Viruses Are In The Air - Protection From Airborne Viruses

Today was a good day.  I got up this morning and there on the morning news was a headline that I had been waiting to hear for at least 20 years.  There on CBS This Morning, Gail King was saying: "The flu can spread just by breathing so that is kind of scary."  That is kind of scary.  It is even scarier if you know that fact and listen to 20 years of how hand washing will prevent the flu. Hand washing is good only for surface contamination.  It does nothing for airborne viruses.  There is no known protection from airborne viruses other than biohazard environments.

I did not come by the knowledge easily.  Before medical school, I was a research assistance in a plant tissue culture lab.  Our job was to try to clone Loblolly Pine (Pinus taeda) and Douglas Fir (Pseudotsuga menziesii) trees from elite seed.  That required a sterile environment for tissue and media manipulations.  I spent much of the day working in a laminar flow hood bathed in sterile air.  We were not concerned at all about viruses at the time, but there were always experiments lost due to yeast and fungal contamination of the culture medium.  From there it was off to medical school and observations about just how contagious airborne viruses could be.  On some rotations the entire team was ill with respiratory infections.  I notice there is some movement today on telling physicians to stay home if they are sick.  If all of the people who were sick on one of these teams stayed home - there would be nobody there to take care of patients.  I did work with one attending physician who wore a surgical mask in a medicine clinic as a barrier to viruses.  Today we know that these masks are ineffective in blocking viruses.

The real eye opener came in practice.  For over 20 years I worked in an inpatient environment that was designed in the 1960s.  According to the HVAC experts I have consulted with, the environments in those days were designed to preserve heat.  They were not designed to provide fresh air in a manner that would minimize the risk of airborne virus infections.  All of the rooms in that environment had individual radiators equipped with fans.  The room air was recirculated.  At the top of each room was a 12" x 12" square vent that moved the air down  the length of the building to a few air shafts that traveled up and down between floors.  I was reassured that there was adequate air flow and that it was measured.  I was provided with some diagrams that did not really show any solid data.

In that environment, airborne viral infections ran rampant.  They were acute care psychiatric units - so many of the patients directly admitted had influenza.  It was just a matter of time before it was picked up by the staff and then transmitted from person to person.  Getting one or more of these infections predictably was quite depressing.  As anyone knows - a severe case of the flu disrupts your entire life.  The polypharmacy that the staff was subjected to was also impressive.  Long complicated courses of antibiotics for secondary infections after the flu had passed.  Exposure to prednisone and methylprednisolone for post-viral bronchitis and asthma exacerbations.  All of the infected staff were schooled in proper handwashing techniques by Infection Control.  During flu season we were basically adrift in tight confines - breathing contaminated air.  It is well documented by studies in hospital and other building environments that there are a significant amount of viral and other pathogens in the air that can be collected by a number of means (2).

The other enlightening experience involved my participation in two Avian Influenza task forces.  Practically all of the work that I saw being done seemed to ignore the issue of airborne spread.  That was probably at least in part due to the fact that the hospital capacity of negative air pressure rooms would be immediately overwhelmed.  At that point, I heard one expert say: "You need to have an N95 respirator mask on as soon as you walk through the door of the hospital."  The efficacy of those masks in preventing flu transmission is limited but probably offers some moral support when you are walking into an environment that is full of highly lethal influenza virus. Most of the planning done on the task forces seemed to be designed to prevent a large surge of patients going to the emergency department, providing psychological support to the overwhelmed, and hoping the military really did have that palette full of Tamiflu that they keep showing us in the PowerPoint presentations.

