CAM/CAVM) under the rubric of evidence based medicine (EBM).

The structure of EBM allows clinicians to objectively discern between varying qualities and levels of evidence for therapeutic efficacy regarding whatever modality is being considered. This system provides a solid statistical and epidemiological data base through the use of a variety of techniques. The goal is to create a reliable system of information from where clinicians can develop sound therapeutic decisions.

However, there has been a nagging problem that EBM seems to have difficulty resolving with respect to CAM/ CAVM research. It lies within the basic structure of EBM’s lack of ability to properly assess the science base of many therapies going into studies such as clinical trials.

In other words, EBM (like the Cochrane collaboration) has trouble if you take it beyond its primary mission. Dr Atwood notes “EBM…comprises sets of guidelines for assessing evidence...” These are systems designed to evaluate evidence based on therapeutic and clinical significance-and herein lays the problem.

EBM doesn’t consider that many of the types of testing it utilizes to create statistical information is not geared toward scientifically examining the therapy in question. For example, it can construct a long line of trials for homeopathy –imaginary as this modality is- and yet still allow the ebb and flow of statistical chance to offer up meaningless "weak positive" results. The problem here is that this gives wiggle room from where its practitioners, clinging to false hope, can call for “further studies.”

This is reminiscent of the garbage in/garbage out Achilles heal of many meta-analysis where, if one is not careful, low quality studies can be used to give a “result”- skewed as may be- that may lead to nowhere or worse. In this vein, many CAM/CAVM therapies that seek legitimacy through EBM standards of testing do not even qualify to be tested because they suffer from a far more basic flaw –they lack basic scientific plausibility.

EBM does not take this important detail into account and this often results in an endless loop of back ground noise -like static- of “equivocal” results. There is an accumulation of mostly meaningless interpretations of gibberish because the original input was flawed at a very fundamental level.

Dr Atwood notes “Some claims are so implausible that clinical trials tend to confuse, rather than clarify the issue. Human trials are messy. It is impossible to make them rigorous in ways that are comparable to laboratory experiments. Compared to laboratory investigations, clinical trials are necessarily less powered and more prone to numerous other sources of error: biases, whether conscious or not, causing or resulting from non-comparable experimental and control groups, cuing of subjects, post-hoc analyses, multiple testing artifacts, unrecognized confounding of data due to subjects’ own motivations, non-publication of results, inappropriate statistical analyses, conclusions that don’t follow from the data, inappropriate pooling of non-significant data from several, small studies to produce an aggregate that appears statistically significant, fraud, and more.”

The misinterpretations can be truly mind boggling. One way to avoid this maze of miscues is that, in order for a therapeutic modality to be properly evaluated by EBM, it must first be fundamentally sound from a scientific perspective. It needs to pass under the critical eye of plausibility and not waist the time and effort that EBM requires. In this way, many of the current endless streams of research by the NCCAM for example could finally be put to rest freeing monies for truly worthwhile research.

In discussing this garbage in/garbage out problem in EBM Dr Atwood optimistically adds “Most of those problems are not apparent in primary reports. Several have already been discussed or referenced elsewhere on this site: here, here, here and here, for example. Academics active in the EBM movement are aware of most of them and want to correct them—as a quick scan of the contents of almost any major medical journal will reveal.”

Evidence base medicine, in and of itself, is not the most efficient filter of dubious therapies without the all important underpinning of basic science. For the present then, it behooves readers of the research to study it with a sharp eye, learn from those schooled in its ways, and pay attention to the details- hard but worth the effort.

Science

…and how to know it when you see it

Every once in a while it is good to briefly review the general concept of what science is and how to separate it from other non-science based concepts.

Science involves a set of cognitive and behavioral methods designed to describe and interpret observed or inferred phenomenon- past or present- that are aimed at building a testable body of knowledge open to rejection or confirmation.¹ The crucial part of this is that science- the best system of gathering knowledge we have- grows over time as useful features are retained while non-useful items are eventually discarded based on the rejection or confirmation of the gathered testable knowledge.

