Saturday, October 10, 2015

Current Treatment of Respiratory Viruses - More Homilies






With Permission: SIB Swiss Institute of Bioinformatics,

Philippe Le Mercier, ViralZone.


My Facebook feed got me going today.  I get the Mayo Clinic feed since I consider their clinical care and some of their research to be the best in the world.  Of course social media is much less rigorous and sometimes it comes down to just advertising and promotion.  That was my assessment of the link to this document this morning.  It is a business document that purports to give advice on how to decrease your chances of a respiratory infection this winter.  Some of that advice is given by a Mayo Clinic Infectious Disease specialist and a Cleveland Clinic family physician.  There was one number I had not seen before and that is the Number Needed to Treat (NNT) for the flu vaccine is 40.  Forty people need to be vaccinated to prevent one case.  The advice is the usual set of homilies about respiratory infections including get the flu vaccination, wash your hands, sneeze into your sleeve, take care of yourself and stay home of you are sick.  In other words, there is no way in hell that you are not going to get sick at least once this winter.

Our continued 1950's approach to viral infections remains a mystery to me.  Certainly there are technical problems with trying to design vaccines for over 200 viruses that can cause the common cold.  But the reality is, vaccine design for influenza virus - easily the most lethal of these viruses is obviously not so hot.  As far as I know, vaccines for the most common of the cold viruses - Rhinovirus - is non-existent.  Anti-viral medications for respiratory viruses are more controversial.  Looking at the most popular one Tamiflu or oseltamivir.  The NNT to prevent one death may be 1,800 - 3,200.  The NNT to prevent one hospitalization may be 97 to 142 depending on criteria.  The NNT group suggests somewhat better NNTs of 36 and 83 for preventing a culture positive case of influenza and preventing pneumonia respectively.    Contrast that with the NNT for antidepressants of 5-10 as determined by Leucht, et al (2) in their comparison to other medications for various medical conditions.  And you thought antidepressants were ineffective?

Infectious disease respiratory virus research is a goldmine for all of the Luddites out there.  There are a number of web sites that provide free access to just about everything you ever wanted to know about every virus known to man.  The viral particle shown at the top of this page is the order that contains Rhinoviruses one of many common cold viruses and one of the viruses that may be responsible for the expression of asthma in predisposed individuals or exacerbations of asthma in asthmatics who are asymptomatic.   This illustration is from the ViralZone, one of many free online databases with detailed information about the molecular biology and genetics of viruses.  If I was an aspiring Luddite wanting to be provocative about the field of medicine being stuck in the 1950s despite the availability of all of this advanced information - this would be a logical place to start.

In previous posts here I have also critiqued the lack of attention given to environmental approaches to respiratory viruses and the fact that the airborne nature of some of these viruses is not acknowledged - possible because airborne viruses are not contained by hand washing and other direct contact techniques.  It s well know that viruses can be collected in the heating and air conditioning systems of public buildings and that altering the humidity and air flow characteristics in those buildings can change the viral concentrations in the air.  Whenever I have mentioned this to the administrators of buildings where repeated respiratory epidemics swept through the staff - I got the same response that I received from an airline after I reported a severe respiratory infection after one of their flights: "We are really sorry that you had flu-like symptoms after your flight and look forward to your future comments to help us improve our service."

What?!

 Time to get serious about respiratory infections and come up with some effective interventions.  Effective medication to prevent viral replication and spread in the infected and to create barriers to infection would be ideal and so would environmental methods to reduce the infection rate.  Considering the strong incentives in America to work while sick and considering that the average worker is going to get 2 to 3 respiratory infections per year that can last up to 3 weeks in duration means that very few of us and the patients that we treat are not going to be exposed and infected.  With the current advanced knowledge of the pathogens and modern heating and air conditioning systems it seems like a lot more could be done right now.


George Dawson, MD, DFAPA


References:

1:  Postma MJ.  Re: Tamiflu: NNT to prevent a pandemic flu death may be a million.  BMJ 2005; 331:1203.

2:  Leucht S, Hierl S, Kissling W, Dold M, Davis JM. Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. Br J Psychiatry. 2012 Feb;200(2):97-106. doi: 10.1192/bjp.bp.111.096594. Review. PubMed PMID: 22297588.


Attributions:

Graphic at the top of this post is courtesy of: SIB Swiss Institute of Bioinformatics, Philippe Le Mercier, ViralZone.  http://viralzone.expasy.org/  licensed via Creative Commons Attribution- NonCommercial 4.0 International License.

Does Publicizing Mass Shooters Benefit Anyone?





