Hutterite Dust versus Amish Dust

From previous posts, I consider asthma to be a good comparison illness with mental illnesses for a number of reasons.  The diagnosis is frequently unclear.  There are no specific diagnostic tests for asthma.  Attending even a state of the art clinic for asthma usually consists at some point of filling out a subjective checklist of symptoms and disability - including the frequency that a rescue inhaler is used.  The majority of asthmatics are symptomatic with wheezing.  The symptomatic state is often considered a sign of compliance with treatment measures, but the reality is that asthma is difficult to treat and there is a strong environmental component to treating it.  Depending on the physician, environmental engineering like air filters, dust removal, and avoidance of certain allergens is typically discussed but less often than in the past.  The mainstay of treatment is corticosteroid inhalers with long acting beta agonists where the corticosteroid inhaler alone is not enough.  Some authors have defined endophenotypes that may represent different disease mechanisms.  The overall prevalence of asthma has increased significantly suggesting an environmental component.

Additional epidemiology has shown that exposure to high microbial environments such as livestock exposure on traditional farms confers some protection in terms of the development of asthma.  The Amish are noted to have a decreased rate of asthma and allergic sensitization than non-farmers.  These factors led to a very interesting study in this week's New England Journal of Medicine.  In this study the authors elected to compare schoolchildren from both Amish and Hutterite families on a number of genetic and immunologic markers.  Sixty children were studied from both communities.  They were sex and age matched to within one year.  Half of the children were from an Amish community and half from a Hutterite community.  Both groups are from a similar European geography and on an SNP analysis of genetic association were strikingly similar in terms of comparison groups.  The main environmental variable was that the Amish farms were single family dairy farms and the Hutterite farms were communal mechanized farms.   Previous reports had determined that the Hutterite children had a higher prevalence of asthma (21.3% versus 5.2%) and allergic sensitization (33.3% versus 7.2%) than the Amish children.

Blood tests were done on the children to determine immune markers.  The Hutterite group had higher levels of IgE to common antigens.  The Hutterite children also had increased eosinophils, decreased neutrophils and about the same number of monocytes as the Amish children.  Blood samples were screened for 26 cytokines and 23 were found.  Median cytokine levels of each were higher in the Hutterite group even when the known asthmatics were excluded (there were no asthmatics in the Amish group).  Gene expression profiles were also generated for all of the subjects and pathway analysis was done with a standard informatics based approach.  From these analytics the authors concluded that the most significant module in both the Hutterite and Amish children contained 43 genes.  Eighteen of the genes resulting in overexpression of tumor necrosis factor (TNF) and and interferon regulatory factor 7 (IRF7) were present in the Amish children.  Both of these proteins are important in the innate response to microbial stimuli.  

The house dust experiment was conducted in a mouse model of asthma.  Dust extracts were administered intranasally over 4-5 weeks.  Hutterite dust produced airway hyperresponsiveness and eosinophilia in bronchoalveolar lavage specimens from the mice but the Amish dust did not.  Mice deficient in MyD88 and Trif - proteins required for innate immunity signaling (5a) did not respond to the inhibitory effects of Amish dust extract on airway hyperresponsiveness or eosinophilia as further evidence that innate immunity is involved.                          

The authors and the accompanying editorial by Chatila (2) emphasize the importance of this study.  Amish dust is able to activate innate immunity by very specific mechanisms that led to its protective effects against allergic sensitization and allergic asthma. The authors cite the main deficiencies of the study as not looking at children younger than 6, limited dust sampling, and a sampling strategy of asthmatics that resulted in a higher numbers of Hutterite children with asthma.  The editorial suggests that the dose of dust to prevent or possible moderate asthma is not really determined.