One of the questions I frequently get is - what about the vaccine?  Designing an effective flu vaccine is part science and part speculation.  It involves anticipating the viral strains of the next epidemic and that is difficult to know with certainty.  This is the first year that I can recall public health officials coming out with the actual numbers.  Most Americans have heard that this years vaccine is about 30% effective and that the most effective vaccines are 50-60% effective.  The argument is that the vaccine improves herd immunity and decreases the spread of the virus.  Exactly how much of that is cancelled out by broad exposure to an airborne virus is unknown, but I do think that is sufficient reason to always get the vaccination.  I was my own experiment for about 30 years.  I reacted to an anti-rabies duck embryo vaccine in my 20s and did not get the vaccine for the subsequent years.  I finally saw an allergist/immunologist about 7 years ago and have been getting the vaccine since.  Since then there has been no detectable change in the number or intensity of flu-like illnesses that I have developed.  During the time unvaccinated, I had the experience of developing an acute fever after being exposed to a colleague with the flu, taking Tamiflu (oseltamivir) and having the symptoms resolve within 24 hours.  There is a chance that a universal flu vaccine can be designed and I hope that is true.  In the meantime we are left dealing a number of airborne viruses and altering the environment seems like the best approach.   

Flashing forward to this morning.  Part of the story focused on Donald K. Milton and the work he did in designing a machine to sample flu viruses in a natural setting.  Other sampling techniques have typically involved subjects breathing according to protocol into a device.  The large reverse megaphone type of device that this group is using allows air flow past the face at a regular rate.  It allows research subjects to breath normally and sample their expired air for influenza virus.  The sample in this case was a group of healthy 19-21 year old college students with a high asthma prevalence (21%) and a low influenza vaccination rate.  Nasopharyngeal (NP) sampling and RNA detection was used to diagnose influenza and RNA copies.

The subjects were asked to breathe, talk, cough, and sneeze into the sampling device with no constraints on that activity.  They were asked to recite the alphabet at 5, 15, and 25 minutes.  Coarse droplets (> 5 μm ) and fine droplets (≤ 5 μm and >0.05 μm) were collected separately. Influenza virus was recovered from 89% (N=150) of the NP swabs and 39% (N=52) of the fine aerosol sample. This is positive proof that just breathing (tidal volume breathing) results in dispersing infectious viral particles into the air.  The influenza cases did not sneeze during the collection period. Viral shedding was greater for men.  Women coughed more frequently but shed significantly less virus per cough.  Increased BMI produced increased viral shedding in the fine aerosol and the speculation was that increased BMI causes a tendency for small airway collapse and that may lead to increased shear forces that produce the fine aerosol.  Since sneezing was not observed - it was not considered necessary to produce the fine or coarse aerosol.  Coughing was present and was a significant predictor of both coarse and fine aerosols.

 
This is a critical paper that I hope that all public health officials, administrators and architects will take note of.  It takes more than handwashing and coughing into your sleeve to protect people against influenza virus.  It takes recognition that this is an airborne virus and it is aerosolized by breathing.  Physicians are on the front lines when it comes to virus exposure and we need better barrier methods to prevent exposure.  During flu season I sit in a 8 x 10 foot office and talk with people who sit about 4-5 feet away from me.  I talk with most of them for 20-30 minutes or about the length of time of the experiment.  The symptoms listed in the severity scale below are incorporated into my review of systems and there are some days when 100% of the people I see have a respiratory infection.  If they all have influenza, 30% will leave aerosolized virus in my office just from talking with me.  Is there a better way to do things to minimize exposure?

I think it starts with building design.  Rooms that are all individually vented to the outdoors on both the intake and exhaust side.  Heat exchangers exist today and can be used for this purpose.  Starting with influenza as the model and optimizing air flow and humidity to decrease infection rates is a start.  Interviewing people across barriers or using television cameras is another possibility especially if vulnerable populations need to be protected from consultants who may be carriers. The tremendous lack of psychiatric infrastructure compounds the problem.  Although the building that I refer to was ultimately replaced and torn down - psychiatric services are typically housed in the oldest and most run down buildings.  Today jails have replaced psychiatric hospitals and the jail infrastructure is no better.  It is common to see patients who are acutely ill with influenza in these settings.  Psychiatric beds need to be in an environment that reduces the transmission of infectious diseases including airborne viruses.   

The work does not stop at that level.  The ways hospitals and buildings are cleaned needs to be thoroughly investigated.  Carpet and floor cleaning equipment clearly leads to the dispersion of particles in the carpeting or on the floor.  I am not aware of any initiative to make sure that cleaning the surfaces in buildings does not leave the air contaminated.