I ran across this perspective posted on the Kottke blog.  It is basically a journalist writing an opinion piece about why the names of mass shooters should be used in the media.  I think it is a reaction to the banning of the use of the names and details of mass shooters by some law enforcement and the media.  The Sheriff in the most recent mass shooting incident refused to release the name of the shooter.  The argument against releasing the name of the shooter goes something like this.  At least part of the motivation of some of these shooters involves the fame and publicity that they will achieve based on the incident.  The mass shooting incidents have been in my estimation fairly compared to terrorist incidents where the victims are killed in some of the most horrible and sadistic ways possible as part of the media campaign by these organizations.  It enhances any kidnaping and extortion threats that they may have and also enhances their image as a ruthless and single-minded entity.  Until recently that behavior was also a ticket to widespread international media exposure.  When the media cycle becomes knee jerk in response to mass shootings or terrorist events it is predictable no-cost publicity to both types of perpetrators.

There is additional evidence in the personal effects of many of these shooters and well as evidence from the staging of the events that publicity is a strong motivating factor.  The shooters often have computers and written statements about the motivation for their acts, and some of that material describes the event as something for the world to see.

The counterargument from the journalist seems to be that it is important for the public to hear all this information.  He makes the expected argument of the press that all of the news needs to be reported.  He also spins the political angle and suggests that conservative gun advocates including the sheriff involved in the most recent incident and then Fox News have elected not to name the perpetrator and connects this with the right wing tendency to talk about mental illness being the problem and not uncontrolled access to firearms.

I am at the point where I cringe when reading these highly politicized arguments probably because that is all that I hear when it comes to psychiatry.  The general form of the argument is that people taking a certain position have a certain ideology and therefore the conflict of interest issue reigns supreme.  Because a news service or a sheriff have been identified as being right wing and supporters of continued open access to firearms, anything they say about maintaining the anonymity of the perpetrator can be discounted based on conflict of interest.  In other words, by maintaining the anonymity of the shooter and focusing on the mental state of the shooter, the focus is shifted inappropriately away from more functional legislation to reduce firearm access.  The writer acknowledges that part of the motivation of some of these shooters is publicity or infamy whether they survive or not.  It is hard to deny because a review of the personal effects of some of these shooters makes it explicit.  The author takes the view that denying this publicity essentially gives the appearance that something is being done and this is bullshit.

First off, that does not meet my definition of bullshit from the definitive essay by Frankfurt.  According to Frankfurt, the main differentiating point between bullshitters and liars is that bullshitters have a blatant disregard for the truth.  The truth in this case is that irrespective of political motivations it is highly likely that denying these men the publicity that they seek will result in fewer of these crimes.  It might even provide a public health path to treatment for many of these individual instead of acting out.  I would suggest statutes that address the issue of how mass shooters should be handled in the event of any incident and would not only see anonymity as being important, but also confiscating property and all of the written material and images from the perpetrator and making them available for academic study, but not for the evening news.

The author also seems blind to the role of journalists in this process.  Every massacre triggers the standard response from journalists that I have written about on this blog many times.  All of the shocking details, the interviews with the aggrieved, the response from politicians, and the "profiling" of the perpetrator.  Then after a few days, the President comes on and we are all told to move on.  It seems that the President in his latest address has questioned the value of this process before members of the press have including this author.

My conclusion is that there has to be obvious progress in the area of gun control (yes - I said control).  But I have also accepted the fact that the power structure in this country does not have to yield to public opinion.  My decades of treating violent and aggressive people have also led me to understand that this is also a public health problem and as a public health problem - multiple measures need to be in place.   Restricting wide spread publicity for the perpetrators is one of many logical options.

There is also the issue of contagion.  Does a large incident with a lot of news coverage trigger copycat crimes?  There have been some anecdotal reports that copycat crimes occur in the specific area of school shooting.  The authors of a recent PLOS article (2), analyze the USA Today Mass Killing database and the the Brady Campaign School Shooting database.   The original databases and any modifications to them are available at this link.  The authors comment that a contagion model has been applied to several natural events like the financial markets, burglaries and terrorist attacks.  The authors specify the model they are using and go on to show that according to the USA Today database there was a mass killing (involving 4 or more people killed) every 12.5 in the US.  For the Brady database school sooting occurred every 31.6 days.  The authors illustrate there is a contagion effect for mass killings involving firearms but not mass killings that do not involve firearms.  They also show correlations between state prevalence of firearm ownership and mass shootings, but the authors note that mass shooters commit suicide 48% of the time and that is much higher than the expected suicide rate by perpetrators committing a single act of homicide (5-10%).  Mass shooters who commit suicide also kill 22% more people than mass shooters who do not.  The graphics and statistics in this article are great and I highly recommend a look at the graphs showing what part of the data is due to the contagion effect.  I also applaud the authors efforts to publish essentially public health research in an area that has been actively suppressed by Congress.  Scientific research on firearms policy is apparently incompatible with the Second Amendment.