This was a very elegant study that has the potential to create novel therapies for an illness that is currently not very well treated.  It highlights that fact that polygenic illnesses, especially those representing complex systems and complex interacting systems are difficult to characterize but with modern methods of analysis we are getting closer.  It was not too long ago that many of the molecules listed in the diagrams at the top of this page were not known to exist.  The best example I can think of is the leukotrienes that were collectively known as Slow Reacting Substance of Anaphylaxis or SRS-A. (4).  Cytokines were also unknown.  The fact that all asthmatics are not alike and that some authors believe that clear endophenotypes exist suggests that in the genes and proteins mentioned in this article significant variation should be expected.  If these findings are accurate, it also points out the importance of slight differences in the environment in the development of asthma.          


George Dawson, MD, DFAPA


References:


1: Michelle M. Stein, B.S., Cara L. Hrusch, Ph.D., Justyna Gozdz, B.A., Catherine Igartua, B.S., Vadim Pivniouk, Ph.D., Sean E. Murray, B.S., Julie G. Ledford, Ph.D., Mauricius Marques dos Santos, B.S., Rebecca L. Anderson, M.S., Nervana Metwali, Ph.D., Julia W. Neilson, Ph.D., Raina M. Maier, Ph.D., Jack A. Gilbert, Ph.D., Mark Holbreich, M.D., Peter S. Thorne, Ph.D., Fernando D. Martinez, M.D., Erika von Mutius, M.D., Donata Vercelli, M.D., Carole Ober, Ph.D., and Anne I. Sperling, Ph.D. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children N Engl J Med 2016; 375:411-421; August 4, 2016; DOI: 10.1056/NEJMoa1508749

2:   Talal A. Chatila, M.D., M.Sc. Innate Immunity in Asthma. N Engl J Med 2016; 375:477-479; August 4, 2016;  DOI: 10.1056/NEJMe1607438.

3:  Chapter 2:  Innate Immunity in Peter Parham.  The Immune System, Third Edition.  Garland Science, Taylor and Francis Group, LLC.  New York.  2009.  pp 31-70.

4:  Roitt I.  Essential Immunology, Third Edition.  Blackwell Scientific Publications, Oxford. 1977, p 157.

5:  Links to Kyoto Encyclopedia of Genes and Genomes (KEGG):

a) KEGG (MyD88-3 and trif):  Link

                

b) Toll like receptor signaling:  Link

                

c) NF- Kappa B signaling:  Link

                

d) Innate immunity:  Link

                

e) Adaptive immunity:  Link

Attribution:

Both graphics at the top of this page are from VisiScience.com and posted per their user agreement.

Catastrophic Thinking About Catastrophes

A storm rolls into Minneapolis - photo by Eduardo Colón, MD

Like most psychiatrists, I have spent a lot of time listening to anxieties about hypotheticals.  Are people judging me when I am out in public?  Will I fail an examination?  Will I end up penniless and homeless?  Am I really dying of something that the doctors can't diagnose? Am I going to lose control and drive off a bridge on the way in to work?  Now that my relationship is over will I ever find another person who will love me?  The human mind is set up to obsess about the improbable and if you have the predisposition to create a hypervigilant approach to this anxious stream of consciousness it will lead to much less sleep and a number of physical symptoms.  Many  people have had these patterns of thoughts for years or decades before they decide to see a psychiatrist or a psychotherapist.  This kind of anxiety can be disabling even without any panic attacks or significant physical manifestations.  It is an outstanding example of how emotion impacts decisions - in this case the decision to worry about something that is recognized as illogical.   One of my standard questions of the anxious person involves catastrophizing or jumping to the worst possible conclusion.  It is also a universal human experience.  The best example is assuming the worst if a family member is late when driving over to your place.  Are they in a ditch?  Are they in the emergency room?  Have they been in an accident?  Are they dead?  Common thoughts that various people get in that situation.  When it comes to real catastrophes, the thought patterns change significantly.