My advice is to spread the word and this reference to anyone who is unsure about airborne viruses. I am hopeful that at some point over the next 10-20 years the environmental aspects of the problem will be addressed.  That will change the nature of influenza transmission as well as a host of other viruses that get sampled in the HVAC systems of old buildings - probably long after the occupants have been infected by them.



George Dawson, MD, DFAPA


References:


1:  Yan J, Grantham M, Pantelic J, Bueno de Mesquita PJ, Albert B, Liu F, Ehrman S, Milton DK; EMIT Consortium. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1081-1086. doi: 10.1073/pnas.1716561115. Epub 2018 Jan 18. PubMed PMID: 29348203; PubMed Central PMCID: PMC5798362

2:  Airborne Virus Monitoring: unedited search



Supplementary:

Image at the top uses a crowd infographic from Shutterstock per their licensing agreement.

Supplementary 2:

This is the approach the authors used to scoring the flu symptoms severity in their paper (my interpretation) (click to enlarge):

New Autism Drug - Balovaptan (RG7314) - A vasopressin V1a antagonist

Balovaptan (RG7314)

Autism is a difficult to treat disorder, especially in the case where it is associated with aggression.  As the patient ages, physical redirection and behavioral approaches can not be effective.  In that case, the patient's living situation can be placed at risk.  As an inpatient psychiatrist, I would frequently see patients admitted to my inpatient unit who had been living at home until their parents could not longer provide the necessary care.  The expectation was that the inpatient stay would help with that transition.  Care of the older person with autism and aggression is further complicated by a nearly complete lack of public resources in terms of stable living environments with staff present to assist with behavioral problems.

The only medications that have been FDA approved to treat autism are risperidone - the first approved atypical antipsychotic medication in the USA and aripiprazole.  Antipsychotics can exert an anti-aggression effect in the case where aggression is part of schizophrenia and bipolar disorder.  It is also used as an off label indication for treating aggressive symptoms in personality disorders and autism.  One of the main studies in autism was done by McCracken, et al (1) and published in 2002.  That study showed a significant improvement in irritability, aggression, and self injury in the treatment group relative to the control group.  In the study irritability as measured by that subscale on the Aberrant Behavior Checklist was significantly improved in 69% of the treated group and that improvement was maintained at 6 months.  The mean daily dose of risperidone was  1.8±0.7 mg to a group with a mean age of  8.8±2.7  years.  By comparison, the lowest effective dose in adults is 6 mg with typical range of 2-5 mg for most conditions.

The limitations of atypical antipsychotic therapy are well known and they were observed in this group of children over the course of the course of the 8 week study.  They included increased appetite, a weight gain of  2.7±2.9 kg, and drowsiness.  Of the neurological symptoms anticipated with this class of drug including akathisia, tremor, dyskinesia, rigidity, and difficulty swallowing - only the tremor was more frequently observed in the risperidone treated group relative to placebo.  The rate of withdrawal from the study was 5 times higher in the placebo treated group.  The authors concluded that within the limits of their study design that risperidone was safe and effective for the treatment of tantrums, aggression, and self injury.  The FDA package insert for risperidone was modified to include the indication:  Treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years.  FDA approval for risperidone was in 2006 followed by FDA approval for aripiprazole in 2009.  The wording in the package insert is slightly different under the indications section for aripiprazole:  Irritability Associated with Autistic Disorder.  Although I don't have any actual data, clinical use in adults suggests that aripiprazole would be the most prescribed agent for autism because it is generally seen as having a more favorable side effect profile.

The putative effects of psychiatric medications are generally extrapolated from know receptor affinities and atypical antipsychotics are generally dopamine receptor (D2) and serotonin receptor (5HT2) antagonists.  Aripiprazole is described as a partial agonist activity at D2 and 5-HT1A receptors and an antagonist at 5-HT2A receptors.   Because of the limitations of this class of medications other molecular targets have been sought.  Vasopressin and oxytocin and their receptor systems have become targets of interest by some research groups.