So it turns out that there are probably legitimate reasons for withholding the identity of mass shooters and decreasing the disclosures about the incident and in some cases the audiovisual material that they have produced to promote their activity.  There is a well known journalistic tendency to wrap themselves in the flag when it comes to their not having complete access and the ability to disclose information, but the process is far from perfect and in many cases they defer to national security.   In the case of the databases involved there is clear asymmetry in terms of which incidents get publicity and which do not.  This is an opportunity for them to provide some news about public health interventions to prevent violence and mass shootings.

I don't think the importance of the notoriety or contagion factors in motivating mass shooters can be cancelled out by a conflict of interest argument.  But the conflict of interest card seems to be played like it is the trump card these days.

I also don't accept the "we as a society have made our choice" argument.  It's not really them it is us.  That argument is a stark contrast to how our government runs.  "We" are no more responsible for a society flush with guns that "we" were for three unnecessary wars based largely on fictional threats.  That oligarchy can function primarily with the full cooperation and lack of critical analysis by the American press.  The fact that late night comedians can produce more analysis of these issues than mainstream journalists is an indication of how much serious reporting is lacking.

There is probably no better example of reporting deficiency than how mass shooting incidents have been handled for decades.


George Dawson, MD, DFAPA


1:  Josh Marshall.  The Great Evasion.  TalkingPointsMemo.com  October 2, 2015.

2:  Towers S, Gomez-Lievano A, Khan M, Mubayi A, Castillo-Chavez C. Contagion in Mass Killings and School Shootings. PLoS One. 2015 Jul 2;10(7):e0117259. doi: 10.1371/journal.pone.0117259. eCollection 2015. PubMed PMID: 26135941.



Sunday, October 4, 2015

The Problem With Benzodiazepines.....




I want to thank David Allen for the inspiration for this post when he commented that as an addiction psychiatrist, I was probably seeing a skewed sample of people addicted to benzodiazepines and that might be why I have such a jaundiced view of them.  I use the above bubble diagram to illustrate how benzodiazepines are prescribed by docs like me with a strong bias toward preventing addiction compared with physicians who have no such bias.  To make sure that we are on the same page, benzodiazepines are all technically tranquilizers or sedatives.  They marked a therapeutic advance from the earlier barbiturate class  in that their therapeutic index (ratio of the drug that produces toxicity in 50% of patients to the dose that produces a therapeutic response in 50% of patients) is much greater than earlier tranquilizers like barbiturates.  The practical measure is that it takes much higher doses to produce respiratory arrest and death.  Despite the increased safety these drugs are addictive.  People can develop a tolerance and in some people they produce a euphorigenic effect, very similar to the effect of alcohol.  Some people describe benzodiazepines as "alcohol in a pill."  Unfortunately we do not know the percentage of people where that occurs or how to detect them. There are many common clinical situations where the safety margin of benzodiazepines is cancelled out by other factors.  Mixing them with alcohol and opiates are two of the most common dangerous situations and if you are treating addiction - you see that happen all of the time.

Rather than list the entire table of benzodiazepines, I am going to list the commonest ones that I see being abused.  In order from the most frequently abuse that group would include alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), and diazepam (Valium).  Of those compounds Xanax Bars or 2 mg alprazolam tablets seem to be the most commonly abused by far.  The maximum recommended dose of alprazolam is 4 mg/day and I frequently have seen people taking 8-20 mg/day in combination with other street drugs.  Benzodiazepines have all been generic for a long time so they are very inexpensive to purchase if you have a prescription.  If you don't have a prescription and acquire them illegally the "street value" of a drug is a sign of abusability.  The average street value of alprazolam is about $5 for a 2 mg bar.  The immediate risk of using benzodiazepines excessively is accidentally overdosing on the single drug or in combination with alcohol and other drugs of abuse.  There is also a significant seizure risk from abrupt withdrawal when the supply of medications have been used.  The abuse of benzodiazepine like compounds that are more typically used for sleep like zolpidem (Ambien) or eszopiclone (Lunesta) does happen but it is more likely to occur in combination with alcohol for alcohol related insomnia.  A common example would be a person with alcohol dependence who takes zolpidem at night so that they can sleep through the entire night.  Without it they would predictably wake up at 2 or 3 AM from the withdrawal effects of alcohol.  Chronic use of benzodiazepines whether by prescription or acquisition from illegal sources can lead to tolerance and chronic withdrawal symptoms that can last for months if the drug or medication is stopped.  That fact alone should be considered as part of the risk of taking benzodiazepines - even in the situation where the person does not have an addiction and has anxiety that they do not believe can be treated by any other means.  In my experience, I am not sure that kind of anxiety exists.

