What Is Missing From The Divisiveness Debate?

Migratory routes of Homo heidelbergensis from East African origins (numbers are approximate years in past) - see attribution for reference.  Homo heidelbergensis is thought to be the common ancestor for Neanderthals, Denisovans, and modern humans - Homo sapiens.

The recent high profile incidents involving the shooting deaths of young black men and police officers and the associated news coverage and involvement by high profile celebrities and politicians has sparked a social activism, debate, and dialogue.  Like any complex issue, there are people who have opinions that mirror their political party lines, people who have their own opinions and they are not interested in changing them and people who are more open to a dialogue.  Practically all of the dialogue seems focused on high risk incidents that happen in a matter of seconds that involve deadly force.  I have seen some neuroscientific ponderings about how unconscious or implicit biases can affect those split second decisions.  I thought that was possible until I went to the web site and took the tests involving implicit bias.  There was not a single case where I could not predict the outcome ahead of time based on what I already know about myself.  To me it appeared that unconscious bias was not operating in the decision.  Since I am a white psychiatrist and not a police officer, I am not going to suggest specific solutions for police officers or the black community.  I do see a number of scientific dimensions that nobody or very few people are talking about so it is time to add my two cents:

1.  We are all from Africa -

Practically all of the debate centers on race.  There are statistical studies that show black drivers are stopped at higher rates than white drivers.  There are more white people killed by the police but as a proportion of the population black people are overrepresented.  The numbers are real and require serious analysis, but the larger picture is ignored.  That larger picture is that race is a social and cultural convention and not a scientific one.  On a scientific basis, everyone in the world - all human beings originated in East Africa about 200,000 years ago.  At some point, different races were described but at the time this genetic evidence was unknown.  The genetic evidence for racial and ethnic differences is still an area of active investigation.  Those studies illustrate the difference in skin color for example may come down to mutations in two genes (1, 2).  At the proteomic level, a recent study (3) looked at an analysis of interindividual variation in the total number of proteins that could be identified in cerebrospinal fluid (CSF) and urine and found considerable variation between individuals.  There was a 26% difference across 968 urinary proteins and a 18% difference for 512 CSF proteins.  Those numbers are very large compared with the difference between 1 or 2 skin proteins.

Although the total number of proteins identified in the human proteins is 10,500, estimate of the true size has varied from 10,000 to several billion (4) making the number of proteins responsible for skin color differences even less significant.  More skin specific information is available from the Human Protein Atlas.  Their analysis shows that there are 95 skin enriched genes and 412 genes with enhanced expression in the skin.  Only three of these genes MLANA, DCT, and TYR involve melanin synthesis or skin pigmentation.  Person to person variation on an arbitrary racial classification based on skin color is obscured by the expected genetic variation among members of the same race.

Further evidence is available to anyone by sending their DNA for analysis by the National Geographic Genographic Project.  You will receive a map of how your ancestors migrated from East Africa and information about marker that you share with other ethnic groups across the world.  The analysis will also include information about DNA that you share with ancient humans specifically Neanderthals and Denisovans.  The current project also estimates regional ancestry based on markers that appeared over time if migration from Africa occurred.  All of these science considerations should point to the fact that what we have generally considered to be racial boundaries may have political and cultural meaning to people - but there is no scientific meaning.  Every human being on the planet is descended from a small group of ancestors in East Africa.  Time to put the cultural and political stereotypes about race behind us.        

2.  Every person in the world has a unique conscious state -

One of the concepts that I am careful to mention whenever I am discussing aspects of psychiatric diagnosis is human consciousness.  From a neurobiological perspective the human brain has evolved to be a very efficient information processor.   Plasticity leads to experience dependent changes in the brain.  Experience can have a biasing effect of the general form that "my experience is everyone's experience" or "my experience is more valuable than anyone else's experience" or in the extreme case "my experience is the only one that counts."  Fortunately the human brain also has top-down controls like empathy, the ability to recognize that other unique conscious states exist, and the ability to correct its own erroneous biases.  Just the fact that every person on earth has a unique conscious state has significant ethical and moral implications for how one person interacts with another.  Those individual ethical imperatives are seriously watered down by political and legal limits that often target the lowest common denominator.    

3.  Anger has a predictable biasing effect -

Let me start off by saying that this paragraph is not meant to discount anyone's anger.  Anger is a universal human emotion, but the analysis of anger usually stops at the point of whether it is justified or not.  The analysis seldom looks at how anger biases subsequent decisions or how it might affect the initial encounter between the police and suspects.  Any student of social media can observe the very predictable polarizing arguments that occur following these incidents.  Partisans will frequently post arguments and counterarguments followed by statistics and counter statistics.  In many cases the arguments are rhetorical at at some level fallacious.  The dynamic driving these arguments is never mentioned and that dynamic is anger.  Anger has been studied by cognitive scientists and it functions to squarely focus blame on a specific person whether that is accurate or not.  This is as important for the police officer on the scene as it is for the secondary clashes between protesters, the public and the police.  When police officers confront a suspect and start swearing angrily at him/her to comply with their demands - that may be part of their training, it may be something that happens spontaneously, but in either case any real anger on the part of the officer implies that the subject has done something wrong and that the officer's decision-making capacity may be affected by his/her emotional state.  Emotions are critical in human decisions, but not all emotions result in a focus on another person as a source of wrongdoing.  

4.  Human reaction time is a limiting factor - 

The human nervous system takes time to process information.  There is surprisingly little public data available on how much time there is to make a decision to shoot an armed suspect.  The only study I could find (6) involved a simulation where an untrained armed suspect was either holding a handgun to his own head because he was allegedly suicidal or holding a handgun at his side when confronted by a police officer.  In the case where the suspect decides to fire a shot at the officer instead - it took an average of 380 msec.  Highly trained officers shot in 390 msec.  That translated to inexperienced suspects shooting first or tying the officers in 60% of the scenarios.  An interesting article in the literature also suggests that shooting errors in high threat situations persist even after weeks of practicing these scenarios (7).  For comparison, this web site allows for a determination of reaction time in a scenario that is completely free from distractions and noise - like anxiety and trying to determine if what the suspect is holding is really a firearm or not.  It is obvious that these decisions to fire by both officers and armed suspects are not like they are portrayed in television programs and films.  In real life there are no prolonged standoffs with officers and suspects pointing firearms at one another while they talk.    


5.  Human beings have a long history of solving difficult problems through violence and aggression -

One of the major lessons of human history is that lives matter only up to a point and if nobody agrees at that point - people will die.  In human history there are very few exceptions to that concept.  The best analysis of the situation that I have seen comes from anthropology (8) and the detailed study of modern and ancient warfare.  Several authors have written about the attractiveness of war to some of the participants - most prominent Chris Hodges (9).  The powerful combination of war and winning a conflict by force and being reinforced by the secondary aspects of camaraderie, teamwork, meaningfulness, and the political illusions of what an armed conflict can accomplish are all powerful incentives to avoid peace and conflict resolution.  The last time there was as serious peace movement in the USA it was largely a reaction to a prolonged and unnecessary war in Vietnam.  Since then there have been three unnecessary wars and no corresponding peace movements.