The best paper and the only paper (4) I was able to locate that was a comprehensive look at the research supporting this approach as well as the discovery path and synthesis of the ultimate chemical compounds is reference 4 below.  It happens to be authored by chemists from Roche, the company that has been awarded FDA breakthrough status for it newly approved autism drug - Balovaptan (RG7314).  Interestingly none of the 41 structures listed in the article matches the final structure given above.  The paper is a testament to modern medicinal chemistry - not so much on the synthesis end but how compounds are screened for activity at specific receptors.  All of the preliminary animal data point to the vasopressin G protein coupled receptor V1a.  A V1a antagonist was thought to have possible anxiolytic, antidepressant and pro-social properties.  Because of the similarity to oxytocin and potential candidate drug needed to not block V2 receptors mediating antidiuretic effects in the kidney and not counteract the prosocial effects of oxytocin.

       
The authors screened 700,000 compounds at a concentration of 10 μM and had a hit rate of 1.48% looking for an "orally available, CNS penetrant and selective V1a antagonist". They identified 8 compounds with suitable DMPK (drug metabolism and pharmacokinetics) parameters that might be suitable for human studies. From there they used a chemogenomics approach based on the assumption that proteins with similar binding sites similar ligands. They developed a list of human class A GPCRs (G-protein-coupled receptors). They used this approach to look at the 35 amino acids that form the transmembrane pocket for 298 GPCR receptor sequences.

At this time I cannot locate an FDA approved package insert for Balovaptan, more detailed information on its medicinal chemistry, or the details about the trial entitled  the VANILLA ( Vasopressin ANtagonist to Improve sociaL communication in Autism ) a phase II trial of Balovaptan.  I have located the author of a paper on the VANILLA trial that may have been associated with the drug getting approval and have requested that article.  I did locate the FDA podcast (7) that briefly discusses how Balvaptan may be a breakthrough drug for autism spectrum disorder because it might address the core social deficits of the disorder.  The podcast suggests that the company will not be filing for approval of the drug until 2020.

The only experimental data that I could find was a proof of mechanism study that basically looked at some purported measures of vasopression V1a antagonism (3,4).  The authors used a compound (RG7713) that is not the Balovaptan (RG7314) designation in a randomized, double blind, placebo controlled, two period crossover study of 19 subjects with high functioning autism.  The subjects had a mean age of 23 and a full scale IQ or 100.  A single 20 mg dose infusion over two hours was administered.  The subjects were tested on paradigms that looked at eye-tracking, affective speech recognition, reading the mind in the eyes (thought or mood) test, olfactory identification and scripted interactions to look at interpersonal skills.  They were also rated on global functioning and anxiety.

The only significant result was a change in eye tracking with the compound of interest.  The  global rating of improved function was slightly improved.  There were four adverse effects from RG7713 but not placebo.  There were no serious adverse effects or early terminations.

Based on the currently available information, the proof of concept paper for a similar vasopressin V1a antagonist provides modest proof at best.  As any clinician knows, in order to diagnose autism it requires not just a knowledge of the criteria, but clinical experience in observing autism.  There is a high degree of subjectivity.  In the popular media that has resulted in applying what appear to be diagnostic criteria to a number of very high functioning celebrities and concluding that they are on the autism spectrum.  Reading through the objective measures used in this paper is concerning and makes me question the validity of several of the tests.  I suppose the proof of concept at the pilot study level is justified by the eye tracking test since this is the single test with the most research in the disorder and it represents a clear clinically observed finding.  What I will be looking for in future papers or the VANILLA study paper if I can get it is a more robust demonstration of objective findings.  I think one of the best ways to do that is to use a stratified sample of subjects according to severity of the disorder.   

It is always disappointing when the press leads with a story like this and there is a data vacuum.  Let's hope they release some studies of Balovaptan and the package insert information, but that might not happen for a couple of years.