Another common problem with benzodiazepines is that they can be psychologically debilitating, even if the person affected never takes the pill.  It is all part of the behavioral pharmacology of addicting drugs.  It usually starts out with a panic attack.  That panic attack can result in people going to the emergency department once or twice because they believe they are having a heart attack.  Somewhere along the line a physician prescribes alprazolam to take "in case of a panic attack."  That starts to happen and even if the panic attacks are rare, brief, and situational - the person affected starts to believe they need to carry alprazolam around with them wherever they go "in case" of another panic attack.  They may not have had a panic attack in years, but they are more anxious about whether they are carrying a pill when they get on a plane, cross a bridge, etc.  The pill have taken on Talisman-like features based on their using it for a condition that for most people fades away over time.  Some  who don't know the sequence of events might suggest "what's the harm" if somebody develops such a belief system around a pill.  In my estimation the harm is that the person's normal conscious state has been transformed and they have exchanged one form of anxiety for another.  The debilitating effects of anxiety depend on the illusion that your life needs to be modified in a certain way to accommodate it.  Proving to yourself that is not true is one of the best ways to adapt.        

Despite those reservations, I have prescribed a lot of benzodiazepines in my career.  They are very good medications to use in controlled environments for acute alcohol and sedative hypnotic withdrawal, acute seizures, catatonia,  akathisia, and various agitation syndromes associated with acute psychosis and mania.  The goal is typically to get the patient off the medication before they are discharged and to avoid treating patients with addiction with benzodiazepines.  Benzodiazepines are also useful for the first month in treating panic attacks, but that typically takes a lot of work.  The work involved is convincing the patient that a medication that seems to work rapidly is not a good one to take for the long haul.  The other dimension that is operating here that is rarely commented on and never explicit is whether the person receiving the benzodiazepine enjoys taking it.  Medications that are potentially addictive lead to an array of problems that are not there with drugs than are not addicting.  The main one is that they tend to be viewed as solutions for everything.  Instead of just anxiety or panic people will take them for insomnia, stress, or just to wind down at the end of the day.  Medications that reinforce their own use have the problem of inventing new uses that they were never prescribed for and that can lead to escalating doses of the medication.  In some complicated situations benzodiazepines are added to treat anxiety.  They have been used in psychiatric patients with multiple problems and been shown to add no benefit.  They are commonly added to multiple medications including opioids in patients with chronic pain with no additional benefit.

Benzodiazepines are a big problem in primary care.  The NSDUH survey illustrates that most people with an addiction are not aware of it and further that only a small minority seek treatment and find it.  That same survey suggests that about 1.5 million Americans start using tranquilizers and sedatives (they do not have a unique benzodiazepine category) for non-medical use very year.  Even if it is apparent to a primary care physician and their patient that an addiction to benzodiazepines exits, there are significant obstacles to reversing the process.  Although there are protocols for slowly tapering the medication on the Internet, it takes a very highly motivated person and ideal circumstances to accomplish this.  Outpatient detox from urgent care, the emergency department or an outpatient clinic is problematic because the same medication that the patient is not able to control is being given to them to self administer at home.  It is common that the detox medications are all taken the same day or in some cases at once.  Structured detoxification in the American health care system is practically impossible to find, especially in the case of benzodiazepines that require careful attention to seizure prevention, the prevent of withdrawal delirium, and adequate treatment of chronic withdrawal symptoms when they emerge.  Some primary care clinics are taking the preventive approach of not starting benzodiazepines in the first place.


Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.



There is a lot of resistance to the ideas of addiction docs when benzodiazepines and their long term effects are discussed among physicians.  There is always a physician who claims that they have successfully treated a person with an alcohol use disorder with benzodiazepines or they have people who have stayed on low doses for decades in order to treat their anxiety.  I see the failures.  It leads to the question of how many people are capable of staying sober, not developing a tolerance to benzodiazepines, and not experiencing a negative impact on their life.

As far as I know there are no good studies that address that question and I would not expect that there will be.  Any study that allowed subjects to mix alcohol, opiates, and benzodiazepines would be unethical and should not be approved by any Human Subjects Committee.


George Dawson, MD, DFAPA


Supplementary:

This article was subsequently edited and modified for the Psychiatric Times.  The edited version reads better.

Friday, October 2, 2015

Is President Obama Reading This Blog?




Not really, but you can find the mass shooting links on this blog at this link.  They extend back three years and they overlap with a number of posts on homicide prevention.  They also overlap in many areas with the President's speech.  This was President Obama's 15th address to the nation following a mass shooting incident.  A couple of other landmarks - this was the 40th time this year that a gunman opened fire in a school and the 294th mass shooting incident this year.  Both of these markers illustrate how tragic but absurd this problem is in America.  How can responsible people allow this to happen?