I have always been interested in catastrophes - ever since I read a book as a kid about a meteor hitting earth.  In those days we used to have to go to a bookmobile stop, get on a large recreational vehicle that functioned as a mobile library and borrow books to read every week.  That book caught my eye, because it had a picture of the collision on the cover and a detailed description of events on the inside.  At the time, the real risk of massive destruction was a standoff between the US and the USSR in the Cuban missile blockade and a decision by a Soviet submarine commander - but taxpayers are always the last to know.  We were worried plenty about that real crisis, but at about the same time - I was reading my first 400 page novel on a meteor hitting earth and all of the destruction that would involve.  Over the years it has lead to a focus on how to survive, the unsurvivable,  I have referred to myself as a survivalist at times but realize the I am half joking.  Real survivalists tend to see catastrophic events as impacting on the food supply.  I have heard the credo that "We are only 5 meals away from chaos."  The associated strategies are food hoarding, secure locations, and plenty of firearms if necessary.  I think it is logical to think that the food supply may be constrained, in quantity and volume - but I think that is also logical to take an approach that involves that maximizes the survival of the human race - from anything just short of the destruction of the planet.

My personal involvement with disaster planning peaked about 8-10 years ago.  At that time I was involved in 2 avian influenza task forces - one localized to the hospital where I was working and the other metro and statewide.  An influenza pandemic is a very lethal event that can result in tens of millions of deaths.  The last time the world population was subjected to a highly lethal strain in 1918, people were going to work in the morning and dropping dead in the streets on the way home in the evening.  My participation in these task forces was highly instructive on a number of issues.  I was involved in teaching psychological first aid (PFA).  The theory was fairly simple.  Most people who suffer the psychological trauma of a mass event like an epidemic will recover psychologically.  The focus is reassurance, providing information, and preventing surges of activity in hospitals and emergency departments that would overwhelm resources.  That theory was based on what happened after the concern about anthrax being sent to the US Capitol building occurred.  In that event emergency department (ED) services were immediately overwhelmed by people who thought they were exposed to anthrax.  To prevent that - trained PFA staff would be in ED areas to assist with keeping people moving.  The unfortunate reality was that the real infrastructure, ventilators and isolation rooms would be almost immediately overwhelmed even with the appropriate surge protection.   Nobody had adequate infrastructure to treat high numbers of people with respiratory failure who were infected with a highly virulent strains of influenza virus.  Nobody was interested in building that infrastructure.  Nobody was interested in HVAC (heating, ventilating, air conditioning) systems that did more than isolate a few infected people.  There was an interest in getting oseltamivir phosphate (Tamiflu ®) to whoever needed it.  I saw a slide several times of large pallets of boxed oseltamivir sitting in a large government hangar somewhere and being told that it was ready to be shipped to whoever might need it.  There was also an interest in what to do with large numbers of dead bodies and fairly specific plans for that detail.  In the end, the only logical conclusion was that the planners of this event were fairly hopeless about the outcome and trying to quell either the expected mass hysteria, the inability to marshall any realistic resources, or both.  From what I have seen, I would not expect a better outcome than 1918, unless there are effective vaccines immediately available.    

Non-Biological catastrophes are broader in scope and potentially more devastating.  The recent overview by Julia Rosen in Science (1) illustrates the possibilities.  An interesting aspect of the non-biological catastrophes is that they necessary need some kind of a hard fix.  There needs to be a basic shelter or someone has to figure out how to go out into space and either destroy or displace that asteroid hurtling toward the Earth.  There is no imaginary hospital bed capacity like with a biological epidemic.  If you don't have a real shelter or a real intercept device - all or part of the human race perishes. According to Rosen,  even these scientists are subjected to a "pervasive giggle factor".  Many do not see the study and prevention of catastrophes as mainstream science.

The body of Rosen's article discusses natural events that can decimate the infrastructure and other that could lead to the extinction of humans.  An example of an event that is probably not directly harmful to humans is a coronal mass ejection (CME) from the sun.  High energy particles are ejected from the sun and into the Earth's magnetic field.  The particles can destroy power grids and other electrical transmission gear.  CME events have occurred on Earth, one of the largest in 1859 called the Carrington Event.  Any similar event today might place power transformers at risk and create widespread havoc with the power grid resulting in large section of continents going dark for as long as years.

