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Friday, October 17, 2014

Being Honest Won't Save You - Lessons In Medical vs. Business Accountability






Every now and again I flash back to a surgical rotation that I was doing at an old county hospital.  It was quite run down.  We had a large surgical service comprised mostly of people with gunshot wounds, cancer patients, and people who were in long term care hospitals for mental illness who developed acute surgical problems.  Most of the patients who had gunshot wounds had been shot by the police and they had police officers posted outside of their doors.  On some days it seemed like there were a lot of police officers outside of every other door for quite a distance down the hallway. We did two sets of rounds - in the morning after the surgical procedures and another set of rounds at about 6 or 7 PM.  The evening rounds always ended under fluorescent lights in what is probably a long abandoned nurses station.  In this particular case we are rounding with a senior surgeon and a junior surgeon.  The senior surgeon has just demonstrated how much he knew and how little the residents knew about the effects and importance of gastrointestinal tract hormones.  After a few moments of uneasy dead air, the junior staff asks the intern: "What was Mr. X's calcium level this afternoon?"  The labs were typically run at 4PM and in those days we would have started to see results at about 5 or 5:30, but we were all rounding at that time and attempting to answer questions about GI hormones.  The conversations went something like this:

Staff MD:  "What was Mr. X's calcium level this afternoon?"
Intern:  "I don't know."
Staff MD:  "What?  I expect you to run this service.  How can you run this service if you don't know what Mr. X's calcium level is?"

The team got quite nervous in situations like that.  Training in medicine puts you directly in the line of fire or at least it used to.  These days commentary and affect like I witnessed that day might lead to some type of disciplinary procedure for the staff physician.  Something that could be passed down on credentialing forms and haunt a physician for the rest of his or her career.  A type of pseudoaccountability arranged by the bean counters essentially to manipulate physicians.  In this case, it was considered to be a learning experience and culturally appropriate.

In this case the intern in question seemed to recover.  Things went well for another few days.  And then he was gone.  The rumor was he was asked about another lab value, gave an answer that was slightly incorrect as in no physiological difference between the answers. He was fired for making up the answer.  Keep in mind that this incident occurred at a time when there were hundreds of lab values to track and the technology was at a primitive state relative to what is currently available.  The computers were slow and getting results took a lot longer.  Medical students, interns and residents had to write the labs down on cards using whatever shorthand they could devise.  In the process some data was memorized but not all or most of it.  But the difference here is that the integrity of the answer was called into question.  The assumption was that you either know the answer for sure  or you say you don't know.  There are no near misses.  The judgment is that you made something up and that is unacceptable.  In the years since, I have seen quite a few colleagues fall by the wayside as a result of similar incidents or what were considered to be errors in judgment by the senior faculty.

In recent times, I think there is a tendency to lump this behavior in the category of senior faculty being abusive toward physicians in training.  That certainly may be true, but it is also true that it draws a very clear line about what you need to be doing as a physician as opposed to what you may have done in your undergraduate major.  You can no longer make things up like you used to do in your philosophy and English literature classes.  You have to be brutally honest about what you know and what you don't know.  I don't think there is a physician alive who will not tell you that knowing this is one of the most critical aspects of training as a physician.  The ultimate test of whether you are patient centered is whether you will not try to protect yourself - but whether you can be brutally honest even in a situation that may put you at risk professionally.  Can you acknowledge mistakes, lapses in judgment and most importantly a lack of knowledge or expertise?  Patient safety depends on it.  That atmosphere also has the effect that you show up for work.  If you know that you are a target for any faculty who want to criticize you, you tend to want to know everything there is to know about the patients on your service.  In contrast to the events where the question does not get answered I have seen residents give tutorials on ventilator settings or pressure recordings by Swan-Ganz catheters.  They were motivated to some degree by knowing that teaching staff would be asking and their assessment depended on their answers.  

The reason for that introduction is that it frames the backdrop for a discussion from a financial thread with a very interesting title: Will Ebola Vanquish the MBAs Who Run Our Hospitals?  It is a title by a blogger and certainly eye-catching.  I have followed this blogger for a number of years and agree with a lot of what she has to say about the way financial services are managed in this country.  I have disagreed with her about some of her medical opinions, but this post is something that I can agree with.  I was recently e-mailed about my tendency to selectively find research that supports my opinions.  I consider this to be more opinion to support my opinion.  Research on how businesses manage medicine is as scant as research on management in general.  Business people tend to produce papers suggesting there are deficiencies and then say how they will correct those deficiencies.  There is really hardly any research to support business opinion.  The opinion in this case looks at a topic I frequently comment on - how can business people with no medical or scientific training manage physicians and medical facilities?  In my opinion they clearly can't but let's look at what is presented in this article.