George Dawson, MD, DFAPA


References:

1:   McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002 Aug 1;347(5):314-21. PubMed PMID: 12151468.  DOI: 10.1056/NEJMoa013171

2: Umbricht D, Del Valle Rubido M, Hollander E, McCracken JT, Shic F, Scahill L, Noeldeke J, Boak L, Khwaja O, Squassante L, Grundschober C, Kletzl H, Fontoura P. A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder. Neuropsychopharmacology. 2017 Aug;42(9):1924. doi: 10.1038/npp.2017.92. PubMed PMID: 28701745; PubMed Central PMCID: PMC5520791.

3: Umbricht D, Del Valle Rubido M, Hollander E, McCracken JT, Shic F, Scahill L, Noeldeke J, Boak L, Khwaja O, Squassante L, Grundschober C, Kletzl H, Fontoura P. A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder. Neuropsychopharmacology. 2017 Aug;42(9):1914-1923. doi: 10.1038/npp.2016.232. Epub 2016 Oct 6. Erratum in: Neuropsychopharmacology. 2017 Aug;42(9):1924. PubMed PMID: 27711048; PubMed Central PMCID: PMC5520775. 

4: Ratni H, Rogers-Evans M, Bissantz C, Grundschober C, Moreau JL, Schuler F, Fischer H, Alvarez Sanchez R, Schnider P. Discovery of highly selective brain-penetrant vasopressin 1a antagonists for the potential treatment of autism via a chemogenomic and scaffold hopping approach. J Med Chem. 2015 Mar 12;58(5):2275-89. doi: 10.1021/jm501745f. Epub 2015 Feb 18. PubMed PMID: 25654260.

5: Albers HE. Species, sex and individual differences in thevasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network. Front Neuroendocrinol. 2015 Jan;36:49-71. doi: 10.1016/j.yfrne.2014.07.001. Epub 2014 Aug 4. Review. PubMed PMID: 25102443.

6: Francis SM, Sagar A, Levin-Decanini T, Liu W, Carter CS, Jacob S. Oxytocin andvasopressin systems in genetic syndromes and neurodevelopmental disorders. Brain Res. 2014 Sep 11;1580:199-218. doi: 10.1016/j.brainres.2014.01.021. Epub 2014 Jan 22. Review. PubMed PMID: 24462936; PubMed Central PMCID: PMC4305432.

7:  FDA Podcast:  074 – Roche’s balovaptan for autism; Lutathera for GEP-NETs; SyMRI NEURO for myelin quantitation on MRI; FDA approves human exoskeleton

The Luddites Are Always At The Gate

Prevalence of Multimorbidity with Age (left) and Sex (Right) from Reference 2 per Creative Commons Attribution License.

I noticed a Twitter feed about a blog piece on the complexity of multiple illnesses and the need for primary care (1).  If the post would have stopped there it would be impossible to disagree with.  Unfortunately in the usual manner of the blogosphere - for every group elevated another needs to pay the price.  In this case, the natural target would be the specialists.

The basic argument is that as people get older they end up with more chronic diseases. That should not be surprising to anyone - see the graphic above and click on it to enlarge.  People who accumulate more of these chronic illnesses are the most expensive people to care for in the health care system.  Also no surprise, but somewhat of an overstatement.  In the USA, it is quite easy to be sailing along disease free and suddenly develop an illness that places you in the top tier of treatment costs.  Cancer is a clear example.  One of my colleagues told me that the total cost of treatment for breast cancer in one of his relatives was over $1 million dollars.  That explains the main motivation for health insurance in the USA, any serious illness can lead to bankruptcy without insurance.

The argument continues that the predominate model of care is that physicians diagnose, treat, and cure illness in episodes of care rather than maintaining people with chronic illnesses.  The author concludes that physician specializing in organs or parts of organs are not equipped to deal with the problem.  He refers to remorseless specialization and subspecialization as being the problem.  He concludes that doctors and patients seem to be going in opposite directions because of this.