The President is coming to the only logical conclusion that a person can come to about mass shootings and the relationship to firearms.  That point in this speech was when he said that our thoughts and prayers for the families and survivors are not enough.  We cannot keep making these pat statements in response to continuous mass shootings as though nothing can be done to prevent them.  We cannot treat mass shootings like they are routine:

"Earlier this year, I answered a question in an interview by saying, “The United States of America is the one advanced nation on Earth in which we do not have sufficient common-sense gun-safety laws -- even in the face of repeated mass killings.”  And later that day, there was a mass shooting at a movie theater in Lafayette, Louisiana.  That day!  Somehow this has become routine.  The reporting is routine.  My response here at this podium ends up being routine.  The conversation in the aftermath of it.  We've become numb to this."

 The familiar refrain about condolences to everyone and now it is time to move on needs to stop.  With governments that regulate what a lot of us do at work every day - right down to how we cross the Ts and dot the Is - it is difficult to believe that more functional gun control laws cannot be passed.  In his speech he points out that this is possible and there are laws that have been shown to work in other countries and in specific counties and municipalities in the United States.

At one point he speaks to the mind of the perpetrator:

"We don't yet know why this individual did what he did. And it's fair to say that anybody who does this has a sickness in their minds, regardless of what they think their motivations may be. But we are not the only country on Earth that has people with mental illnesses or want to do harm to other people. We are the only advanced country on Earth that sees these kinds of mass shootings every few months."

People tend to get hung up on whether specific perpetrators have a diagnosable mental illness and whether it is treatable.  They tend to get hung up on whether the behavior of violent individuals can be predicted over time.  They tend to be very pessimistic about the nature of the problem and whether insightless people will ever be able to get the kind of help that they need to prevent mass shootings.  It might be easier if there was some education about the types of situations that lead to these problems and the fact that in most of those cases, help is available.  That specific help will prevent homicides and prevent the unnecessary loss of lives of both the perpetrators and the victims.  

The President ended with a comment on the political process and an appeal to gun owners on the issue of whether they are being supported on this issue by an unnamed organization or not.  It was a compelling speech and the arguments are powerful.  As a politician, he is focused on political action and on common sense gun safety laws.  I have stated that it might be best to proceed from a public health standpoint and a focus on violence prevention and forget about legal approaches largely because there has been no political will on this issue.  President Obama has given one of the most compelling speeches on this issue that I have ever witnessed and it will be interesting to see the result.

From the medical and psychiatric side, our advocacy still needs to be on the public health side of the equation.  For me that comes down to seeing the problem to a significant extent as violence and homicide prevention.  We need more public education on the predisposing mental states and how to get assistance when these states are recognized.




George Dawson, MD, DFAPA


References:

Statement by the President on the Shootings at Umpqua Community College, Roseburg, Oregon.  October 1, 2015.  Transcript

Monday, September 28, 2015

High Intensity Movement Disorders Conference


I have been a member of the Movement Disorder Society since 1993.  I decided to join after having nothing but positive experiences at the annual Aspen courses led by Stanley Fahn, C. David Marsden, and Joseph Jankcovic.   Although Dr. Marsden has passed away, the course is still being given by two of the original lecturers with additional faculty.  The level of scholarship and expertise in this conference is really not approached by many venues these days.  Each conference provided participants with a 700 page textbook like syllabus on everything that you ever wanted to know about movement disorders.  Once you attend a conference like this it is a life transforming event.  Suddenly you are following the lecturers, you read what they write and you acquire some of their books.  I changed my Neurology text to Neurology in Clinical Practice because both Jankcovic and Marsden were editors.  I also received the video material and text of Movement Disorders,  the official journal of the International Parkinson and Movement Disorder Society.

People often ask why I am member of what is predominantly a neurological society?  In Minnesota there were only three psychiatrists who were members of the organization. Stan Fahn asked me that himself at one of the conferences.  I don't remember exactly what I said, but he thought my answer at the time was acceptable.  It comes down to clinical expertise and with the confluence of the dorsal and ventral striatum - neuroanatomy.  Back in the days that I went to medical school, nobody talked about the ventral striatum only the dorsal striatum and even back then, the main clinicopathological correlate was movement disorders.  As medical students we learned primarily about Huntington's Disease, Wilson's Disease, and Parkinson's Disease.  Nothing at all about dystonias or other disabling movement disorders and their treatments.  Nothing about the last members of the generation afflicted by what we called in those days post-encephalitic Parkinson's and all of the associated neuropsychiatric morbidity.   In my rotations at Milwaukee County Hospital and affiliated institutions I saw all kinds of undiagnosed or poorly diagnosed movement disorders.   There were no movement disorder specialists in those days and no treatments except for Parkinson's.  The quality of care is slightly improved today in that referral to movement disorder specialists and an appropriate diagnosis can occur, but the total number of these specialists is very small.