The basis for the article is essentially opinion in the press and the opinion of a medical blogger.  The conflict-of-interest here that is usually glossed over is that any journalist, newspaper, or blogger wants the public reading their stuff.  It will be provocative or sensational.  A measured analysis is not typically seen.  For example the comparison of staff infection rates between the staff at Dallas Presbyterian Hospital (DPH) and Doctors Without Borders (DWB) in Liberia seems pointed, but the obvious question is whether the infections rates vary with experience.  For example did the DWB staff in the earliest stages of their involvement have infection rates as high as were portrayed in the DPH staff.  Can a direct comparison be done without that information?  The highlighted emergency department (ED) problems are similarly problematic.  If you pull up the Internet sites for the DPH system of care they are affiliated with a number of inpatient psychiatric units.  Is the wait time a reflection of a large pool of chronically mentally ill or poorly stabilised psychiatric patients being stuck in the ED?  If that is true it would still be consistent with some of the authors concern about the lack of public health concern and the fact that lower socioeconomic classes come face to face with the wealthy in such settings.  It is also an aspect of the mismanagement by rationing that is pervasive with systems of care managed by large businesses.

I have first hand experience with infection prevention in hospitals and attempt to stop widespread outbreaks from respiratory viruses.  Keep in mind that the Ebola virus is not an airborne virus.  All of the remarks in this paragraph are about airborne viruses especially Influenza virus.    For a number of years I was extremely disatissfied with the epidemics of respiratory viruses that swept through the staff where I was working.  Employer rules about paid time off only worsen the situation because the incentive is to work when you are sick to prevent loss of vacation days.  But the most frustrating part of the problem (apart from being sick 3-5 times a year) was that the employer had no real interest in doing anything that might reduce the risk of infections.  The intervention I suggested was just improving air flow in certain buildings.  The standard reply that you get is "wash your hands and cough into your sleeve."  Those are certainly common sense measures but as far as I could tell had no impact on the rate or severity of infections each year.  Hospital administrators everywhere seem to be in denial of the fact that airborne pathogens exist and washing your hands and coughing into your sleeve will not protect you against airborne pathogens.  I was also a member of two different Avian Influenza task forces.  At the time there was much uncertainty about a widespread epidemic that could not be contained.  We were setting up for the worst case scenario of thousands of people (both infected and not infected) coming into EDs and how to triage and treat people.  After years on these task forces it became apparent to me that nobody was really interested in planning for the prevention of mass casualties from an airborne virus.  There was no planning for any additional negative pressure airborne isolation rooms and no planning for any additional bed capacity in the event of a widespread epidemic.  There was planning for what to do with the expected bodies.  In the end it seemed that all of our hopes were pinned on a rapidly disseminated vaccine or antiviral medication.  The specifics of the antiviral medication were murky.  We were shown a picture of a large pallet of oseltamivir sitting in a warehouse somewhere.  From a business administrator's standpoint, planning to use imaginary resources from the government is always preferable to more functional planning because it is free.  My personal experience in this area from volunteer work on respiratory viruses is entirely consistent with the notion that health care businesses are not administered in a way that is consistent with public health needs in the case of infectious epidemics.

The Naked Capitalism article contains analysis from Roy Poses, MD of the Health Care Renewal Blog.  He looks at inconsistencies in the media and concludes that this is another case of health care leaders being untrustworthy.  That appears to be a central theme of his blog and he goes on to criticize them for being inconsistent, suppressing information from employees that may be critical to public health, and having an inflated sense of self importance.  These patterns are easily observed by physician employees of health care organizations.  For at least a decade after passage of The Health Insurance Portability and Accountability Act of 1996 (HIPAA) it was impossible to get necessary information from health care organizations, even in the case of needing to provide emergency care.  I would routinely request information and even send a HIPAA compliant release signed by the patient and I would get a blank form the other hospital saying that my patient had to sign their form and fax it back.  Hospital administrators were a big part of that process.  It is common for the clinical staff to be buffeted by the next big idea from their administrator.  That can range everywhere from high school style pep rallies that are supposed to improve employee morale to a new productivity system that is guaranteed to get even more work from physicians.  In every case, the administrator in charge could be making 2-5 times what the average physician makes for considerable less accountability, practically no "evidence based" methodologies, and no measurable productivity.  As pointed out in the article, public relations is much more of a factor in the CEO's reputation.  From the article:

" On Health Care Renewal we have been connecting the dots among severe problems with cost, quality and access on one hand, and huge problems with concentration and abuse of power, enabled by leadership of health care organizations that is ill-informed, incompetent, unsympathetic or hostile to health care professionals’ values, self-interested, conflicted, dishonest, or even corrupt and governance that fails to foster transparency, accountability, ethics and honesty." 