The war metaphor doesn't stop at the level of nations fighting nations.  At the next level it is always local governments and police departments fighting drug dealers, gangs, terrorists and various criminals.  I don't think that the reinforcers that occur at a global level stop just because the conflict is at a local level.  Americans in general want to see the bad guys stopped in any way possible.  With that attitude there are invariably serious mistakes.    


6.  Widespread availability of firearms ups the ante -

I have written about firearm related issues in many places on this blog.  My primary focus have been to suggest that violence, especially firearm related deaths including suicide, homicide, and mass shootings can probably be stopped by public health measures.  Very few people agree on those points and there are various political reasons why they do not.  Stopping firearm related violence does not necessarily require addressing firearms availability, but make no mistake about it - firearms access rather than mental illness is the number one cause of these deaths.  The problem with high risk scenarios involving either firearms or the threat of firearms with the police is even more obvious.  Statistics are available for the number of people killed by the police in a number of countries and the numbers are skewed in the expected manner toward the US.  It is clear that widespread availability of firearms is dangerous for both the police and the people who are being policed.  A lot of that comes down to being able to assess the threat and react in less than a half second.  That is the time a police officer has in a high threat scenario.

The six dimensions I briefly described are critical but unmentioned in the current debate.  The current debate is framed in terms of race, immutable interracial relationships, and a lack of scientific consideration at several levels.  At the cultural level, the notion of race having some specific meaning needs to be put to rest forever.  There is no scientific basis for classifying people based on skin color or other so-called racial characteristics.  Racial diversity is nothing compared with genetic diversity and that needs to be the new standard.  The second scientific consideration is based on the unique conscious state of humans.  This important concept should form the basis for everyone being treated with respect and consideration.  That is not to say that will preclude criminal conduct or violent acts against bystanders, but it should be a standard for everyone else.  The expression of anger especially sustained anger has a particular biasing effect that is never mentioned.  We hear that anger is appropriate or justified, and therefore it should be expected.  Appropriate, justified and expected anger still affects human decision making in a predictable way.  The angry - no matter who they are need to realize that they may not be seeing things clearly due to the predictable and biasing effects of that emotion.  The technical aspects of human reaction time and the fact that decision making in high threat situations does not improve - even with training is a sobering fact that all police officers need to deal with.  Given the quoted statistics, in high threat situations when a subject is armed - the outcome of that confrontation will essentially be a coin toss.  The only logical approach to the situation is to design a new situation where it does not come down to reaction time and every officer knowing they have a 50:50 chance of being able to shoot first.  There is an innate human tendency for conflict resolution by aggression and choosing sides on how that plays out is not the best way to resolve the problem.  All that I have seen in social media and the press highlights a string of arguments designed to support one side or the other.

Considering the science behind this problem will lead to permanent, long term solutions.          



George Dawson, MD, DFAPA


References:

1: Murase D, Hachiya A, Fullenkamp R, Beck A, Moriwaki S, Hase T, Takema Y, Manga P. Variation in Hsp70-1A Expression Contributes to Skin Color Diversity. J Invest Dermatol. 2016 Apr 16. pii: S0022-202X(16)31047-8. doi: 10.1016/j.jid.2016.03.038. [Epub ahead of print] PubMed PMID: 27094592.

2: Yoshida-Amano Y, Hachiya A, Ohuchi A, Kobinger GP, Kitahara T, Takema Y,Fukuda M. Essential role of RAB27A in determining constitutive human skin color. PLoS One. 2012;7(7):e41160. doi: 10.1371/journal.pone.0041160. Epub 2012 Jul 23. PubMed PMID: 22844437; PubMed Central PMCID: PMC3402535.

3: Guo Z, Zhang Y, Zou L, et al. A Proteomic Analysis of Individual and Gender Variations in Normal Human Urine and Cerebrospinal Fluid Using iTRAQ Quantification. Pendyala G, ed. PLoS ONE. 2015;10(7):e0133270. doi:10.1371/journal.pone.0133270.

4:  Elena A. Ponomarenko, Ekaterina V. Poverennaya, Ekaterina V. Ilgisonis, et al., “The Size of the Human Proteome: The Width and Depth,” International Journal of Analytical Chemistry, vol. 2016, Article ID 7436849, 6 pages, 2016. doi:10.1155/2016/7436849.

5:  Skin specific proteome.  The Human Protein Atlas.  Accessed on 7/16/2016.

6:  Blair JP, Pollock J, Montague D, Nichols T, Curnutt J, Burns D.  Reasonableness and reaction time.  Police Quarterly Dec 2011; 14: 323-343 (especially pages 15-20).

7:  Nieuwenhuys A, Savelsbergh GJ, Oudejans RR. Persistence of threat-induced errors in police officers' shooting decisions. Appl Ergon. 2015 May;48:263-72. doi: 10.1016/j.apergo.2014.12.006. Epub 2015 Jan 16. PubMed PMID: 25683553.

8:  Lawrence H. Keeley. War Before Civilization. Oxford University Press, 1997.

9:  Chris Hodges.  War Is A Force That Gives Us Meaning. Public Affairs, New York, New York, 2002.

Attributions:

Attribution:  Graphic at the top is by Altaileopard SVG by Magasjukur2 [CC BY-SA 2.5 (http://creativecommons.org/licenses/by-sa/2.5)], via Wikimedia Commons at: https://upload.wikimedia.org/wikipedia/commons/4/41/Spreading_homo_sapiens.svg

Gout - Another Comparison Illness

The word gout in the above opening sentence from the chapter in UpToDate (1) can be replaced with any one of the major psychiatric disorders.  Gout is an extremely painful arthritis affecting one or more joints during an acute attack.  The arthritis is caused by the deposition of monosodium urate (MSU) crystals in the joint.  In a recent survey gout sufferers describe the pain as the worst pain they have ever experienced in their life - worse than childbirth or a heart attack (2).  Unlike psychiatric disorders gout has a gold standard diagnosis of the direct observation of uric acid crystals as being birefringent in a polarizing microscope, but only about 10% of gout sufferers ever has this test done.  The epidemiology of gout in the USA suggests that the prevalence is increasing to about 3.9% of the population or about 8.3 million people.  It is more common in men (5.9%) than women (2.0%).  There is an expected increase associated with obesity, hypertension, metabolic syndrome and aging.  Certain medication like diuretics can also cause increases in uric acid levels. but most people with hyperuricemia do not have gout.  The misdiagnosis of gout is common with gout sufferers being diagnosed with sprains and other forms of arthritis.  The inflammatory response is so striking that a misdiagnosis of cellulitis can also occur.  Searching Medline, I could not find a single study on the rate of misdiagnosis of gout.  Common biases that affect misdiagnoses include the over reliance on uric acid levels and demographic factors like age and sex of the patient.  Some earlier guidelines suggested an empirical trial of medication to lower uric acid levels and if that was ineffective to consider other diagnoses.