Put another way, testable knowledge -a theory for example- needs to satisfy two fundamental requirements. First, it needs to explain the observed phenomenon better (more comprehensively) than other competing theories. Second, it has to be able to make testable predictions that are correct.

Non-science/pseudoscience

Michael Schermer put together ten questions² worth asking when trying to define the boundaries between science and non/pseudo-science that serve the inquiring mind well in the search for reason among, for example, the plethora of medical claims and therapies out there. They are as follows:

1. How reliable is the source of the claim?


2. Does this source often make similar claims?


3. Have the claims been verified by another source?


4. How does the claim fit with what we know about how the world works?


5. Has anyone gone out of the way to disprove the claim, or has only supportive evidence been sought?


6. Does the preponderance of evidence point to the claimant's conclusion or to a different one?


7. Is the claimant employing the accepted rules of reason and tools of research, or have these been abandoned in favor of others that lead to the desired conclusion?


8. Is the claimant providing an explanation for the observed phenomena or merely denying the existing explanation?


9. If the claimant proffers a new explanation, does it account for as many phenomena as the old explanation did?


10. Do the claimant's personal beliefs and biases drive the conclusions, or vice versa?

Here is another short list of considerations to have handy that help identify non-science based claims that was put together by Langmuir.^3,4 It's another set of tools that helps cut through much of the confusion when perusing the literature:

1) Claimed effect being studied is often at the limits of detectability.

Subjective visual observations replace objective instrumental measurements.

The maximum observed effect is produced by an agent of barely detectable intensity.

2) Investigators readily discard prevailing ideas and theories and disregard criticism of their new ideas and theories.

Investigators concoct new ad hoc theories to account for the phenomenon.

3) Investigators do not attempt critical experiments that could refute their new theory by determining whether or not the effect is real.

Experiments done by others that refute the new theory are disregarded.

Ref:
1) Shermer M. The triumph of the scientific method: The most precious thing we have. Skeptic 1(1):34-49. 1992

2) Shermer M , Scientific American, 285:5, November, 285:6, December2001

3) Dr. Irving Langmuir, 1932 Nobel Laureate, as condensed by DL Rousseau in: "Case Studies in Pathological Science: How the Loss of Objectivity Led to False Conclusions in Studies of Polywater, Infinite Dilution and Cold Fusion," American Scientist 80:54-63 (1992))

4) Ramey, DW (1998). Pathological Science. World Eq Vet Rev 3(2):25-27.

Orthomolecular veterinary medicine

…a trip to the twilight zone (ll)

There is no question that nutritional intake is a foundational pillar of any animals’ health and well being. Along with reproduction, adequate food intake is likely key to the supreme goal of survival- at least long enough to “get the job done’’. Animals and humans are living longer healthier lives today in part due to improvements in nutrient intake and significant research is under way to explore any potential advantages different foods and food profiles (i.e.; Mediterranean diet) might have.

Animal Veterinary Nutritionists and Certified Nutritionists among other qualified professionals continue to delve into the intricacies of nutrient actions. With such disciplines as biochemistry, genomics, physiology, and medicine the effort goes on towards expanding this nutritional knowledge.

There are an increasing number of novel avenues of study that are shedding new light on the meaning of “optimum” nutrition and whatever this really means. The evolutionary dietary histories of many species offer insight into how flexible or not their nutrient profiles might be and may add to our understanding of ideal nutritional parameters. For example, in humans, the evolutionary tale seems to suggest that we posses an incredibly wide and flexible nutrient range where nutritional needs can be met in many different ways depending on the conditions- “optimum” nutrition may not even really exist as we might imagine!

Enough is known to realize the importance of maintaining nutrient intake during times of stress and disease. It’s a no brainer that it significantly impacts therapeutic outcomes. That nutritional consideration in medicine has been somewhat under the radar and given less importance than it deserves is a problem that is being remedied with increasing urgency. The coming deluge of retiring baby boomers, for example, demands increasing attention to a host of health and social issues including nutritional considerations.