Near-Earth Objects (NEOs) are a more clear danger and probably have the most scientific investigation.  The Spaceguard survey by NASA identified 90% of the NEOs larger than 1 kilometer by 2010.  They are currently working on identifying 90% of the NEOs greater than 140 meters by 2020.  No NEO identified so far is on a colleion course with Earth.  The article contains a graph of Damage/Fatalities versus Recurrence Period in Years for Volcanoes, Impacts, Earthquakes, Floods and Tsunamis.  According to that graphic - a global catastrophe from an NEO impact recurs about once in 100,000 years.  From the graphic below, that event would have been the eruption of Mt. Toba in Indonesia about 74.000 years ago.  That may have killed most humans and led to a bottleneck event in human evolution where climate change led to a rapid paring of certain populations and more rapid adaptive changes.  Interestingly some fossil evidence suggests that native people in the vicinity of the eruption survived it and adapted to it.  The 1980 Mt. St. Helen's eruption is shown for relative scale.  That event killed 57 people and covered 22,000 square miles.  At 10 miles the ash was 10 inches thick.         

Graphic From US Geological Survey - Public Domain

I took the above events and tried to order them chronologically in the following graph.  For comparison with human evolution the first ancient humans (Homo erectus, Homo heidelbergensis) started out in East Africa about 200,000 years ago and started to migrate north.  The evolutionary changes necessary for modern humans happened about 50,000-75,000 years ago - sometime after the Mt Toba eruption.  The fossil evidence from Mt. Toba suggests that a supervolcano eruption in Yellowstone is survivable.  The critical question is how?  Various scenario have suggested that the sulfur dioxide content in the air will lead to climate change and a much higher prevalence of pulmonary illness.  Climate change will likely be a problem.  Fossil evidence suggests that there was a decade long period of cooler drier weather after the Mt. Toba eruption.    Computer simulations of the ash distribution from a Yellowstone supervolcano event would cover most of a triangular area from Los Angeles to Chicago to Calgary would be covered in ash varying in depth from 40 inches or more at the center to about an inch at the periphery.  With volcanos there is also a significant environmental impact from both the direct blast and and toxic gases like sulfur dioxide.

Whenever I discuss some of the issues with friends or coworkers - I get the same nervous laughter mentioned in the Science article. People can't seem to believe that there is anyone out there thinking about these things. The endpoints of the spectrum include: "You are nuts!" at one end to "I am just going to run outside and stand under the mushroom cloud. I would rather be dead than living in my basement for a year." at the other.   These sentiments were captured by Cormac McCarthy in his post-apocalyptic novel The Road. In the novel a boy and his father wander a dangerous post-catastrophe countryside. The actual event is never specified but there is widespread famine, climate change, and primitive behaviors including constant confrontations about food and cannibalism. There are flashbacks about the wife and mother of this dyad and we learn that she was not able to cope with the new reality and committed suicide. At one point they encounter an old man along the road who wants some of their food. There is tension between the father and son - the father wants to move on and the son is still altruistic and wants to help the old man. At some point there is a conversation and the old man sums up the situation when asked if he tried to "get ready for it":

"What would you do?....Even if you knew what to do you wouldn't know what to do. You wouldn't know if you wanted to do it or not. Suppose you were the last one left? Suppose you did that to yourself?" (p168-169).

McCarthy does a masterful job of capturing the attitudes of the resilient, the hopeless, and the altruistic after a catastrophe. He also illustrates that in truly catastrophic conditions nihilism may be a logical conclusion, but hope still lives on in the minds of others.  I have encountered all of these attitudes in discussing the prospects for survival, but my anecdotal experience is that most of the people planning to survive seem to be planning on confrontations and shoot outs that are directly out of The Road.

I think the outcome can be much more positive, survival enhancing and optimal when it comes to the survival of the human race.  It does take a more enlightened approach to food and shelter. It requires generations of planning. It requires multidisciplinary planning to gradually change the infrastructure. I was not able to get a critical reference to complete this post that was listed in the Rosen article (5). This book has been widely reviewed as a possible solution when food storage is not possible. Their suggested food sources would be useful in any sun blocking catastrophe like a supervolcano, nuclear winter or high speed impact by an NEO where vegetation could not be grown. Gradual but large scale changes to the infrastructure could also result in permanent dwellings designed to provide fresh food and water to the occupants as well as waste disposal and HVAC systems that would function in a highly adverse environment and supply clean air in the absence of any major power disruptions.