That is where psychiatrists need to fill in the gap.  My initial interest was tardive dyskinesia and describing the motor disorders of patients who in many cases had never been exposed to a medication.  But it quickly became recognizing the early manifestations of idiopathic and iatrogenic movement disorders and using these diagnoses in a comprehensive diagnostic approach to the patient as well as the treatment plan.  When you take that approach it is an eye opener.  In my role as a consultant it is amazing how much undiagnosed movement disorder pathology is out there.  A couple of examples will illustrate the problem.  About 50% of young adults with childhood diagnoses of Attention Deficit-Hyperactivity Disorder (ADHD) who have been treated with stimulants have a movement disorder usually in the form of vocal tics, motor tics, or Tourettes.  About 100% of those patients tell me that nobody has ever told them about those diagnoses before.  Of course there is an exhaustive list of medication and environmental exposures that can lead to tic disorders, so there is a question of whether something occurred since childhood.  In the same population there are a group of people with choreiform movements and predominately extensor muscle tone.  They are not aware of the movement disorder and nobody has mentioned it before.  It is as though clinicians consider these movements to be part of ADHD.  One of my observations about tardive dyskinesia has been that the overall prevalence of the disorder has dropped off significantly with the advent of atypical antipsychotic medication.  That does not mean that is has gone to zero and the augmentation of antidepressants with aripiprazole seems to be a new source of that disorder.  Most significantly, the people who are at greater risk for the problem do not seem to have been carefully screened ahead of time.  They are not routinely assessed for akathisia or other early motor symptoms like micrographia, diminished arm swing,  or hypophonia.

The course was presented by three neurologists Cynthia Comella, MD; Rajesh Pahwa, MD; and Jerrold L. Vitek, MD, PhD.  It was presented by the University of Kansas Medical Center and all of the brochures and specific courses are available on this web site.  The course was unusual in its rapid presentation of topics and strict adherence to that schedule.  There were ten presentations by the faculty varying in length from 20 to 55 minutes in duration.  The morning presentations covered Parkinson's and Parkinsonism, Restless Leg Syndrome, Tremor Disorders, and Movement Disorders in Psychiatry.  The afternoon covered Dystonia, Chorea, Tics, Neurotoxin and Deep Brain Stimulation for Neurological and Psychiatric Disorders.  The entire set of PowerPoints (without the videos) was included in the course syllabus.  The slides were all very readable in a standard format.  The Psychiatric Aspects of Movement Disorders was a very interesting presentation because it covered a wide range of problems that acute care and geriatric psychiatrists come in contact with including Parkinson's Disease and the associated psychiatric comorbidity, Tardive Dyskinesia, Neuroleptic Malignant Syndrome, Serotonin Syndrome, and Psychogenic Movement Disorders.  Interest in these topics may reflect exposure to the problem.  In seeing patients with Parkinson's and psychosis for example one of the commonest problems is that antipsychotic medications will generally make their psychosis worse.  The only exception to that is clozapine and that comes with a host of comorbidities and monitoring issues itself.  One of the presenters suggested that quetiapine is a default choice in many cases even though it is not ideal and efficacy is low.  A new medication for the treatment of psychosis in PD was mentioned called Pimavanserin.  It is a selective serotonin 5-HT2A inverse agonist without significant activity at dopaminergic, histaminergic, muscarinic, or adrenergic receptors.  Practical approaches to treating dementia, anxiety, and depression associated with PD were also discussed.

The most fascinating part of the course was the section on deep brain stimulation (DBS).  A fairly detailed description of the procedure was given.  Deep brain stimulation is currently FDA approved for Essential tremor and Parkinsonian Tremor and Parkinson's Disease with humanitarian device exceptions for Primary Dystonia and Obsessive Compulsive Disorder.  This section was presented by Dr. Vitek who has a wide range of experience with this method.  Before and after videos of children and adults with disabling movement disorders were presented and the results were striking.  The general concept presented was that any "circuit disorder" was a potential candidate for DBS and that is consistent with the current literature on the subject.  The other important concept is that with DBS there are no permanent changes in the brain apart from the low risk of placement complications.  That is not true for neurosurgical techniques that have been used for the same neurological and psychiatric complications.  In the case of DBS the stimulator can be reprogrammed, turned on or off in a number of configurations, and turned completely off.  An unexpected benefit of the DBS presentation was a look at brain images from a 7 Tesla MRI scan.  The resolution of these images was incredible arguably as good as artistic renderings of brain anatomy.  Take a look at the side by side comparisons to what is currently clinically available.