The pathophysiology of gout is interesting because it has been historically viewed as a disorder of uric acid intake, overproduction or undersecretion.  Intake is from dietary sources and there are numerous  resources that examine the purine content of foods.  Alcohol intake also directly increases uric acid production through increased metabolic demands by the liver.  The dietary approach is not uniformly accepted by physicians as a useful approach to treatment.  Many consider it to be a minor contributor to serum uric acid levels.  There is some data to support the use of low fat dairy products as a protein source and Vitamin C as a way to decrease the frequency of acute attacks.  Common claims include the use of grape and tart cherry juice as ways to decrease uric acid levels.  Internet information suggest that grape juice transiently lowers level but tart cherry juice provide more permanent decreases.  The only medical reference that I could find on grape juice was dated (4), but the references on tart cherries and cherry juice seemed excellent (5,6).  One group of authors (5) suggested that after 4 months of ingesting cherry juice there was a 50% reduction in gout attacks and patients were able to stop regular intake of non-steroidal anti-inflammatory after 60 days.  Cherry juice intake also protected patients with elevated uric acid levels from attacks.  In another study they used pomegranate juice as a comparator and it had no effect on the frequency of gout attacks.  Apart from the cherry juice evidence there is also some controversy about whether high purine content vegetables are as likely to precipitate a gout attack as meat products with high purine content.

Xanthine metabolism is intimately liked to glycolysis, so that increased metabolic demands can lead to increased uric acid production.  Common examples of how these pathways are activated in gout include excessive alcohol intake with increased metabolic demand and excessive intake of sugar sweetened beverages.

Uric acid secretion and reabsorption is captured in this graphic that attempts to address both the transport mechanisms as the uric acid transportasome and the expectedly complex genetics.  Thinking about the proteins coded for in uric acid metabolism and the transportasome,  this is clearly another complex polygenic disorder.  The diagram depicts uric acid transport in the proximal renal tubule.  The complexity of the involved mechanisms has increased significantly in the past decade.  Sodium dependent monocarboxylate transporters SLC5A8, SLC5A12 and SLC13A3 allow uric acid to accumulate in the cell.  A number of transporters allow for uric acid secretion.  In the case of OAT1 and OAT3 the direction of uric acid transportation is not clear.  PDZK1 is involved in assembling the transporter complex.  Genetic variants at all of these levels are associated with gout.

From: Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10. (reference 7)

Merriman's review of the genetics of gout emphasizes how the complexity of the disorder is not appreciated.  Preliminary genetic studies for example indicate that there are hundreds of potential genotypes affecting the involved proteins as well as epigenetic factors to explain the environment influence on the genomics, but they would only account for about 10% of gout patient with elevated levels of uric acid.

The lack of a complete explanation for gout based historical precedence has led some innovative researchers to look for an explanation in the inflammatory arm of the illness rather than the deposition of MSU crystals.  Gout is a highly inflammatory condition in the acute phase and there has been scant attention paid to potential phenotypes.  Some patients will get very localized pain and swelling in a clearly demarcated joint space.  Other will get marked swelling, edema, erythema, in multiple joints of the ankle and foot.  In some cases there is inflammation and swelling of the surrounding tendons and connective tissue.  In other extreme cases there is blistering of the skin surface over the affected joint.  Gout gives meaning the to the term "hot joint".  The most straightforward explanation for the inflammatory response was initial complement protein activation at the surface of the MSU crystals.  That leads to phagocytosis of the crystals by macrophages and generation of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, and TNFα).  Neutrophils are recruited and superoxide and IL-8 are generated.  Macrophages eventually take up MSU crystals and apoptotic neutrophils and generate transforming growth factor (TGFβ).  MSU crystals are coated with apolipoprotein B (ApoB)  and ApoE blocks further activation of complement proteins.  The inflammation resolves and the joint is reset back to baseline.

There are alternate mechanisms proposed  that involved the NLRP3 inflammasome.  That leads to caspase-1 activation and secretion of IL-1β, IL-18 and other proinflammatory cytokines (IL-6, IL-8 and TNF).  That leads to neutrophil infiltration of the joint and periarticular tissues.   The  authors in reference 8, emphasize the importance of the IL-33/1RL1 axis and polymorphisms in genes that code for IL-33, IL-1RL1, IL-23R and STAT4 as candidate genes for the inflammatory response in gout.  They determined that the IL-23R rs10889677 AC or CC genotypes were much more likely to develop gout than the AA genotype.  Other research groups have determined associations with inflammatory candidate genes and rheumatoid arthritis, asthma, Alzheimer's disease and Crohn's disease.  

What  are the implications for psychiatry and why is a psychiatrist interested in the details of the inflammatory response?  The first reason is the diagnostic process in medicine and the myth the gold standard or some kind of biological test.  In the case of gout a biological test exists, but hardly anyone uses it.  There are good reasons for that.  It takes a considerable amount of skill to successfully aspirate an inflamed joint.  If there is significant inflammation around the joint that means pushing a needle through all of that inflammation to get to the joint.  Physicians vary significantly in their ability to insert needles into joints and based on that skill level - it may be good idea to avoid a test even if it is the gold standard.  There is also a likelihood that even when the gold standard test is done, the test misinterpretation rates are high - maybe close to 50% according to a poster session mentioned in one of the references.  The second reason is that there is a diagnostic feature here that is almost pathognomonic of the illness, even without that feature.  A person with acute onset of joint pain, in the absence of other conditions is highly likely to have gout.  The Agency for Healthcare Research and Quality and the American College of Rheumatology/European League Against Rheumatism collaborative initiative have taken two different approaches in providing assessments of gout diagnosis algorithms with and without a gold standard test and assessed their accuracy based on available data.  Third, inflammation has current and historical importance in psychiatry both as a treatment and potential etiology for psychiatric illness and there may come a time when psychiatrists need to know more about it on a routine basis for refining diagnosis and treatment methods.  Finally, complex polygenic illnesses are difficult to diagnose and treat.  That is becoming more apparent as molecular biology shows us that the first efforts at determining the pathophysiology of these disorders may have been grossly correct - but that the diagnosis requires a lot of refinement in order to capture the full range of pathophysiology that may account for the illness.     



George Dawson, MD, DFAPA




1:  Becker MA.  Clinical manifestations of gout.  In: UpToDate,  Schumacher HR, Romain PL (Eds), UpToDate, Waltham, MA.  (accessed on July 10, 2016).

2:  Liddle J, Roddy E, Mallen CD, Hider SL, Prinjha S, Ziebland S, Richardson JC. Mapping patients' experiences from initial symptoms to gout diagnosis: a qualitative exploration. BMJ Open. 2015 Sep 14;5(9):e008323. doi: 10.1136/bmjopen-2015-008323. PubMed PMID: 26369796; PubMed Central PMCID: PMC4577947.

3: Newberry SJ, FitzGerald J, Maglione MA, O'Hanlon CE, Han D, Booth M, Motala A,Tariq A, Dudley W, Shanman R, Shekelle PG. Diagnosis of Gout [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK350137/ PubMed PMID: 26985540.

4:  LOEPER J, TISSEYRE JC. [Contribution to the uricosuric property of grape juice]. Prog Med (Paris). 1960 Nov 24;88:384 passim. French. PubMed PMID: 13763105.

5:  Schlesinger N, Schlesinger M. Previously reported prior studies of cherry juice concentrate for gout flare prophylaxis: comment on the article by Zhang et al. Arthritis Rheum. 2013 Apr;65(4):1135-6. doi: 10.1002/art.37864. PubMed PMID: 23334899.

6:  Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum. 2012 Dec;64(12):4004-11. doi: 10.1002/art.34677. PubMed PMID: 23023818; PubMed Central PMCID: PMC3510330.