Encouraging gradual change with these goals in mind is a much better position to take than preventing post catastrophe panic. As a psychiatrist who has been involved in disaster planning - having a real solution is always superior to meaningless reassurance. That would never work in one-to-one psychotherapy. Why would anyone expect it to work for agitated crowds?

George Dawson, MD, DFAPA




References:

1: Rosen J. Thinking the Unthinkable. Science. 2016 Jul 15;353(6296):232-7. doi: 10.1126/science.353.6296.232. PubMed PMID: 27418500.

2: United States Geological Survey (USGS). Yellowstone Volcano Observatory. Questions about supervolcanoes. Accessed August 2016.

3: United States Geological Survey (USGS). Fact Sheet 2005-3024. Steam Explosions, Earthquakes, and Volcanic Eruptions—What’s in Yellowstone’s Future? Accessed August 2016.

4: Cormac McCarthy. The Road. Vintage Books, New York, 2006. 287pp.

5: David Denkenberger and Joshua Pearce. Feeding Everybody No Matter What: Managing Food Security After Global Catastrophe, First Edition. Academic Press, 2014

Appendix 1: Estimated ash distribution from a Yellowstone supervolcano event.

From United States Geological Survey - Public Domain

Appendix 2:

I wrote a brief science fiction piece about psychiatric treatment after a supervolcano eruption in both original and annotated forms.

The Problem With EHR Software - A Clear Example

The above example is as clear as it gets in terms of illustrating the problem with electronic health record (EHR) software and associated hype and government mandates.  The idea that we need an EHR is a given, and I am not arguing that point.  I am arguing that the current software is inefficient, on par in many ways with software I was using on my PC in the 1990s, high maintenance, and a tremendous burden to any physician who has to use it.  It is also vastly overpriced with no end to that overpricing in sight - largely due to a monopoly of manufacturers and the use of a licensing model for the software.  And like practically every process in medicine these days, the implementation and actual use of EHRs is a highly politicized process that is far removed from the people who have to use it every day.

In the above example, I am tasked with a basic titration of gabapentin according to a recent research protocol (1).  All of the doses used are generic 300 mg capsules of gabapentin for the purpose of simplification.  The dose is titrated over 3 days to 300 mg TID (three times a day) or 600 mg TID.  People reading this may have picked up prescriptions with instructions typed out on the label about how to increase the dose to a therapeutic level.  In settings where a particular medication is used repeatedly and across a large patient population, the rate of titration and capsule side may need to be varied but the concept is the same.  

The question is how do I get this information to the pharmacy so that the medication can be dispensed to the patient in the most effective manner.  In the "old days" of paper records or the early hybrid models where  all of the orders and medications were entered into a text based computerized record, I would enter the orders onto a paper order sheet.  From there the pharmacist would either write up a parallel record for what the pharmacy needed to do or enter it into computerized pharmacy software.  An MAR (medication administration record) would be used by nursing staff to record the administration and time of administration of every medication.  There was a set of checks and balances because every dose of medication was checked at some point by a physician, a nurse, and a pharmacist.  In the 1980s and 1990s, clinical pharmacists would often have close relationships with the inpatient nursing and medical staff.  Those relationships were instrumental when it came to dosage changes, using novel medications, and making sure that all of the medication was given as scheduled.  The entire chain of events in the case of a low dose gabapentin prescription would start with a very simple handwritten order like the one below:

That is all written in my notoriously bad handwriting but I think it is perfectly legible.  I wrote it to show in two places that the capsules used here were all 300 mg and how they can be increased over three days.  More importantly, I turned on a stopwatch just as I started to write this order and it took me 1 minute and 50 seconds.