There are additional lessons from the decimation of mental health care in the United States, especially care delivered at tertiary care and community hospitals.  There is perhaps no better example of low to no value service that is the direct result of non-medical management.  There is no coordinated public health effort either improve the care of psychiatric disorders or specific high risk behaviors like suicide or homicide.  The standard approach is rationing of both care that would result in stabilization but also bed capacity that would alleviate congestion in emergency departments.  There should be no debate on cost, inpatient psychiatric care is without a doubt the low cost leader and is set to match reimbursement from a high turnover low quality model.  Psychiatric services in clinics and hospitals have a lot in common with what Dr. Poses observes on the administrative side of many health care organizations.

Responding to the question of  "Will Ebola Vanquish the MBAs Who Run Our Hospitals?" - my answer would be no.  It is always amazing to consider how so many people in business with so little talent can end up running things and making all of the money essentially through public relations, advertising and lobbying politicians.  There is no shortage of self proclaimed administrator-visionaries.  The author here should know that their power is consolidated around the same strategies that have worked for the financial services industry.  Managed care business strategies based on no science or input from physicians are now in the statutes of many states and in federal law.  They have successfully institutionalized business strategies designed to return profits to corporations as the rules that govern healthcare.  The pro-health care business lobby essentially gets what they want and the professional organizations are weak and ineffective, but continue to browbeat their members for contributions.  Administrators have a lock on running health care and demanding whatever accountability they demand from health care professionals while having no similar standards for themselves.

I can't think of a worse scenario for addressing potential public health problems whether that is an infectious epidemic or the continued mental health debacle.



George Dawson, MD, DFAPA

Supplementary 1:  Kaiser Family Foundation brief PowerPoint and Infographic on the current Ebola out break.

Supplementary 2:  I decided to add the above table comparing the accountability of physicians with business administrators.  Certainly there may be some things I have missed on the business administrator accountability so if I missed anything please let me know and I will include it.  From what I have observed, health organization and hospital CEOs are typically accountable to a Board of Directors that has very little physician or medical representation.  Often the Board is stacked with people who rubber stamp what the CEO wants to do.  Like the web site referred to in the above post there is often an aura that the CEO and the Board have visionary-like qualities that are based on public relations and advertising rather than any academic work or actual results.  I have never really seen an administrator who was a visionary or knew much about medicine - but  you can certainly read their proclamations about how medicine should be reformed on a daily basis in many places on the Internet.  The usual argument for all of the physician accountability is that it is a privilege to practice medicine and therefore regulation of physicians needs to reduce the privacy rights of physicians and subject them to much closer regulation than other professionals.  Why wouldn't that approach apply to the people who actually determine whether a patient gets health care, medications or a specific benefit?  Why wouldn't that same logic apply to the people who really run the health care system?
  

Friday, February 7, 2014

Medical Knowledge Goes A Long Way - Or Does it?

"Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality." - Frontiers in Microbiology October 1, 2013.

For starters this is a lengthy and somewhat obsessive look at a personal episode of illness and the implications it has for some of the common threads on this blog ( overidealization of general medicine, dislike of psychiatry, inaccurate comparisons of psychiatry to the rest of medicine, wild criticism of psychiatry, etc.).  So if you are not into that - this would be a good place to stop and move on...........

I have been off work 9 out of the past 10 days with an upper respiratory infection leading to an exacerbation of asthma.  At least that is one theory.  I first noticed it when I stepped off my ergometer trainer about 2 weeks ago and noticed that I did not seem to be able to take a deep breath and I was wheezing mildly.  I saw an Internist the next day who did a history and examination and got a chest x-ray and an electrocardiogram - both of which were normal.  She decided to double the dose of a corticosteroid inhaler that I was using and told me to increase double the dose of the albuterol inhaler I was using.  She said she would not add oral prednisone at this point.  When I got home I realized that my corticosteroid inhaler was empty and I needed a new one.  The office was contacted and sent a prescription for the previous dose rather than the new dose.  When I called and asked them to read the documentation, the note mentioned an even higher dose that was not possible with the inhaler I was using.  The inhaler cost $187 for one month so I figured it was easier just to start using it rather than wait for them to sort of all of the communication problems, especially because the physician was not available for another several days and I was still wheezing.