7:  Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10;17:98. doi: 10.1186/s13075-015-0609-2. Review. PubMed PMID: 25889045; PubMed Central PMCID: PMC4392805.

8: Liu S, Zhou Z, Wang C, Guo M, Chu N, Li C. Associations between interleukin and interleukin receptor gene polymorphisms and risk of gout. Sci Rep. 2015 Sep 24;5:13887. doi: 10.1038/srep13887. PubMed PMID: 26399911.

9: Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, Brown M,Choi H, Edwards NL, Janssens HJ, Lioté F, Naden RP, Nuki G, Ogdie A, Perez-Ruiz F, Saag K, Singh JA, Sundy JS, Tausche AK, Vaquez-Mellado J, Yarows SA, Taylor WJ. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2015 Oct;74(10):1789-98. doi: 10.1136/annrheumdis-2015-208237. Erratum in: Ann Rheum Dis. 2016 Feb;75(2):473. PubMed PMID: 26359487; PubMed Central PMCID: PMC4602275.

Supplementary 1:

Disclaimer - this is not medical advice on how to treat gout, but my personal experience.  See your personal physician if you think that you may have gout or any type of arthritis.

I have had a lot of personal experience with gout since medical school. That is where I experienced my first gout attack.  I was up cramming for a Pathology test, eventually went to bed and was awakened at 3AM with intense left ankle pain. People have various descriptions for gout pain.  The one I have settled on is that it feels like your foot is being burned off with a blowtorch. The pain and inflammation are so intense that I end up feeling physically ill for days until the acute episode resolves. That first time I went the ED of the county hospital affiliated with my medical school. I was there for about 8 hours and at some point, the Orthopedic surgery team came by and aspirated my ankle joint between trauma surgeries.  They also asked my wife to leave the room and asked me if there was any chance that I had contracted gonorrhea -  another cause of acute arthritis.  I was given a prescription for acetaminophen with codeine and discharged home. Acetaminophen with codeine is not an anti-inflammatory medication and it does not treat gout – so the acute episode basically resolved on its own after a few days.

I was lucky enough to have gone to a medical school where the head of Medicine was a Rheumatologist who ran a lab that analyzed joint aspirates. I got in to see one of his associates and the diagnosis was confirmed based on that sample. That was after several visits to the Orthopedic surgery clinic where may leg had been casted in a splint for a presumed traumatic injury that I could not recall.

Over the intervening 30+ years, I would estimate that I have had about 20 attacks, 5 of them severe. In that time, I saw one excellent Rheumatologist who told me that given the fact that I do not have hyperuricemia or secondary manifestations of gout (tophi, nephrolithiasis) – I could treat the episodes symptomatically as they occur. Over the years that has been a moving target. A few of the regimens have been:

1. Indomethacin 50 mg TID for acute attacks.

2. Prednisone 60 mg/day x 5 days.

3. Prednisone 40 mg/day x 5 days.

4. Prednisone 40 mg/day x 5 days then 20 mg/day x 5 days then 10 mg/day x 5 days then 5 mg/day x 5 days.

5. Naproxen 250-500 mg BID for acute attacks

6. Vioxx (rofecoxib) 25-50 mg/day for acute attacks. Vioxx was taken off the market for cardiovascular and cerebrovascular side effects.

7. Colchicine – tried briefly and could not tolerate.

It should be apparent that seeing 10 different doctors for gout results in 10 different prescriptions. I can say that in my case, I do not tolerate high dose prednisone very well for even brief periods of time and that 20 mg will terminate an acute attack of gout within hours. The short course of prednisone always result in a flare-up of the primary attack and a tapering course of 15-20 days is usually needed, especially if that physician advises to not use prednisone and NSAIDS at the same time. My current goal is to get off of prednisone as soon as possible and on to naproxen.

The diagnostic problems with gout have also led to several misadventures. I recall being seen by a primary care MD who I had never seen before for acute wrist pain that was probable gout.  He insisted on inserting a needle into my right radiocarpal joint, even though I told him I had a diagnosis of gout by one of the top experts in the world at the time.  He ended up aspirating a piece of the joint capsule, instead. I have also had gout of the wrist and ankle misdiagnosed as cellulitis, even though I told that physician this was gout and I had a longstanding diagnosis of gout.

People tend to attribute the tremendous physician variation in diagnostic processes and treatments in complex polygenic illnesses to the “art of medicine.” I have always considered that an inaccurate phrase. I don’t consider anything about medicine to be artsy. Medicine including psychiatry is a technical field and physicians need to know technical details. The variation is accounted for in biological complexity that adds to the varied presentations of illness and the selection of treatments along a continuum from being very effective to not so effective for a particular person.

I also wanted to add a bit about the genetic approaches to illnesses especially the one mentioned in reference 8.  Today it is possible to search your own DNA for genotypes that are found in the literature to correlate with illnesses.  When I did that for the candidate gene for gout mentioned in the paper,  I found that I have the rs10889677 SNP with a C/C genotype on the IL23R gene on Chromosome 1.   According to this paper that may better explain why I am bothered with gout than the steady state of uric acid flux in my body.  My uric acid levels are always normal.

So much for what you learn in medical school.


Supplementary 2:

Total ICD-10 Gout Diagnoses

Total ICD-10 Mood Disorder Diagnoses

And you thought the DSM had too many diagnoses?


Attribution:

1:  The diagram on factors affecting the reabsorption and secretion of uric acid is form: Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10. (reference 7) and posted here per the conditions of their open access license.

Medicine to Psychiatry to Parking Lot: The Evolution Of Detox Over The Past 30 years

There is probably no better indicator of discriminatory rationing in the business run era of health care than the way substance users, alcoholics, and addicts are treated.  If you think about it - this is the ideal population to discriminate against.  In the severe situations where hospital detoxification is needed most of these folks are isolated and they have burned a lot of bridges.  They don't have a lot of friends and family members advocating for medical resources.  Most are unconcerned about their own health and many have significant medical morbidity associated with the addiction.  With any addiction, the tendency to continue the addicted states governs decision making so they enthusiastically leave medical facilities without addressing the problem as soon as a physician gives them clearance to go.  They are quite happy to keep bed occupancy and length of stay to the very minimum.  That is if they get admitted at all these days.

Back when I was in training as a medical student, I was fortunate to get most of my clinical training in large public facilities like county hospitals or VA hospitals.  In those days, patients with alcoholism or addictions who needed detoxification were admitted to Internal Medicine Services.  This was a great idea for several reasons.  Many people with addictions have significant medical comorbidity either independent of the addiction or due to it.  I saw many cases of acute pneumonia, pneumonia and meningitis, acute hepatitis, cirrhosis, pancreatitis, hepatic encephalopathy, delirium tremens, withdrawal seizures, and Wernicke's encephalopathy.  I don't think there is any better place in a hospital to address those problems than under the care of Internal Medicine specialists.  Until you have seen enough people critically ill and in withdrawal - it is difficult to appreciate the life-threatening aspects of intoxication or withdrawal from an addictive substance.  At some point in the mid to late 1980s, the detoxification landscape changed dramatically.  Suddenly a large number of those patients needing detox were sent to psychiatry services.  Only the obviously ill and delirious could get admitted to Medicine.  After the triage decision in the Emergency Department (ED) it was up to Psychiatry to sort out the problems and treat them as well as doing the detoxification.  There was also the development of county detox units, basically as a safer environment than the street, but offering little to no medical detoxification services.  If a patient went to a county detox unit and had a seizure there or became delirious - they could always be sent back to the ED.