Compare a recent effort using an EHR.  The scratching in red at the top of this post is basically a worksheet on how to enter the medication without making a mistake.  The overall titration is the same (except the starting dose is 300 mg three times a day), but there are large differences.  In this case the physician is responsible for entering the medication into the pharmacy record and MAR at the same time.  The convenience with which that can be done is software dependent.  With the available software there are only two possibilities - add a new line of gabapentin doses to the HS, AM and Noon doses respectively over three days or rewrite the adjacent blocks of gabapentin doses and ultimately the 600 mg TID dose.  The difference is that the first procedure involved three steps and the second procedure four steps.  Each step also involves writing in the "Comments" section on each order to make sure that there is no confusion and that multiple doses of gabapentin do not end up being given over the course of the day.  For example in the red diagram for the single gabapentin 300 mg dose at the bottom of the column on the 28th I might enter:  "This is a single gabapentin 300 mg dose in the AM on 7/28/2016.  It is a one time dose".  Using any standard EHR will generate four or five separate orders for these simple titrations.  My first time through using the top method took me 30 minutes and at the end I had broken into a cold sweats.  I had to double check all of the text orders against my sketch (boxes and U-shaped checks) and the MAR.  I ended up calling the pharmacist and giving him a verbal version of my sketch as a back up.   The second method took me a total of 15 minutes.

This very basic example illustrates some huge problems with the EHR:

1.  Fewer people have hands on the medication orders - There may of may not be an immediate double check by the pharmacist.  Nursing staff are no longer entering the MAR and double checking how it looks.  The entire task and all of the associated time has been shifted to the physician.  When this happened, clinical pharmacists also disappeared from the floors.  The hype was that we have a newer and safer systems.  It should be apparent from my example that more can go wrong with the EHR titration than more traditional methods, even if there is a clinical pharmacist at the other end reading and approving hundreds of these order entries.

2.  More and more time is added to the physician - The EHR is a classic example of how numerous jobs including billing and coding, transcribing, and now data entry that used to be done by a pharmacist has been added to the physician's burden over the years.  It is as if physicians have unlimited time for all of these additional tasks.  The time constraint has to increase the likelihood of errors in the EHR.  If you have 5 or 10 minutes between patients and have to add even a mildly complicated order - it can easily take up twice that amount of time.  Administrators view this as a plus, because other jobs can be eliminated and physicians never get paid for administrative time.  By now it should be apparent that the enterprise wide EHR is such a financial burden on organizations that jobs need to be eliminated to pay for it - often many more jobs than the physician workload has assumed.

3.  The software itself has 20th century sophistication but without the report writing capabilities or data analysis - anyone who used spreadsheet or database software in the 1990s is used to the intensive data entry approach used in the modern EHR.  Should an extremely expensive, federally mandated piece of software be this clunky to use?  Should it take me 5-10 times as long to enter an order with this software as it did by writing it down on a piece of paper?  Should the final report of a hospitalization be a phone book sized incoherent document with very little information density?  I don't think that any of these constraints should apply.  I did not include the time it takes in direct conversations with a pharmacist to clarify what was entered in the EHR.  Every home computing environment these days is at least partially object/icon based to minimize typing where possible.  In the case of medication entry, the obvious solution would allow the physician to point and click medications on the MAR with no typing.  Select the medication and dose and enter it directly into the MAR with a few mouse clicks.  That would easily beat my time for writing it out and it would be more accurate than either of the approaches that I wrote about here.

I can only speculate about all of the business and political incentives in place that has resulted in the current EHR environment.  A lot of them have been clearly documented on the Health Care Renewal blog by searching EHR.   That search will also reveal a number of safety concerns and the inescapable political factors that currently exist in a healthcare environment that routinely ignores the concerns of physicians in favor of those with no medical expertise.    



George Dawson, MD, DFAPA      


Reference:

1:  Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Internal Med. Published online November 4, 2013. doi: 10.1001/jamainternmed.2013.11950.

2:  Brett Boese.  Mayo Clinic tries to avoid physician burnout.  Rochester Post-Bulletin.  July 29, 2016.  Link. 