However, as mentioned in other posts, there is still much to be gleaned, a huge tangle of complex data needs sifting, and in some cases more studies need to be completed before some promising ideas can be implemented.

So, it was with some interest that a glossy promotional mailing caught my eye highlighting an upcoming veterinary nutritional seminar. Unfortunately the title “Nutritional Integrative Therapeutics” immediately sent up red flags as “integrative” and “nutritional therapeutics” are often utilized to dress up alternative or less mainstream practices. A further perusal of this promotion revealed a familiar pattern- learned during a brief naïve experience of my own- of classic descriptors for a pseudo-scientific nutritional supplement support program.

The lecturer states “From cancer, heart disease and allergies, to arthritis, anxiety, and nervous conditions, some level of nutritional deficiencies can be traced to every disease condition in the world today” This is only a slightly more nuanced yet typical non sequitor of fallacious causality that is often prostetlyzed- usually to a ready audience.

The reasoning behind believing, as implied here, that disease is a product of nutritional deficiencies is based on a long history of claims- albeit unsubstantiated- and has allowed some in the supplement industry the opportunity to capitalize on an eager and credulous consumer.

In this particular promotional program, there are two topics of interest worth mentioning. They illustrate some of the dissonant thinking commonly encountered in the world of pseudo-scientific discussion. First, the seminar starts with a lecture titled “Whole food nutritional vitamin complexes…and how they differ from synthetic vitamins”- they really don’t as discussed in a previous post.

Second, a large portion of the seminar is dedicated to something I had not seen before- at least under this title “Orthomolecular Nutritional Medicine” with the following descriptor: “Using nutritional components to augment your current medical protocols and gain greater patient response in disease…improving immune function….”

This particular section, it seems, is especially laden with significant pseudo-science. “Orthomolecular” and “augmentation” seem to be interchangeable terms often used to describe the concept of treating disease with nutrient supplements as therapeutic compounds- as in mega-vitamin therapy- a fairly common and unproven alternative nutritional modality.

A simple data search on “orthomolecular medicine” opened the doors to a strange world of peculiar medical claims and a strange cast of characters including the great novel prize winner Linus Pauling and his infamous and bizarre vitamin C obsession. Though his well known antics deserve consideration, its the other weirdness that is of interest today.

The Orthomolecular Medicine Online site notes that “Orthomolecular medicine describes the practice of preventing and treating disease by providing the body with optimal amounts of substances which are natural to the body...The key idea in orthomolecular medicine is that genetic factors affect not only the physical characteristics of individuals, but also the biochemical milieu. ”

This introduction sounds reasonable at first glance- until you read further. Another page on this site describes the principles that define orthomolecular medicine (OM)¹. It is a rambling essay that bounces between holistic and conventional descriptions of OM in an attempt to have your cake and eat it too.

For example the author notes “On the one hand we are confused with Holistic Medicine; on the other we are seen only as the avant garde of orthodox medicine. In hopes of defining our true identity let me update the concept of OM as a new medical specialty.” Later he continues “First of all, the orthomolecular data base rests strongly on the following areas of scientific knowledge: 1.nutrition 2. biochemistry 3.cell biology…10. toxicology…12. parasitology…19. climatology 20. medical politics.” He then goes on to say “The following therapeutic modalities fit the definition of orthomolecular: 1. vitamins 2. minerals…6.enzymes… 9. cell therapy, 10. chelation therapy…17air ion therapy…20. acupuncture…23. biofeedback. 24. hypnotherapy…” This seems to be an attempt to cover all the bases, make everyone happy, and essentially not say a thing!