A few years into my inpatient career. utilization reviewers started to deny the cost of care for anyone on my unit getting detox services.  That included people with the highest risk profile - depression, alcoholism, and suicidal ideation or behavior.  The primary rationale of these reviewers was that the patient did not require detoxification on an inpatient unit - even if they were in active withdrawal, taking high doses of detox medications, and had been discovered attempting suicide prior to admission.  The denial was based on an addiction or alcoholism and the fact that managed care companies had mandated that it was no longer an acceptable reason to treat somebody in a hospital.  The year was about 1990 and it was clear that this was a blanket denial of anyone with an addiction.  That had the predictable effect of inpatient psychiatry no longer being a resource for safe medical detoxification.  We are still dealing with the fallout from these business decisions 26 years later.  The fallout takes several forms including:

1.  A loss of infrastructure - there are no longer a significant number of Internists or Psychiatrists who routinely diagnose and treat withdrawal states and the associated addictions.  Most hospitals in any state do not have these services with the exception of the occasional person who is agitated or delirious in the ED and requires intubation and ICU support.  One of the frequent suggestions I hear about the current opioid epidemic is whether or not physicians are adequately trained in addictions.  With the loss of a detoxification infrastructure, I doubt that medical students and residents are seeing anywhere near the number of patients with addictions that they need to see relative to 30 years ago.

2.  A proliferation of inadequate detoxification facilities - a lot of the current facilities are run by counties and there is no medical aspect to treatment.  Decisions to get medical assistance may be made by someone with no medical background.  These facilities do not have environments that are managed to provide a calm and non-threatening atmosphere.  Many people admitted to them are fearful of the other patients and see the detoxification as a penalty.  They leave as soon as possible - even if they are still experiencing withdrawal symptoms.  Some of the facilities will only accept patients with a positive blood alcohol level by breathalyzer, and they discharge people when their estimated blood alcohol content reaches a certain level.  If you need detoxification from a sedative hypnotic or an opioid or several compounds -  you are out of luck.

City and county jails also double as detox facilities, in the same way that they double as psychiatric hospitals.  A common history is a patient on methadone or buprenorphine maintenance who is incarcerated, not given their usual maintenance medications and who is forced to go into acute withdrawal.  People who have been taking sedative hypnotics or using alcohol can also go into acute withdrawal that is potentially more serious.  Correctional facilities need systems in place to assure adequate and safe care for incarcerated individuals to prevent these acute withdrawal syndromes.  There are always a number of people with alcohol and drug use problems who die while they are incarcerated and as far as I can tell - these deaths are never investigated to determine if they received adequate medical and psychiatric care.

3.  A proliferation of "outpatient detox" - I can't really pinpoint when it became acceptable for patients with uncontrolled alcohol or drug use to suddenly manage their own detoxification using addictive drugs, but it is a common scenario these days.  Go into the ED with alcohol withdrawal and leave with a benzodiazepine to take on a scheduled basis.  Nobody should be too surprised if that medication is ingested at a higher than directed rate.  At times the entire bottle is taken on day 1.

4.  A disrupted spectrum of addiction care - apart from preventing life-threatening complications, the main reason for detoxification is to disrupt the cycle of addiction so that the affected person can get past all of the negative reinforcement (cravings, preoccupation, physical withdrawal symptoms) that keep the addiction going.  Without this modality, people are at home trying to cautiously taper off a drug or alcohol.  Many will go on for years without any success and they will be frustrated by the lack of abstinence or sobriety and give up.  Some with leave a clinic or ED with a supply of medication in order to try to detoxify themselves and realize that they are not able to take that medication on the suggested schedule to complete a safe detox.  Many will feel guilty or ashamed about going to AA or NA meetings while they are still using drugs or alcohol and give up.  Adequate detox avoids all of these problems with a rapid and safe approach to the initial stage of recovery from addiction.  

5.  The myth that business managers know what is best - the managerial class in America continues to run medicine without any knowledge of measurement, statistics, or quality.  In this case the logic seems obviously wrong.  Since the need for medical detoxification is an emergency it should be difficult to deny coverage for this condition.  That denial has been more or less routine and the cumulative denial has led to a serious degradation of services available for alcohol and drug use problems.

When I think about how medical treatment is supposed to work, every health plan should have adequate residential or hospital detox services for quality, safety and continuity of care.  Those facilities need to be more than holding tanks.  The environment has to be respectful, quiet, and comfortable where every patient feels safe and like they are being provided adequate care.  Active psychiatric consultation needs to occur because of the high comorbidity of psychiatric problems with addiction.  The current opioid epidemic has precipitated a discussion of improving the infrastructure to treat addiction.  That would not be too difficult since a large part of that infrastructure has been rationed out of existence in the last 20 years.

This sequence of events also has implications for all of the ideas about mandated physician education about opioid prescribing.  In some states the requirement is extensive and in many at this point it is mandated for licensure.  These mandates are shortsighted without the necessary infrastructure.  Addiction and detox services require administrative support and not administrative rationing.  Mandated education for physicians in not likely to do much good as long as they are sending addicted patients out with a bottle of medications and they end up detoxing in the parking lot.

It is time to drastically improve the treatment of all patients with alcohol and substance use disorders and stop the long-standing discrimination against them.      


George Dawson, MD, DFAPA

Closing In On Retirement

A happy retirement dream:  I am walking along the edge of a canyon that I have walked many times before.  In physical reality this canyon does not exist.  There is a large herd of buffalo stampeding through the canyon and making a lot of noise.  On the opposing ridge there are 5 or 6 wolves trailing the herd.  I see a family to my right and step into their yard to warn them about the wolves.  The father reassures me that everything is under control and there is nothing to worry about.  He has three small children playing behind him.  He introduces me to a friend who I recognize from college and who has not aged well.  I am sure that I remember his name but don't say it just in case I am mistaken.  I realize that I am late and need to take a test, but it is a long way back to town.  I think about asking my brother to pick me up and take me there - but I am already 15 minutes late.....


Closing in on retirement is not what I expected.  I can remember sitting in 8th grade English class and wondering what it would be like to live to the old age of 40.  Now that I am well past that and surprisingly healthy what is the best way to transition?  Many people who retire these days are in a similar position. Chronic illnesses are better managed and most people anticipate a phase of active retirement, before moving on to less activity.  One of the critical questions is how to make that transition as a professional.  Besides feeling fairly healthy and fit, I also feel like I am at the top of my game as a psychiatrist.  At a time when most psychiatrists are over the age of 55, should I try for a more gradual transition from patient care and teaching?  Or should I just walk away?  A lot of people seem to think that they have the answer.  They have observed my work habits that included too many hours and too few compromises and have concluded "You will never retire!"  The psychiatric colleague who I have known the longest has concluded that about herself.  She thinks that she will end up being  carted away some day from the job that she has worked for decades.  I know I could not do that because I walked away from that setting 6 years ago - burned out and fully intending to call it quits.  When you work a job for 22 years, it is easy to lose sight of the fact that there are many more reasonable jobs out there.  Some of us just hunker down in longevity mode and don't see it until a crisis hits.