Everything considered this was an excellent conference and I recommend it to anyone if it comes to your area.  I think it could be used by practicing psychiatrists who want to get up to speed on movement disorders, residents wanting to do the same thing, and psychiatrists studying for their boards in geriatric psychiatry.  It also raises a larger question of just what psychiatrists should be able to diagnose and treat?  What should they know at a theoretical level?  Based on my experience, psychiatrists seem to be the specialists that are most likely to be confronted with an undiagnosed movement disorder in patients who have seen primary care physicians or pediatricians.  Psychiatrists are also specialists who should be the experts in how to recognize and prevent motor complications of medications used to treat psychiatric disorders.  Psychiatrists have also been using the same interview and mental status exam technology for the past 50 years.  Changes need to be incremental and the logical first change that seems in order is to be able to recognize, diagnose, and treat or refer movement disorders encountered in standard psychiatric practice.  Psychiatrists interested in neuroscience with also find this a very interesting area for ongoing study.  And subspecialists like geriatric psychiatrists are probably going to need to know the difference between tauopathies and synucleinopathies.

This course is a good one to get you on that road.


George Dawson, MD, DFAPA        


Attribution:  My own picture shot at the John Rose Oval in Roseville, Minnesota.



  

Sunday, September 27, 2015

Cochrane Distances Self from Critic





The Cochrane Collaboration came out with this press release to point out that one of their collaborators was posting his psychiatric criticism outside of his role in that organization.  The critic mentioned in this release has written this blogger in response to my critique of his criticism of psychiatry.  My response elicited a significant amount of derision directed at me from his apparent supporters.  That led me to modify my policy on posting comments. I believe that he posted a response to my response on another blog or blogs that I never read.

While I am no great supporter of Cochrane and consider their site to be somewhat redundant, non-productive, and lacking creativity and innovation, it is obviously in their interest to distance themselves from statements that they do not consider to be in their best interest.  For links to the exchanges on this blog with this critic, they are included in these two posts:

http://real-psychiatry.blogspot.com/2014/02/an-obvious-response-to-psychiatry-gone.html

http://real-psychiatry.blogspot.com/2014/02/the-proud-critics-of-psychiatry.html

Apart from the obvious, the more I thought about the last sentence in this release, the more it bothered me:

"There is a wide range of views within Cochrane on the benefits and harms of psychiatric drugs...."

That is an interesting perspective from an organization that is supposed to objectively interpret the evidence.  Are there an equally number of "wide range of views" on other types of medication or just the ones used by psychiatrists?  It leads to questions about whether there are psychiatric experts and people who actually prescribe the medications writing these reviews or if anyone can do it?  I could make the argument that many if not most of the summary statements seem like they are written by the same person or committee.  It also leads to the question about the political nature of these documents.  Could the specified critic for example reformulate his criticism according to the Cochrane format and publish it in their library?  Are Cochrane documents ever a compromise of a "wide range of views"?  Is there anyone at Cochrane who is aware of the additional levels of criticism that psychiatric practice is subject to and the rhetorical nature of that criticism?  I think that these are all important questions if you are concerned about being perceived as having a partisan position.  Of course most critics of psychiatry could care less about being partisan or even the appearance of being partisan, but they are generally not selling objective analysis.

Just this year, I lost access to a library database that I had previously accessed for years. I had to try to access Cochrane Reviews directly through a large publisher's web site. I was confronted with the prospect of purchasing the individual articles or an entire year long subscription through that publisher. They also have an open access model where authors can pay significant fees to have their articles published in an open access mode.   The Cochrane Library is a published product just like anything else, subject to all of the conflicts of interest of a published product.

That is an additional perspective to have when reading the release.


George Dawson, MD, DFAPA

Sunday, September 20, 2015

Ioannidis - Why His Landmark Paper Will Stand The Test of Time















John P. A. Ioannidis came out with an essay in 2005 that is a landmark of sorts.  In it he discussed the concern that most published research is false and the reasons behind that observation (1).  That led to some responses in the same publication about how false research findings could be minimized or in some cases accepted (2-4).  Anyone trained in medicine should not find these observations to be surprising.  In the nearly 30 years since I have been in medical school - findings come and findings go.  Interestingly that was a theory I first heard from a biochemistry professor who was charged with organizing all of the medical students into discussion seminars where we would critique research at the time from a broad spectrum of journals.  His final advice to every class was to make sure that you kept reading the New England Journal of Medicine for that reason.  Many people have an inaccurate view of science, especially as it applies to medicine.  They think that science is supposed to be true and that it is a belief system.  In fact science is a process, and initial theories are supposed to be the subject of debate and replication.  If you look closely in the discussion of any paper that looks at correlative research, you will invariably find the researchers saying that their research is suggestive and that it needs further replication.  In the short time I have been writing this blog asthma treatments, the Swan Ganz catheter, and the diagnosis and treatment of acute bronchitis and acute chronic obstructive pulmonary disease are all clear examples of how theories and research about the old standard of care necessarily change over time.  It is becoming increasingly obvious that reproducible research is in short supply.