Essentially it seems that with OM you can treat disease with nutrients, enzymes, hormones, among other things. Finding the right amount to give of these substances for “optimal” dosage is difficult because laboratory tests don’t really reflect the patients’ nutrient status and you really can not rely on statistical models because of “biochemical individuality”; therefore “therapeutic trial and dose titration is often the most practical test.” Folded within these claims is an outright rejection of evidence based medicine and research. Another page attempts to minimize scientific methodology and the lack of evidence for OM stating that “Although double-blind studies are an important part of the scientific endeavor to find the truth, so to, are observations...Then, too, in a broad sense science incorporates philosophy. Some point out that science, too, must recognize that experiments once observed by a observer, become changed by the act of observation. The character of scientific procedures places restriction on the relevance of results.” This is classic complementary and alternative medicine (CAM) cognitive dissonance at its best.

This is also evident in some of the interesting discussions of other diagnostic tools such as chromatography, electrophoresis, and mass spectrometry where the science of “metabolomics” might produce an effective means of obtaining a rich and unique “cellular metabolic fingerprint.”

This forms part of the nascent science of nutrigenomics where “New types of functional foods with proven health claims could be developed, and perhaps personalized diets created…” So far, this is conjecture and may or may not provide some helpful information in the future. The problem is that OM and OVM seem to have created a world of clinical maladies and treatments with minimal solid and durable evidence.

The story of nutritional supplement companies making assumptions and hijacking ideas (some of which may prove to be sound at some level) has a long and convoluted history and parallels, to a degree the “snake oil” trade of other centuries.

Refocusing on the veterinary side, a search for veterinary related sites or information regarding OVM presented several complementary and alternative veterinary medicine (CAVM) sites that mention OVM in conjunction with a variety of other modalities (i.e.; acupuncture, homeopathy, herbal therapy) and mirror the above discussion on OM.

According to one web site, the advent of orthomolecular veterinary medicine was initiated by a Dr Belfield in the 1960s’ via the administration of injectable sodium ascorbate (vitamin C) to a dog infected with Canine Distemper. His bio page “There is a tendency by many, in and out of the healing sciences, to trivialize vitamins and minerals beyond the treatment and prevention of deficiency diseases. Dr. Belfield has made a giant step beyond this archaic perception by administering nutrients in gram amounts that will treat, prevent, and control conditions other than deficiency diseases.” The page goes on to critique “conventional” nutritional concepts and prop up OVM. This is basically the same old OM discussion regarding nutritional therapeutics. That is, basing theory and treatment more on the promise of an idea rather than -to name a few- reliable amassed data, controlled studies, and a well honed scientific consensus.

The Veterinary Institute of Integrative Medicine and the American Holistic veterinary Medical Association both have similar descriptions of OVM on their sites. The VIIM site mentions environmental and individual deficiencies adding “Orthomolecular medicine becomes necessary because of variability in food quality due to soil depletion or contamination and because individual patients have unique nutritional needs depending on heredity, health status, and lifestyle.”

Additionally, this site promulgates a publication titled “Veterinarians Desk Reference of Natural Medicines” that combines different conditions and diseases with recommended nutrient products. Similar booklets and publications exist for a variety of supplement companies and their specific products creating an impossible quagmire of different treatments and protocols and “a fast and loose with the facts” approach- partly due to lax regulations and intense industry competition.

Coming back to the little veterinary seminar that started this whole adventure, it seems one successful method for making CAVM modalities more mainstream is to provide educational seminars analogous to regular continuing education courses given throughout the country and layer them with a veneer of legitimacy. This particular seminar for example, allows for certain credit hours that may count towards veterinary practitioners’ continuing education hours per year- an obligation in the states.

With very little probing, the wording and make up of this veterinary informational seminar- while superficially innocuous- quickly takes on familiar CAVM overtones and directly associates it with some very serious pseudo- science. Whatever sound information this seminar may have is drowned and diluted by the insidious nature of integrating incompatible non-science with science. You inevitbly end up with a pile of garbage.

------------------------------------------------------------

1) Among the mentioned areas of established sciences that OM claims to depend on, in part for its “data base” are the veterinary sciences- so we can probably safely describe this area as orthomolecular veterinary medicine or OVM