I put some preliminary communications out there.  I concluded a couple of years ago that the most rewarding and efficient use of my time would be teaching - preferably psychiatric residents.  Residency programs are much different today than when I was a resident.  Business management has basically corrupted them.  Today it is virtually impossible to be teaching clinical faculty anywhere and not have the same productivity expectations as psychiatrists in private practice.  In other words there is the expectation that you can see large numbers of patients and continue be an innovative and creative teacher.  Your salary is "justified" by the amount of billing that is generated.  That has never really worked for me.  I just attached one of my old storage devices to my current network this afternoon.  Sitting there on that drive was a series of 10 PowerPoints on psychopharmacology from 2008.  They were all 2 hour lectures and I came up with them from scratch after meeting with the residency director of a program I was affiliated with.  The residents that year had requested that I teach the psychopharmacology lectures.  I had peripheral involvement with the program until that point - largely due to the administrative restrictions.  She thought it was really important for me to do it and I agreed that I would, but it was a significant time penalty for me.  There was no productivity credit for preparing and delivering the lectures and no additional reimbursement.  It was all done on my own time after taking care of all of the clinical work, billing and documentation.  All done late at night and on the weekends - free gratis.  Despite that, I was confident that I did a good job and the residents appreciated the work.

The point I am at in psychiatry, I am confident that I can teach nearly anything and do a good job of it.  I am not confident at all that I want to transition into retirement seeing 75 - 100 very ill polypharmacy patients and teaching residents how to tweak that polypharmacy.  You really don't need an experienced and knowledgeable psychiatrist to do that.  I know that this is not really psychiatry, but somebody's business model of how to generate revenue and not consider all of the information that merits consideration.  I can't sit by and look at people who have never had a manic episode being misdiagnosed with bipolar disorder, or the endless people with chronic stress in their lives expecting that medication will somehow change that, or the high functioning person with "ADHD" who really wants a prescription for a stimulant so they are not at a competitive disadvantage in college or professional school.  Beyond that - I can't bite my tongue and listen to how they are seeing a therapist who is a "sounding board" and endlessly rehashing either their childhood or what happened last week and how that is supposed to be productive psychotherapy.  I can tell them what they need to do to get better and if necessary do the therapy myself.  And then there are the people with non-epileptic seizures, psychogenic mutism, chronic Lyme's disease, chronic pain, chronic daily headaches, reflex sympathetic dystrophy/complex regional pain syndrome and endless somatic permutations that need psychiatric care but walk in saying they don't: "I am here because my doctor thinks this is all in my head".  There are the people with delirium, dementia, movement disorders, and abnormal MRI scans.  I can see all of those people until my dying day, but it does not make an impact unless what I know can be amplified through current residents.

Before business managers ran medicine there was the kind of room I need at the current stage of life.  Senior staff in those days were the people the house staff and attendings consulted.  The absolute best teaching team that I ever worked on was a Nephrology team at Froedtert Hospital in Milwaukee.  It was my last rotation in medical school.  I recall finishing rounds at 10:30PM on the night before graduation and walking across the county hospital grounds to my apartment like it was yesterday.  That team was staffed by two senior Nephrologists in their late 60s.  The remaining team members included a Nephrology Fellow, two internal medicine residents, an intern and me.  There was no myth that these senior staff somehow knew less or were less relevant.  It was quite the opposite.  We rounded twice a day until all of the consults and hospitalized patients were covered and the senior staff were the primary discussants.  That myth is alive and well today, largely as a means to disenfranchise the tested clinical methods in medicine and make future generations of physicians dependent on organizations run by business managers rather than colleagues.  Organizations that have promoted the idea that tests and arbitrary and unvalidated performance metrics are more important than spending enough time with patients and enough time discussing clinical scenarios with a broad range of physicians including the most experienced colleagues.  It is no coincidence that the myth thrives in non-academic hospital environments staffed by generalists working impossible shifts.  Knowledge and academics seems at its leanest point in the past 50 years.  

At this point I am resigned to do what I can.  I have offered my services but there are a significant number of reasons why none of that may come to pass.  The hardest thing about retirement for me comes down to three issues.  First, there are not nearly enough people to take my place.  Psychiatry is possibly the best example of how a field can be decimated by political and business influences even in the midst an obvious shortage of services.  Throughout my entire career there has been a shortage of psychiatrists and nobody has done a thing about it.  Second, the very inefficient transfer of knowledge.  I was personally taken out of the teaching loop for a long time by business practices that made it impossible for me to teach.  What I know is not written down in texts and if I don't pass it along - it dies with me.  That is counter to the evolution of how knowledge is passed from one generation to the next.  Only American politics and business practices can stop evolution in its tracks.  Finally, being an active part of a person's treatment and recovery from mental illness is important to me.  In every case that involves an internal process on the part of the psychiatrist.  In retrospect, I have attributed it to having great teachers and colleagues, a great memory, a particular personality characteristic, scholarship, or just being compulsive.

Despite what the measurement based people say, the validation of that process is totally subjective.  At the end of the day or years/decades later - it is a person saying that you made a difference in their life and knowing that happened because you gave them the best medical advice that you could at the time.  For me personally, it has also meant seeing people who have the most severe problems.

I won't miss any of the productivity based work any more than if I walked off any assembly line.




George Dawson, MD,  DFAPA




Addendum: 

I realized in the last couple of years that this blog factors into the transition as well.  People have always asked me how I know something when I quote research or suggest a particular treatment or method of analysis.  I think that part of what I am doing here on these pages is illustrating how I know something.  Hopefully fellow psychiatrists, but especially medical students and residents will find it useful.


Attribution:

The graphic at the top of this post was downloaded from Shutterstock on July 4, 2016.











               

Modern Medical Management - The Myth of Sharing

Any casual reader of this blog will note that I don't really find any value in the myriad of management practices that have been added to medicine since businessmen and their friends in government have taken over.  The only reasons that these practices have been added is strictly political and rhetorical.  Nothing has been overhyped as much as management adding value to medicine with so few results.  Nothing has done quite as much to detract from the quality of care than these same business practices.  At this point they have become as entrenched as gun legislation and will be every bit as intractable. These problems are very difficult for the typical consumer/patient to see.  The obvious points of contention are insurance company denials either for medication or medical care.  They peaked in the 1990s when managed care companies thought that they would just put specialists out of business and had primary care physicians acting as "gatekeepers".  If you are old enough you may recall having to get a referral from your primary care physician to see specialists, for various services. and in some cases even to go into an emergency department.  It took them a while but these businesses learned that being that transparent in denying care was probably not in their best interest.  It also created a large burden on primary care physicians who were now uncompensated reviewers for the insurance company business practcies.  Eventually that system was scrapped in favor of shifting financial risk around - some to consumers and some to physicians and physician groups.  There are many ways it can happen, I thought I would provide a few examples below.