Two days passed and my breathing seemed slightly better so I went into work.  By mid afternoon the inability to take in a deep breath came back and I went to an Urgent Care clinic through my health plan right after work.   The new doctor repeated the history, physical, and chest x-ray (again negative).  He prescribed a more intensive course of therapy with a 12 day prednisone taper starting at 60 mg/day and a nebulizer machine with ampules of 2.5 mg albuterol.  He told me to keep taking both inhalers and add both of these.  When I got home I took the prednisone and assembled and used the nebulizer.

I will digress to say that I am a firm believer in the absolute need to control blood pressure and pulse.  I measure my blood pressure and pulse four times a day or more depending on the circumstances.  White coat hypertension probably happens but how many people know what their blood pressure is once they get back home?  I know from personal experience that a hostile work environment can drive both your pulse and blood pressure through the roof not just for days but for weeks to months.  The only time I am comfortable being hypertensive is when I am exercising because it it physiological, I have been monitored doing it by sports physiologists and they were happy with it, and I know there is a compensatory post exercise response that controls BP and pulse in the long run.  I take what most physicians agree is a homeopathic amount of antihypertensive but my BP is never greater than the CDC recommended cut off blood pressure of 120/80.  It is usually 10 points less.   That belief comes from seeing many people over the years who had decades of untreated hypertension that either they or their physician seemed to attribute to something else.  Psychiatrists are occasionally in the situation of treating patients with extremely high  blood pressures like greater than 200 systolic and 120 diastolic who refuse treatment.  They are usually being seen by psychiatrists because of the need to get a court order for them to be treated and that often takes several weeks, putting the patient at risk all the while.  I have seen the full spectrum of blood pressure related problems and there is only one logical conclusion that blood pressure needs to be well controlled.

I am also a student of respiratory viruses and a veteran of two different avian influenza task forces.  The task force experience left me quite pessimistic about our ability to fight off any actual pandemic for a reason that is quite striking - the denial that there is an airborne route of infection.  Everyone on the task force was focused on hand washing and controlling fomites and there was very little focus on what was needed to contain airborne infections, probably because we learned that capacity would be overwhelmed on the first day of the pandemic.  At that point we are basically in a slightly better position than we were in the influenza epidemic of 1918.  At one point they showed us a couple of plastic covered pallets of Tamiflu in a government warehouse somewhere.  I stopped attending when they started to talk about where the dead bodies would be stored.

But my interest is also in the area of common everyday respiratory viruses.  When you are working in a hospital with 1970s era ventilation systems (contain the air to save heat) you witness the staff around you and yourself and the patients get ill in mini-epidemics 3 - 4 times a year.  All with the same symptoms of varying severity.  Some will end up on antibiotics and some will end up on Medrol dose packs or both.  It happens whether you wash your hands or not.  At some point I started to e-mail the Minnesota Department of Health and inquire about the respiratory surveillance of flu and flu like illness.  At some point they got tired of my email and put it all online.  The bottom panels show (with a lag time) the likely viral culprits based on various identification methods.  Rhinovirus and adenovirus are among the usual suspects.  Reading my copy of Gorbach, Bartlett and Blacklow confirms the syndromes.These are the kinds of trends I would see every year.  I consulted with a top expert in airborne viruses in building.  He had done the first studies to confirm that viruses can be sampled in the airflow of buildings and that they are typically airborne viruses.  For two years, I studied the airflow and filtering characteristics of buildings and how older ventilation systems might be modifiable to reduce the risk of respiratory infect by airborne viruses.  I looked at the specific air flow characteristics of the building I worked in.  I surveyed the employees on each unit showing a high clustering of upper respiratory infections and and flu like illnesses.   During that entire time I got numerous respiratory infections with no exacerbations of asthma, but according to the following graphic - it was just a matter of time (click to enlarge):

            

After the initial nebulizer treatment my systolic and diastolic blood pressure was up about 30% and I was feeling somewhat agitated and anxious.  I had only had one nebulizer treatment in my life and it was about 20 years ago.  I looked at the doses and found the inhaler contained 180 mcg of albuterol compared to the 2.5 mg in the nebulizer with greater bioavailability.  In other words the nebulizer delivered 14 times the dose and I was told to use it up to 6 times a day.  I slept about 2 hours that night.

The next day I ran a drug interaction search on my revised list of medications and several potential drug interactions were noted - a couple of them significant.  I logged into my health plan and sent my personal Internist a note with several question on the interactions with drugs and my existing medical morbidities.  He called me up concerned that I might have the flu, but I had just seen him and been referred for an extensive immunology evaluation for the flu shot and got it.  I told him about my experience with the nebulizer and he chuckled:  "In the ER they might give you this very 1 - 2 hours but of course you are hooked up to a monitor and they are checking your blood every hour."  At this point I have not had a single blood test.  He suggested that I try a new inhaler - levalbuterol and the equivalent nebulizers.  They were supposed to have fewer side effects.  I spaced the treatments out exactly 8 hours and five minutes after the third treatment my heart rate shot up to 140 beats per minute and a blood pressure of 147/103.  I took some medication that I knew would bring it down in about 45 minutes, but also prepared to call 911 if it continued to climb.  Gradually over the course of 30 minutes my blood pressure and pulse recovered.