That is not what I am seeing.  In the USA, one of the main metrics followed in surgical specialties these days is the volume and outcomes of surgeries.  Several references point out that surgical volumes and good outcomes are directly correlated.  For that reason I found a neurosurgeon who was doing two transphenoidal pituitary adenoma resections per day for years rather than one who had done a total of 9 lifetime when my wife needed resection of a growth hormone secreting adenoma from her pituitary gland.  It has been 9 years since the resection and no recurrence of the tumor or endocrine markers.  She has not seen the surgeon again in that time but is followed by a primary care physician and an endocrinologist.
      
The beauty of the American health system if there is any is that you can see a broad array of specialists in any moderate population center.  The author was astonished to find that the British Journal of Ophthalmology has a different editor for every layer of the eye.  I think that it is equally astonishing that in most American cities you can wake up with symptoms of a retinal detachment and be seen by an eye specialist within hours. If it looks like you have a true acute retinal detachment - you will be referred to a retinal or vitreous specialist and have definitive treatment the same day or the next.  The laser surgical technique is far superior to what was being done 20 years ago and can be accomplished in an office in as little as 20 minutes.  That surgery prevents blindness and the need for riskier surgery.  Within a few decades, ophthalmology has evolved to a very effective and efficient specialty that covers a broad range of eye diseases with relatively few physicians.  The advantage of specialists in this case is clear cut and directly addresses patients needs.  In fact, the problems that ophthalmologists treat are barely addressed in medical schools.  The problem is not that the specialists don't know primary care.  The problem is that it is impossible for primary care physicians to recognize and diagnose eye conditions and treat them.

With regard to the knowledge in each specialty, a late friend of mine who happened to be an ophthalmologist put it this way: "Each specialty expands to cover roughly equal amounts of information."  At the time of his statement - books were the standard and he pointed out that each specialty had 2 - 3 volume sets of several thousand pages.  I haven't seen an information age comparisons - but I think that the concept is a good approximation.

That is not to say that specialists are "better" than primary care physicians.  If anything. primary care physicians and specialists count on the fact that those primary care physicians can manage all of the patients health problems except for the one being addressed by the specialist.  Specialists count on primary care physicians for preoperative physical exams, referrals, and ongoing care after they have completed the consultation. The problem for some is that it sets up specialists and subspecialists as the superstars of medicine.  I am speculating about the problem because I certainly don't see it that way.  There is no doubt that some of these specialists are very highly compensated and I won't argue that is right or wrong.  Personal observation tells me that they work as hard as anyone and really don't have glamorous lifestyles.  Being on call to all of the emergency departments in an area for rare problems is not an easy job.  They are there to solve very specific problems, manage one particular illness, or advise the primary care physician about how they would do it and turn the care back over to them.   

Even with the inefficiencies of the American health care system - I think there is evidence of a reasonable distribution.  The neurosurgeon I referred to sees a catchment area of the entire Midwest.  Anyone with a pituitary tumor has access to his expertise.  The retinal specialists can be found generally in any area where there is a city of 50,000 people.  Since retinal tears/detachments, various retinopathies, and macular degeneration are widespread and in many cases age-related these clinics have a much broader representation and provide good access to large segments of the population.     

Over the years that I have been in practice there have been many primary care initiatives. The first initiative was actually threatening to put specialists out of business.  That turned out just to be a managed care organization (MCO) tactic.  The second wave was forcing MCO primary care physicians to authorize all approvals for specialty care - the so-called primary care gatekeeper approach.  I can't imagine how much time that wasted.  After managed care organizations realized that they could hire specialists and monopolize them - they also realized that they could make money by "managing" them.  That was not 100% effective because now specialists realized they finally had some leverage against managers and could take their business off campus and manage it more effectively themselves.  I have seen many variations of pro-primary care and anti-specialist rhetoric over the years.

The problem is that the money never follows the rhetoric.  Instead of just paying lip service to primary care why not actually pay them for managing multiple morbidities in an aging population? Why not recognize their expertise?  There is no health care company that I am aware of that comes close. MCOs are trying every way possible to reimburse primary care at rates so low - they barely cover the overhead.  Government payers are doing the exact same thing.  The government programs like Medicare are so bad that many primary care MDs are disenrolling and engaging in a cash only practice.