Managers like to use a shared decision making model in their manipulation of physicians.  I guess they don't consider physicians to be particularly bright people.  I don't know if that happens when you are socialized in the business world and automatically consider your decisions to be the best based on scant data, a lack of measurement standards and perceived quality of a good idea.  Whatever the reason, the approach generally only works because the physicians have no leverage.  Consider the following example.  Ten physicians are in a group providing hospital coverage for admissions to a community hospital.  It can be any specialty.  They are working a 7 days on and 7 days off model and each of them typically admits 10-14 patients per day at work.  They are stretched to the maximum so that anyone requiring emergency leave seriously disrupts the schedule.  Their colleagues are expected to cover.   The administration would like to open an 10% additional bed capacity and meets with all of the physicians about this to problem solve over how that might happen.  The physicians are asked the question: "We are here to all figure out how to increase the number of admissions by 10%.  Do you have any ideas about that?"  That leads to a general discussion of how the physicians are overworked and already spending too much time from home on the electronic health record.  A consensus builds and the physicians say they need more staff and staff to cover unpredicted absences.  At that point the administrator states: "No - I guess I didn't explain myself very well.  We are here to decide how to provide more services without increasing the cost by hiring new people."  The physicians finally get it.  Sharing in this case means, I will ask you for your input, but it is meaningless and I will require that you work harder even though you are probably burned out right now.

Another popular sharing model where physicians share more than anybody else is financial risk sharing.  The first introduction was when RVU productivity units were introduced.  The initial administrative argument seemed to be that not everyone was carrying their own weight.  The RVU system was portrayed as being inherently more advantageous to those people who were really productive.  It would allow them to make more more than the slackers in the department.  That was a good theory to try to appeal to physicians competitive natures, but in most departments - schedules and productivity was already saturated.  There were no slackers.  That point goes to the administrators.  The second risk sharing introduced was the "holdback" model.  This said that 10-15% of everyones' productivity would be held back until it could be assured that the production figures were met and then it would be released to the physicians in the group.  Keep in mind this was money that was already billed and earned.  There was no similar "holdback" from administrators or other personnel.  A take off on this risk sharing was getting physicians in administrative meetings and showing them endless spreadsheets of overhead costs and how much they would have to "produce" in order to get either their holdback or some other form of reimbursement.

The ultimate form of risk sharing today seems to be the contract that comes in and puts everyone at risk by not even recognizing the physician billing.  In this case the insurer comes in and says - this is how much we will pay you on a per diem basis to cover these patients for various problems.  You agree not to charge use anymore than than - no matter how much care each one of those patients needs.  This last model is the most insidious.  It caps any insurance payments (losses) and puts any physicians and their clinic at complete risk for catastrophic loss but more importantly it is a war of attrition.  With this model as the only source of funding, it allows administrators to view physicians as "costs" rather than resources and eliminate them, underfund them, overwork them, and burn them out.  It is a tried and true pathway for how managed care organizations using this model can adversely impact the quality of care in every organization they contract with, but especially the ones that don't understand corporate doublespeak.

Too many of my colleagues tolerate corporate doublespeak in management systems.  They don't seem to understand that risk sharing does not really mean that anything is shared.  It means that they are left holding the bag.  These same systems tell us how "younger physicians" are more accepting of these models.  Medical professional organizations and specialty boards are talking the talk.  We have the American Psychiatric Association talking about various collaborative care models where psychiatrists don't need to see patients any more.  The speciality boards have designed a number of expensive and complicated performance metrics that have no basis in reality and CMS (Centers for Medicare and Medicaid Services) has done the same.  It is hard to imagine that when I started out in Medicine we did not have to deal with all of this administrative fantasy.  We went to work each day and it centered on the facts, patient care, and the medical science of the day -

Not what somebody forced us to believe for a few months at a time while they were wasting our time, energy, and money.

  

George Dawson, MD, DFAPA

The Demise of the "5th Vital Sign"

The American Medical Association came out two days ago and said that they were dropping the pain as the fifth vital sign movement because it encouraged opioid overprescribing.  Even more interesting is that I did not get the news from the AMA (I am a 30 year member) but from the Pain News Network.  The only stories that I could Google the next day was about the AMA defending its position against attacks from pain societies and organizations who want to maintain what I would describe as a liberal approach to opioid prescribing as the best way to approach pain.  My term liberal is meant to connote a political position with no basis in science and the lack of science started in 1998 with the pain as a 5th vital sign approach.  In 1996, the President of the American Pain Society declared pain as the Fifth Vital Sign.  In the year 2000, the Joint Commission (then JCAHO) launched a pain initiative that described the 10 point pain scale as a "quantitative approach to pain."

I don't know if quantitative analysis is still a prerequisite for medical school, but this is a reason why it still should be.  In quantitative analysis, the task is to measure chemical concentrations accurately and reproducibly.  To use a quote from my old analytical chemistry text (1): "Qualitative analysis is concerned with what is present, quantitative analysis with how much is present."  The ability to do this is often a major part of the grade for that course.  Since the chemical composition in the samples are known - they should be determinable with precision.  In some cases, a lack of accuracy can reflect problems with the analytical technique if there are widespread variations in the results.  This is a true quantitative approach.  Asking a person to rate their pain on a 10-point scale is not.  Pain is a subjective experience influenced by a number of variables including whether the pain is acute or chronic, emotional state, the presence of an addiction, and personal biology affecting pain perception.  It is not a quantitative assessment.  It is as obvious as asking someone where they are on the 10-point  scale and being told they are a "14".  There are a lot of potential messages with that statement, but none of them involve an accurate measurement of pain.  A quantitative scale has no implicit meaning - it is supposed to be a known measurable quantity no matter what.

From a medical perspective, there is also no better example of the adverse consequences of widespread screening for a problem.  Chronic pain varies with age and other demographic factors.  Epidemiological surveys show widely variable numbers of people with chronic pain, but some suggest an average is about 25% of the population and 10% of the population with pain that has some secondary disability.  While there are no good ways to estimate the optimal amount of opioid needed to treat pain in a population, current data suggests that the US is the largest consumer of prescription opioid drugs in the world.  For example, the US has 5% of the world's population and Americans use 55% of the world's supply morphine and 37% of the world supply of fentanyl.  By contrast 80% of the world population uses 9.9% of the morphine and 19.7% of the world's fentanyl.    The United States is clearly at the top in terms of opioid consumption.

Clinical trials have also shown that opioids are moderately effective for some forms of chronic pain and no more effective than non-opioid medications.  The screening approach to chronic pain is clearly associated with overexposure to opioids, widespread availability of illicit sources of opioids, and an epidemic of overdose deaths.  The idea that rapid assessments can be made with rapid qualitative screening by anyone also eliminated pain specialists as gatekeepers in the decisions about who would receive treatment with opioids for chronic noncancer pain.

In the opening days since the AMA statement, it appears that political forces are lining up to maintain the status quo.  The idea that the AMA has to defend their position seems like pure rhetoric to me.  How about the American Pain Society defending the original statement in the context of everything that has happened since?  Despite defensive statements about how opioid prescribing was increasing before the position was adopted - the hard data suggests that it was associated with a major inflection point in opioid consumption in the USA.

The policy debate on this simple statement has far reaching effects for health policy in the United States.  At every level in today's health care system there are groups of managers/administrators who have set themselves up to monitor various measurements and hold somebody accountable.  I doubt that they know the difference between quantitative or qualitative measurements any more than the people who proposed that a subjective pain scale was somehow a quantitative measure.