So what can be concluded by my latest foray into the healthcare system?

1.  Medical knowledge may not lead to any improvements.  As far as I can tell nobody is very receptive to the idea that respiratory viruses exist and that while hand washing is helpful it will not necessarily protect you against some of the worst viruses.  The unreceptive parties occur at all administrative levels and seem content with watching employees get recurrent viral infections and use their paid time off.  Is that a form of cost shifting?

2.  Syndromal diagnoses are alive and well in medicine and not just psychiatry.  I have talked with 4 physicians during this week long bout of illness and none of them have a clear diagnosis other than an exacerbation of asthma.  The asthma we are talking about is not a specific type or subtype that may have implications for treatment - but the good old heterogeneous type.  As heterogeneous as just about every known psychiatric diagnosis.  The first physician thought the likely cause was dry winter air.  By the time I had seen the second physician I had some additional symptoms to suggest a URI.  Only my personal physician seemed concerned that I may have influenza and called me back a second day to make sure that I had not developed a fever.  I had vital signs determined, peak flow meters, oxygen saturations, 2 chest x-rays and an electrocardiogram.  None of the tests was a biological test for asthma or whether there was an underlying infectious agent.  None of the tests were positive or could quantitate my illness.  Recall that a typical argument rolled out about psychiatric diagnoses is that there is no specific test and that they are all syndromes.  I learned that clinics in my health care system no longer do the rapid test for influenza because it is not considered to be accurate.  In all cases I was being treated based on a syndrome and nothing else.

3.  Could a more specific diagnosis be worthwhile?  Most certainly since there is some evidence that rhinovirus is a common cause of asthma exacerbations and may also be a cause for asthma in childhood.  There is also evidence that rhinovirus can replicate its RNA in the lower respiratory tract for up to 16 days post infection.  It was only recently discovered that rhinovirus inhabits the lower respiratory tract and can replicate there.  The biological test that was done for influenza is no longer used because it was inaccurate, would that be useful to know?  I have a previous post here about asthma endophenotypes.  Is there an endophenotype for rhinovirus induced asthma?  Is it caused by epigenetic mechanisms?  These are all parallel questions that psychiatric researchers are working on right now with most major psychiatric disorders.

4.  Cost shifting to the patient is paramount from several sources.  I purchased 3 - $200 inhalers in 3 days that were not covered by my insurer.  The first one was an error because it would have covered 2 weeks of treatment and it did not match the documentation in the original note.  In all three cases the pharmacists warned me about the high cost of the inhaler, but when I asked them if there was a generic substitution they said there was none.  The current albuterol inhaler also has no generic apparently because it is the only environmentally friendly one.  That is the difference between a $50 copay and a $4 copay.  There is also an angle from the perspective of ethical purism and pharmaceutical manufacturers.  Is this a case to be made for samples?  Should a patient try a sample of the inhaler in their doctor's office to make  sure they can tolerate it and know the price before going to the pharmacy?  That way there would be an assurance that the patient could tolerate and afford a very expensive medication.  I currently have $400 of inhalers that will be used twice and are otherwise worthless to me.  The other scenario that is difficult to contemplate is a person being forced to drive away from the pharmacy without a medication due to the surprise cost or copay.

5.  There was minimal discussion of side effects and contingencies but scripting was noted.  Scripting is a public relations initiative where health care personnel are trained to ask questions that the patient may be asked about in a satisfaction survey.  For example at the end of the visit the physician says: "Do you have any additional questions for me today?"  A week later you get a survey to rate the physician on whether or not he asked that question.  In the meantime no warnings about prednisone or what to do if I got hypertension or tachycardia from the albuterol.  I was told that I might expect some palpitations and that might be expected because "there was more medicine in there than from the inhaler".  The levoalbuterol was supposed to solve the problem but it resulted in significant tachycardia and I later learned it was pulled from a hospital formulary because it did not "work as advertised".  That is the optical isomer did not protect against side effects like tachycardia.

6.  Pattern matching is implicit and probably carries the day.  I have previously written about the importance of pattern matching in medical diagnosis and it was probably a significant factor in all of my physician encounters.  They looked at me and could tell I was not acutely ill - I did not need to go to a hospital.  There are various ways of phrasing it but that conclusion was uniform.  The pattern matching also probably drives a lot of the questions that flowed from the patterns of asthma exacerbation in their previous patient encounters.