Timely article on Mayo Clinic concerns about burnout and the EHR.  The Mayo Clinic is currently in the process of conversion to Epic EHR and will "go live" on various dates between the summer of 2017 and fall of 2018.  Tait Shanafelt was interviewed about a study he co-authored on the EHR showing the clerical burden led to decreased job satisfaction and burnout.  Responding to a number of strategies to reduce physicians clerical burden his conclusion was: "The specific strategy probably used likely matters less than recognizing that physicians should not be doing this and finding a practical way to have this task completed by support staff."

3:   Shanafelt TD, Dyrbye LN, Sinsky C, Hasan O, Satele D, Sloan J, West CP.  Relationship Between Clerical Burden and Characteristics of the Electronic Environment With Physician Burnout and Professional Satisfaction. Mayo Clin Proc. 2016 Jul;91(7):836-48. doi: 10.1016/j.mayocp.2016.05.007. Epub 2016 Jun 27. PubMed PMID: 27313121.

4:  Shanafelt TD, Hasan O, Dyrbye LN, Sinsky C, Satele D, Sloan J, West CP.Changes in Burnout and Satisfaction With Work-Life Balance in Physicians and the General US Working Population Between 2011 and 2014. Mayo Clin Proc. 2015 Dec;90(12):1600-13. doi: 10.1016/j.mayocp.2015.08.023. Erratum in: Mayo Clin Proc. 2016 Feb;91(2):276. PubMed PMID: 26653297.

The Burnout Disease

I got an ominous e-mail from the Psychiatric Times yesterday.  The title was "Before it's too late".  It reminded me that at some point the professional trades are just like everybody else - desperately vying for attention through provocative headlines.  The irony is that that there are numerous areas in medicine and psychiatry that could be labeled in this manner but are routinely ignored.  I recently point out that detoxification services and the shortage of psychiatrists have been ignored for 30 years.   It may be accurate to say there was a lot of lip service paid to the psychiatrist shortage with no real action.  At any rate I decided to click on the provocative e-mail to see what the new risk was and was taken to a set of 6 slides on burnout or more accurately "6 Strategies To Prevent Physician Burnout." by Eva Szigethy, MD, PhD.

The presentation begins with a definition of burnout as chronic exhaustion and decreased interest in work.   Three stages were defined with more mild and transient symptoms in Stage 1 progressing to Stage 3 with chronic symptoms that progress to psychiatric and physical disorders.  That basic definition contains a lot of information and assumptions.  The basic assumption is that a person must be interested in work.  I have certainly encountered people who were interested in work, but they are generally few and far between.  If I had to globally characterize them, they tend to be people who bring a lot of creativity and skill to a particular job and for various reasons they are allowed to use that creativity and skill in an optimal way.  I don't think that those characteristics map onto any particular degree or occupation.  I think it is probably the driving force behind why people want to work for themselves or establish their own businesses.  There is no better way to maintain a high level of interest in work than to be working for yourself.   The introduction of any management hierarchy is a potential threat to interest in work.

There are also a large number of jobs (if not most jobs) where people work very hard and are not rewarded.  Oren Nimni wrote an interesting article about this in Current Affairs while commenting on the recent plagiarism concern about a political speech.  He points out that the American economy is fundamentally skewed and unfair and political speeches about values, hard work and achievement based on merit do not necessarily apply.  He is blunt about telling people that hard work will necessarily get them somewhere is a cruel lie (par 10).  Many of the jobs he is referring to here are physically exhausting and as a physician, I can say with certainty have a high probability of injury and disability.  It is difficult if not impossible to work at many of these jobs until you are old enough to retire.  The path I observe is that when you are too disabled to do one of these jobs, you move onto to a more sedentary and even lower paying job.  This may be an entire group of workers for whom the idea of burnout is a luxury.  Every day is exhausting whether you have physically adapted to the circumstances of the job or not.  When I think about these definitions of burnout, they necessarily don't apply to a lot of occupations.