Ioannidis provided six corollaries with his original paper.  The first 4 regarding power, effect size, the greater the number of relationships tested, and the greater the design flexibility are all relatively straightforward.  The last two corollaries are more focused on subjectivity and are less accessible.  I think it is common when reading research to look at the technical aspects of the paper and all of the statistics involved and forget about the human side of the equation.  From the paper, his 5th Corollary follows:

"Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true. Conflicts of interest and prejudice may increase bias, u.  Conflicts of interest are very common in biomedical research [26], and typically they are inadequately and sparsely reported [26,27].  Prejudice may not necessarily have financial roots.  Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings.  Many otherwise seemingly independent, university-based studies may be conducted for no other reason than to give physicians and researchers qualifications for promotion or tenure.  Such non-financial conflicts may also lead to distorted reported results and interpretations.  Prestigious investigators may suppress via the peer review process the appearance and dissemination of findings that refute their findings, thus condemning their field to perpetuate false dogma. Empirical evidence on expert opinion shows that it is extremely unreliable [28]"  all from Reference 1.

The typical conflict of interest arguments that are seen in medicine have to do with financial conflict of interest.  If the current reporting database is to be believed they may be considerable.  A commentary from Nature earlier this month (5) speaks to the non-financial side of conflicts of interest.  The primary focus is on reproducibility as a marker of quality research.  They cite the facts that 2/3 of members of the American Society for Cell Biology were unable to reproduce published results and that pharmaceutical researchers were able to reproduce the results from 1/4 or fewer high profile papers.  They cite this as the burden of irreproducible research.  They touch on what scientific journals have done to counter some of these biases, basically checklists of good design and more statisticians on staff.  That may be the case for Science and Nature but what about the raft of online open access journals who not only have a less rigorous review process but in some cases require the authors to suggest their own reviewers?  A central piece of the Nature article was a survey of 140 trainees at the MD Anderson Cancer Center in Houston, Texas.  Nearly 50% of the trainees endorsed mentors requiring trainees to have a high impact paper before moving on.  Another 30% felt pressured to support their mentors hypothesis even when the data did not support it and about 18% felt pressured to publish uncertain findings.  The authors suggest that the home institutions are where the problem lies since that is where the incentive for this behavior originates.  They say that the institutions themselves benefit from the perverse incentives that lead to researchers to accumulate markers of scientific achievement rather than high quality reproducible work.  They want the institutions to take corrective steps toward research that is more highly reproducible.

One area of bias that Ioannidis and the Nature commentators are light on is the political biases that seem to preferentially affect psychiatry.  If reputable scientists are affected by the many factors previously described how might a pre-existing bias against psychiatry, various personal vendettas, a clear lack of expertise and scholarship, and a strong financial incentive in marshaling and selling to the antipsychiatry throng work out?  Even if there is a legitimate critic in that group - how would you tell?  And even more significantly why is it that no matter what the underlying factors - it seems that conspiracy theories are the inevitable explanations rather than any real scientific dispute?  Apart from journalists, I can think of no group of people who are more committed to their own findings or the theory that monolithic psychiatry is the common evil creating all of these problems than the morally indignant critics who like to tell us what is wrong with our discipline.  Knowing their positions and in many cases - over the top public statements why would we expect  them sifting through thousands of documents to produce a result other than the one they would like to see?  

I hope that there are medical scientists out there who can move past the checklists suggested to control bias and the institutional controls.  I know that this is an oversimplification and that many can.  Part of the problem in medicine and psychiatry is that there are very few people who can play in the big leagues.  I freely admit that I am not one of them.  I am a lower tier teacher of what the big leaguers do at best.  But I do know the problem with clinical trials is a lack of precision.  Part of that is due to some of Ioannidis' explanation, but in medicine and psychiatry a lot has to do with measurement error.  Measuring syndromes by very approximate means or collapsing some of the measurements into gross categories that may more easily demonstrate an effect may be a way to get regulatory approval from the FDA, but it is not a way to do good science or produce reproducible results. 


George Dawson, MD, DFAPA




References:  

1:  Ioannidis JPA (2005) Why Most Published Research Findings Are False. PLoS Med 2(8): e124. doi:10.1371/journal.pmed.0020124

2:  Moonesinghe R, Khoury MJ, Janssens ACJW (2007)  Most Published Research Findings Are False—But a Little Replication Goes a Long Way. PLoS Med 4(2): e28. doi:10.1371/journal.pmed.0040028

3:  Djulbegovic B, Hozo I (2007)  When Should Potentially False Research Findings Be Considered Acceptable? PLoS Med 4(2): e26. doi:10.1371/journal.pmed.0040026

4:  The PLoS Medicine Editors (2005) Minimizing Mistakes and Embracing Uncertainty. PLoS Med 2(8): e272. doi:10.1371/journal.pmed.0020272

5:  Begley CG, Buchan AM, Dirnagl U. Robust research: Institutions must do theirpart for reproducibility. Nature. 2015 Sep 3;525(7567):25-7. doi: 10.1038/525025a. PubMed PMID: 26333454.