7.  Complex medical diagnoses are a process.  On this blog I have pointed out why a checklist screening is generally an inadequate approach.  There is probably no better example than logging in to your health care system's triage software and realizing that your problem is not listed among the choices.  In this case information changed over time from asthma due cold air to asthma due to a viral exacerbation.  The treatment was also significantly and expensively changed along the way.

8.  Asthma and related conditions are a huge public health problem.  The prevalence of asthma is about 10% in developing countries and it accounts for 1 of every 250 deaths worldwide.  Only 1 in 7 people with asthma have it well controlled.  Public health interventions seem like a last resort.  Trying to get people interested in the true nature of airborne viruses and how to prevent these cyclical infections is practically impossible as far as I can tell.  I have corresponded with the head of the Cochrane Collaboration section on Physical interventions to interrupt or reduce the spread of respiratory viruses who cautioned me that no one knows how URIs spread or how many of the interventions work!  Even World Health Organization (WHO) initiatives seems to leave out the all important aspect of building design and airflow.  There seems to be a distinct medical bias when it comes to respiratory infections.  The only potentially useful and very cost effective public health interventions that I may have availed myself of are the pneumococcal vaccine polyvalent (Pneumovax) vaccine and the influenza vaccine.

A related issue is how much epigenetics comes into play, specifically epigenetic modifications that occur to environmental exposure of let's say - rhinovirus.  Is it possible that exposure to rhinovirus causes more long term health problems for kids than exposure to cigarette smoke?  If that is even possible, why aren't we doing more about it?

9. The elegant hypothetical molecular mechanisms of disease don't translate well to clinical medicine in the case of asthma any more than they do with mental illnesses.  Skeptics and critics of psychiatry (most of whom seem to know nothing about molecular biology) frequently use this rhetoric without understanding how little these mechanisms apply in other major diseases.  Cytokine signalling alone has been described as "having such staggering complexity that the long term behavior of system is essentially unpredictable."  Brain complexity is far greater.  The use of prednisone to shut down inflammation is more of a shotgun approach to shutting down inflammation rather than anything to do with disease specificity.  Given the fact that endophenotypes are not actually diagnosed at this point and viral infections often are associated with acute onset of asthma, it would seem that there is not a lot of diagnostic specificity beside the syndromes.  There is also the question of the time course of improvement.  People have ideas about how quickly medication prescribed by a psychiatrist should take to work.  Very few of those ideas are accurate.  On the other hand here I am on day 16 of treatment for asthma and I am still ill.  Aren't real treatments that are based on elegant biological mechanisms supposed to work faster than that?

In the end I am reminded that psychiatry is no different than the rest of medicine that deals with complex heterogenous conditions.  Diagnoses are imprecise, there is a focus on patterns, there are very few pathognomonic or gold standard tests, and the management of side effects of medications is as important as treating the underlying problem - at least in non acute situations.  Information transfer between the patient and physician is imperfect and nobody seems to be working on ways to optimize it.  If anything the critical time domain is being restricted by businesses and governments.  Those same businesses and governments seem completely disinterested in non medical approaches to reducing disease burden like building design.  There are plenty of false positives and the best assurance you can get is from a single physician who knows you the best.  Despite all of the medical care I have received these past two weeks, I think about all of the decisions I had to make on my own and ask myself: "How do people with no medical training decide what to do in this situation and how do they know what information is relevant?"

It must be mind boggling.

Despite all of the technology and medical knowledge a lot of the information transfer still comes down to what happens between the patient and the doctor.  There has to be enough time for that  to happen.  It has to be meaningful and the patient should know what to do if problems occur.

That is true for doctors of all specialties.

George Dawson, MD, DFAPA

Supplementary Information 1:  The supplementary material here is a graphical primer on allergic asthma and how exacerbations of asthma may occur.  Rather than an airborne allergen a respiratory virus triggers the cascade of events that leads to the flare up (top figure).  That fact is still only recently being elucidated.  For example, rhinovirus is a common initiator and it has only recently been demonstrated that rhinovirus replicates in the lower respiratory tract and that rhinovirus RNA can be present for as long as 16 days.  As indicated by the tables that follow, cytokine signalling in asthma is complex.  The authors show here it may involve up to 22 separate cytokines.  Corticosteroids like prednisone and prednisolone inhibit gene expression via transcription factor NFκB to decrease the activity of cytokines.  They also reduce the activity of nitric oxide, prostaglandins, leukotrienes, and adhesion molecules by similar effects on on synthesis and decrease lymphocyte activity.

