I doubt that any one of them ever took a class in Quantitative Analytical Chemistry.



George Dawson, MD, DFAPA



References:

1:  James S. Fritz and George H. Schenk.  Quantitative Analytical Chemistry. Second Edition.  Copyright 1969 by Allyn and Bacon, Boston, p 3.



Attribution:

Pain scale graphic downloaded from Shutterstock per their standard license on June 29. 2016.

Free Lunch and Odds Ratios - The Rest Of The Story

JAMA Internal Medicine came out with an article this week that has been heavily covered by most media outlets.  The Wall Street Journal headline was: "Even Cheap Meals Influence Doctor's Drug Prescriptions, Study Suggests".   Time concludes: "Why Doctors and Drug Companies Can't Be Friends".  Even public radio got into the act with "Crestor Prescriptions Rise After Doctors Get Free Meals."  It is pretty clear that in the court of public media that Big Pharma is at it again, bribing doctors into using their drugs and the most expensive drugs at that.  But is that really what the article suggests?

Even a casual reader could hone in on the discussion session of the article and read the following about cross sectional data and disclaimers about causation versus correlation:

"Our data are cross-sectional. The findings reflect an association, and not necessarily causality. Because we linked 5 months of Open Payments data with 1 year of Medicare Part D prescription data, we also could not determine whether high prescription rates for brand-name drugs were preceded, followed, or temporally unrelated to the receipt of industry-sponsored meals.  The policy implications of our findings thus depend on further clarification of the mechanism of the association between the receipt of industry-sponsored meals and physician prescribing behavior..."

Two additional paragraphs of study limitations follow that clearly show that this initial look at this data has significant limitations.

Various blogs and sites have picked up on this paper as well many of the physician sites also seem to favor the narrow interpretation as seen in the press.  In some cases there is a nod to the theoretical issue of causality but a discussion of the result as though it is proof of something.  I can think of a number of competing theories that should be tested instead of the meal equals causality theory but do we even have to go there?  Bear with me on the analysis here.

Looking at the basic design of this study, the authors looked at a database of 533, 919 prescribers in the Medicare Part D database.  252,250 of these prescribers were eliminated for administrative reasons that can be examined in the Supplemental section of this paper.  From there the authors determined which of these physicians wrote 20 more more prescriptions for the four study drugs of interest -  statins, cardioselective beta blockers, ACEI or ARB antihypertensive prescriptions, or SSRI or SNRI antidepressant prescriptions.  Table 2 in the final paper shows the total prescribers and their characteristics in each group.  The total number of physicians receiving financial reimbursement varies from 2-12%.  That reimbursement totaled 63,524 payments totaling $1.4 million - 95% of which was meals and 5% in the form of other promotions.  The meals averaged $12-18.  The authors proceed to show that the sample selected for reimbursement were more likely to prescribe the promoted drug.  They do this by calculating the odds ratio of prescribing versus the non-reimbursed physicians.  They also calculate the odds ratio across a number of variables including the number of day (0 -> 4+) in order to demonstrate a dose response effect of the promotions on prescribing and conclude that industry sponsored meals was associated with an increased rate of prescribing the name brand drug in each class that is being promoted.

The standard response to this study seems to be: "Aha - no news there.  We knew that Big Pharma corrupts physicians and even the slightest gift sways prescribing practices."  I will let the reader pull up the article and read the authors concerns about causality.  I don't think that predictable corruption or an esoteric statistical argument about causality is the most interesting part of this paper.  I think the most interesting part of this paper has apparently been lost on the majority of people reading it.  Let me put it another way.  Would it shock anyone that a small (2-12%) proportion of physicians, carefully selected for whether or not they accept promotions from pharmaceutical companies end up prescribing the promoted drugs more frequently than physicians who don't?  I don't think that it should.

The good news in this article is that 88-98% of the physicians studied apparently do not accept these promotions and by the authors definition do not prescribe the promoted drug at anywhere near the frequency of the studied group.  The majority of physicians do prescribe promoted drugs, even without receiving any incentive from the pharmaceutical company and that should also not come as a shock to anyone.  As a former member of two Pharmacy and Therapeutics (P&T) Committees, I can say unequivocally that all members of a generic class are not equivalent when applied to any population of human beings.  Response and tolerability vary significantly from person to person.  In the case of generic antidepressants - SSRI/SNRI are all commonly used as first line drugs primarily to avoid prior authorization harassment of the prescribing physician.  There are many patients who fail several and many patients who cannot tolerate any of these medications.  In those cases non-generic medications are often the next choices.

Any time I see a statistic like an odds ratio, I tend to interpret it like percentages.  Those numbers seldom stand on their own.  There needs to be some additional data.  In the table below, I show the number of prescribers in each category across all 4 classes of research drugs and the Target Drug used to calculate the odds rations.  It is clear that the vast number of prescribers in each class are in the No Meal (NM) category.  It is also clear that the prescribers in the Meal (M) category prescribe the drug class at a much higher rate than their NM colleagues.  Even if the prescribing rates in the M category are relatively high, it is easy to speculate that the total prescriptions for the target drugs may actually be higher in the NM category despite the odds ratios indicating that the M physicians are more likely to prescribe them.  I sent an e-mail to the corresponding author on this issue and asked for the raw data as rates of target drug prescribing in each group or the raw numbers for all of the target and non-target drug prescriptions in each class.  I will post those results here if I receive them.

Class/ Target Drug	Meal =M No Meal =NM	Average Rx Volume Per Prescriber	Total Prescribers
statin/ rosuvastatin	M	742.2	15,941
	NM	470.1	115,266
beta blocker/ nebivolol	M	410.0	3843
	NM	299.8	122,291
ACEI/ARB/ olmesartan	M	562.7	9483
	NM	394.8	121,860
SSRI/SNRI/ desvenlafaxine	M	437.6	1926
	NM	289.5	121,392

Just looking at total prescriptions in any class the NM physicians prescribe roughly 5 times the total of the 4 general classes of medications as those who are designated as M prescribers.  Pharmaceutical companies are clearly selling these medications without the suggested promotion.    This is a better measure of the impact of pharmaceutical promotions and it illustrates the fact that there are other significant forces at play than a free lunch.

Overall I thought this paper was useful because it provided confirmation of one of my previous observations on pharmaceutical pricing.  In that post I made the statement that even when physicians are taken out of the promotion loop by one force or another, the United States still has by far the most expensive pharmaceuticals.  This paper provides proof that the vast majority of physicians are not getting the free lunch promotions and contrary to most of the headlines don't base their prescribing on an inexpensive meal.  Although we currently do not have a good characterization of what the real difference in target drug prescriptions is between N/NM groups it is safe to say that there is more at play here than an $18-20 meal.

That fact alone suggests causation is more complex than it seems in the papers.



George Dawson, MD, DFAPA


Reference:

1:  DeJong C, Aguilar T, Tseng CW, Lin GA, Boscardin WJ, Dudley RA. Pharmaceutical Industry-Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries. JAMA Intern Med. 2016 Jun 20. doi: 10.1001/jamainternmed.2016.2765. [Epub ahead of print] PubMed PMID: 27322350. (free full text online).

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