The Psychiatric Times slides go on to identify the early markers in the burnout process and what can be done to prevent them.  They start out with an assessment of the weekly schedule and eliminating nonessential tasks.  There is the implicit assumption that the potential burnout casualty is in control of the schedule.  I can say with certainty that every person who I have ever seen who was anxious or depressed as a direct result of their work environment - this is never true.  In fact, the people in control of the schedules tend to be some of the most unpleasant people.  They work from a general concept that work is standardized, everyone needs to do it the same way, and if workers don't like it - they can always find another job.  Those work environments are partitioned into highly reimbursed professionals who have to tolerate out of control managers and non-professionals who have to put up with similar management.  The professionals may have slightly more leverage in the workplace.   In the case of physicians, they used to have leverage because of legal requirements in many healthcare settings.  Managers have found their way around these requirements and in practically all organizations there is a chain of command that involves physicians being ordered around by nonphysicians with no medical expertise.  What constitutes management expertise is anybody's guess.

The suggested strategy to assess various professional goals and the impact of the work on the physician is the next step.  In an ideal world there would be some freedom to move laterally within organizations or between roles.  In the regimented world of physician employees and managed care organizations it is next to impossible.  One of the biggest burnout factors for physicians is the measurement of so-called productivity.  Productivity expectations in most organizations are a setup for overwork and overinvolvement in the most mindless aspects of medical practice - billing and coding and the electronic health record (EHR).   There is no room for breaks, sleep, or intellectually stimulating activity.  The entire process is driven by management and the final product (in spite of all the hype) is an inferior one.  I have written on several occasions about how the most elaborate and expensive EHR - costing millions per year in licensing fees cannot seem to produce a coherent report that I could print from a hundred dollar software package in the 1990s.  And that doesn't take into account that every physician in America is now a scribe in this process - producing terabytes per day of useless data - used only for billing and coding purposes.

The human factor in burnout especially for physicians is always a huge question mark.   Who can you turn to?  One of the colleagues in your system who in all probability is as burned out as you?  A colleague outside of your system who has successfully evaded corporate medicine and is quite happy to advise you on how to do the same?  Most physicians in this situation feel trapped either way.  Many have been able to escape medicine completely, either working for less or in medical industries.  In advising colleagues over the years, jobs within the industry are far more difficult to get - almost impossible if you are middle aged and have been focused on nothing but productivity for decades.  Often the best outcome is to settle for less and retire, especially if there are signs that mental and physical health are being affected.  Under duress many physicians add to the problem.  They get involved in management specifically utilization review or similar rationing jobs for managed care companies.  I have also encountered physicians who view themselves as being disruptive and who tell me that I need to learn how to "play in the sandbox" with the other health care managers.  They teach physicians management as though anything but managed care rationing strategies are likely to apply.  That may be a temporary solution for that particular individual.  At a personal level, I would not be able to suspend my knowledge of medicine and psychiatry to make arbitrary cash decisions for my employer.  But clearly that is just me.  Plenty of physicians have gone that route.

The final consideration of vacations is also not a good solution.  Although it has not been studied, I can predict that any physician with a serious burnout problem will feel almost as bad on the first day back from vacation as the day they left.  By day 2 they certainly will feel as bad.  Many work environments for physicians these days are hostile territory.  The goal is really to get in and get out with as minimal damage as possible.  Many will leave as early as they can and if they have remote EHR access - work from home into the night.  I have called primary care clinics at  7PM and talked to a physician amid a flurry of typing sounds and mouse clicks from their colleagues in the background.  There is no way that you can walk into that environment and not feel burned out.

My conclusion about burnout is basically unchanged from an earlier post.  If the Psychiatric Times, had invited me to made a slide set (that won't happen anytime soon) - it would have been just one slide:

               


George Dawson, MD, DFAPA


References:  

1:  Eva Szigethy.  6 Strategies to Prevent Physician Burnout.  Psychiatric Times.  July 22, 2016.

2:  Oren Nimni.  Melania's plagiarism actually just shows how vapid political speeches are.  Current Affairs.  July 19, 2016.

3:  My previous posts on Burnout.

       

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