Supplementary Information 2:  I have a post available that looks at the early addition of prednisone, but there is a lot of additional information.  The following table is the actual course of treatment that I received from four different physicians (color coded) over the course of two weeks.  It is posted here for discussion purposes only and should not in any way be construed as medical advice.  The disclaimer for this blog applies in that nothing here is for the purpose of medical treatment or advice.



Monday, August 5, 2013

Asthma Endophenotypes? Their Implications for Psychiatry

Asthma is an annoying and sometimes fatal disease.  I have first hand experience with it because I have had asthma for at least 40 years.  Like many of my personal medical afflictions that I have posted about on this blog it was initially missed and not treated.  According to recent studies, that is still a common experience.  When I was a teenager, wheezing when mowing the lawn was apparently considered a normal reaction.  When I developed a more systemic reaction right in a physician's office, my parents were taken into an adjacent room and advised that it was apparently all "in my head" and it was some sort of psychosomatic reaction.  The psychosomatic reaction responded well to epinephrine injections and diphenhydramine.  Even when I was in medical school the treatment of asthma was shaky.  I was taking theophylline pills twice a day for several years and the patients I began treating for exacerbations of chronic obstructive pulmonary disease were all on aminophylline drips and corticosteroids.  We all had to memorize those protocols and of course know the mechanism of action (now invalidated) that was based on Sutherland's Nobel Prize winning work on cyclic AMP.  Today theophylline is considered a tertiary option for uncontrolled asthma rather than a first line treatment.

 As a fourth year medical student, I presented a very well received seminar on "slow reacting substance of anaphylaxis" or SRS-A now known to be a mixture of leukotrienes.  Eventually the treatment of asthma changed and glucocorticoid inhalers became the treatment of choice for a while.  As any primary care physician or asthmatic patient knows - no two asthmatic patients are the same.  As an example, peak flow meters are routinely used to measure asthmatic control.  No matter how badly I am wheezing, I can always max out that peak flow meter.  Asthma is a complex disease with varied presentations and the current treatment algorithms are complex with varied medications.

The diagnostic criteria of asthma seem relatively straightforward and are listed in the table below:

Diagnosis of Asthma (see additional details in National Heart, Lung and Blood Institute reference) and reference 8 below:
1.  Recurrent symptoms of airflow obstruction or airway hyperresponsiveness (eg. wheezing, chest tightness, cough, shortness of breath.)

2.  Objective assessment as evidenced by:

     A.   Airflow obstruction as least partially reversible by inhaled short acting beta2 agonists as demonstrated by any of the following:

-        Increase in FEV1 of ≥ 12% from baseline
-        Increase in predicted FEV1 of ≥ 10% from baseline
-        Increase in PEF (liters/minute) of ≥ 20% from baseline
            
     B.   Diurnal variation in PEF of more than 10%
     C.   No other causes of obstruction
FEV1 = forced expiratory volume in 1 second (liters)
PEF = peak expiratory flow

Medicine texts have traditionally used breakpoints in the above parameters to distinguish mild, moderate and severe asthma.  Despite what seem to be clear diagnostic criteria a recent review (8) in the New England Journal of Medicine states:  "Most patients with asthma have mild persistent disease which tends to be underdiagnosed, undertreated, and inadequately controlled."  The reference cited in that review points out that only 1 in 7 patients achieved good control of their asthma.  

There has been a sudden surge in research on asthma phenotypes, endotypes, and endophenotypes.  Endophenotypes are subtypes of a particular phenotype that are thought to have a common pathophysiological mechanism or in the case of psychiatry a biochemical, neurophysiological, neuropsychological maker that allows for the subclassification.  If you have attended any serious psychiatric genetics course in the past decade you have probably heard about endophenotypes.  Gottesman and Gould published a widely cited paper in the American Journal of Psychiatry in 2003 discussed the concept and its application in psychiatry.  There have been 132 references to papers on endophenotype in the Schizophrenia Bulletin alone, including a special theme issue.

A group of 5 asthma endotypes have been suggested by Corren (7).  He uses the definition of endotype as "a subtype of a condition defined by a distinct pathophysiological mechanism."  The classification was a consensus of experts looking at clinical characteristics, biomarkers, lung physiology, genetics, histopathology, and treatment response.  The following 5 endotypes were identified.

Asthma Endotypes
Allergic Asthma
Childhood onset, hypersensitivity to airborne allergens, Th2 mediated inflammatory process, eosinophilia of blood and airways, inhaled corticosteroids less effective, IgE antagonists are more effective. 
Aspirin exacerbated respiratory disease (AERD)
Chronic rhinosinusitis with nasal polyps, severe bronchospasm if NSAIDs are ingested, marked blood and airway eosinophilia, increased expression of leukotriene C4 synthetase, response to cysteinyl leukotriene receptor antagonists and 5-lipoxyenase inhibitors  
Allergic bronchopulmonary mycosis (ABPM)
Colonization of airways by Aspergillus fumigatus, increased fungal specific IgE and IgG, elevated blood eosinophil and total IgE levels, elevated airway eosinophils and neutrophils, requires oral corticosteroids and antifungals
Late Onset Asthma
Pulmonary function testing is more impaired than allergic asthma, marked eosinophilia in blood and airways, need oral corticosteroids.  May be mediated by IL-5.  
Cross country skiing induced asthma (CCSA)
Triggered by exposure to cold dry air and intense exercise, not usually due to allergies, inflammatory infiltrate consists of lymphocytes, macrophages, and neutrophils rather than eosinophils,  airway remodeling with thickened basement membrane, not usually responsive to inhaled corticosteroids.

The tables on diagnosis and endophenotype are remarkable for their parallels with psychiatric diagnosis and research.  The available endotypes do probably not capture all of the clinical scenarios of asthma because patient behavior is a significant factor.  The endotype classification of asthma by experts is interesting in that it includes a treatment response dimension and this has been avoided in psychiatry at the diagnostic level.

Like mental illnesses, asthma is a complex polygenic disease with considerable clinical heterogeneity.  Using endophenotype approaches very similar to the approaches that have been applied to the study of schizophrenia offers the hope that classification and treatments of subtypes will be more effective and the connection between the genetics of the illness, pathophysiological mechanisms, and subtype will become more apparent.  Although the parallels with mental illness are clear, asthma researchers and clinicians treating asthma have the advantage in that they can proceed without the stigmatization that only accompanies psychiatric disorders and psychiatrists.

George Dawson, MD, DFAPA




1: Barranco P, Pérez-Francés C, Quirce S, Gómez-Torrijos E, Cárdenas R, Sánchez-García S, Rodríguez-Fernández F, Campo P, Olaguibel JM, Delgado J; Severe Asthma Working Group of the SEAIC Asthma Committee. Consensus document on the diagnosis of severe uncontrolled asthma. J Investig Allergol Clin Immunol. 2012;22(7):460-75; quiz 2 p following 475. PubMed PMID: 23397668.

2: Simon T, Semsei AF, Ungvári I, Hadadi E, Virág V, Nagy A, Vangor MS, László V, Szalai C, Falus A. Asthma endophenotypes and polymorphisms in the histamine receptor HRH4 gene. Int Arch Allergy Immunol. 2012;159(2):109-20. doi: 10.1159/000335919. Epub 2012 May 30. PubMed PMID: 22653292.
3: Matteini AM, Fallin MD, Kammerer CM, Schupf N, Yashin AI, Christensen K, Arbeev KG, Barr G, Mayeux R, Newman AB, Walston JD. Heritability estimates of endophenotypes of long and health life: the Long Life Family Study. J Gerontol A Biol Sci Med Sci. 2010 Dec;65(12):1375-9. doi: 10.1093/gerona/glq154. Epub 2010 Sep 2. PubMed PMID: 20813793; PubMed Central PMCID: PMC2990267. 

 4: Bisgaard H, Bønnelykke K. Long-term studies of the natural history of asthma in childhood. J Allergy Clin Immunol. 2010 Aug;126(2):187-97; quiz 198-9.  doi: 10.1016/j.jaci.2010.07.011. Review. PubMed PMID: 20688204. 

5: Chan IH, Tang NL, Leung TF, Huang W, Lam YY, Li CY, Wong CK, Wong GW, Lam CW. 
Study of gene-gene interactions for endophenotypic quantitative traits in Chinese asthmatic children. Allergy. 2008 Aug;63(8):1031-9.
doi: 10.1111/j.1398-9995.2008.01639.x. PubMed PMID: 18691306. 

6: Thompson MD, Takasaki J, Capra V, Rovati GE, Siminovitch KA, Burnham WM, Hudson TJ, Bossé Y, Cole DE. G-protein-coupled receptors and asthma endophenotypes: the cysteinyl leukotriene system in perspective. Mol Diagn Ther. 2006;10(6):353-66. Review. PubMed PMID: 17154652.

7. Corren J. Asthma phenotypes and endotypes: an evolving paradigm for classification.
Discov Med. 2013 Apr;15(83):243-9. PubMed PMID: 23636141.

8. Bel EH. Clinical Practice. Mild asthma. N Engl J Med. 2013 Aug 8;369(6):549-57.
doi: 10.1056/NEJMcp1214826. PubMed PMID: 23924005