On the academic side, where are the primary care centers of excellence?  Where are the mission statements about managing multimorbidities and being the best possible specialists to do that?  Primary care specialists need to own and promote their expertise, especially how they interface with specialists.

It turns out that there is plenty of room for both primary and specialty care in modern high tech medicine.  Specialization should be remorseless and managing multimorbities is as specialized as laser surgery on a retina.  Once again it appears that the real problems of health care systems are being projected on physicians when they have developed critical treatments that were not around even 20 years ago.

The idea that we should travel back to that point in time - is totally unacceptable to me and the tens of millions of other patients who have benefited from these developments.

George Dawson, MD, DFAPA




References:     

1:  Richard Smith. Doctors and patients heading in opposite directions.  BMJ Opinion. BMJ Feb 1, 2018.  Link.

2: Violan C, Foguet-Boreu Q, Flores-Mateo G, Salisbury C, Blom J, Freitag M,Glynn L, Muth C, Valderas JM. Prevalence, determinants and patterns of multimorbidity in primary care: a systematic review of observational studies. PLoS One. 2014 Jul 21;9(7): e102149. doi: 10.1371/journal.pone.0102149. eCollection 2014. Review. PubMed PMID: 25048354; PubMed Central PMCID: PMC4105594.

The Most Important Decision In Your Life......

See Complete Reference Below

I thought a while about how to write this.   There are a lot of opinions out there about how a decision like this one should be philosophical or religious.  After practicing psychiatry for over 30 years I have to come down on the side of practical.  The most practical decision I think that anybody can make is to stop using intoxicants, at least to the point of intoxication.  I don't really care what your current intoxicant is.  It could be alcohol or cannabis or heroin.  Deciding to stop it will only improve your life and the lives of your family and friends for any number of reasons.  At this point I am a witness to the thousands of people who have stopped and seen those improvements.  I am also a witness to the unfortunate thousands of people who did not stop and ended up dead, incarcerated, homeless, chronically mentally ill, in nursing homes, or leading miserable lives.  I am not naive enough to think that my little argument here is going to make that much of a difference and will elaborate on that in the paragraphs that follow.

One counter issue that I want to address as early as possible because it is often used to short circuit arguments against intoxicants is what I consider an American pro-intoxicants argument.  It certainly can exist in other cultures, but I am restricting my comments to Americans because of the pervasive attitudes about intoxicants.  The most obvious attitude is alcohol and drug use as a rite of passage to adulthood.  This is a well documented phenomenon rationalized at several levels.  Common examples include: "If one is old enough to vote or go to war they are old enough to drink."  There is abundant current evidence that 18-21 year olds if anything are exposing brains that are neurodevelopmentally immature to the effects of alcohol and street drugs - often at toxic levels.  Rational arguments against exposure are not likely to have much of an impact on a population segment in the throes of the invulnerability of youth.  Even apart from the brain based argument, the driving and risk taking behavior of this group is well documented.  Adding intoxicants to the mix is not likely to alter those decisions in a positive way.

An extension of the rite of passage argument is the rights argument as in "Alcohol and tobacco are legal substances and therefore I have a right to use them."  There is no doubt that is true, but the right is limited.  Only people of a certain age can use these compounds and in the case of intoxicants that can affect public safety - their use is even more limited.  People who I have seen invoke the rights argument are generally not talking about limited rights.  The modern version of the rights argument is that "no one should have the right to tell me what I can put in my body.  On that basis all drugs should be legal and easily accessible".  A complementary argument is: "Alcohol and tobacco kill more people every year than (fill in favorite intoxicant here) and therefore I should be able to use it."  Another complementary argument that often gets more support is: "The War on Drugs is a complete failure.  All drugs should be legal and that way we can tax it and make a profit from it.  We can put the cartels out of business."  The rights argument frames an idyllic drug consuming society immune to the medical problems of acute intoxication and addiction as well as all of the associated social and legal problems.  Extreme arguments like this suggest to me that they are driven in part by desperation.  Of course intoxicants need to be regulated - we already have ample evidence of what happens when they are not.  The basic problem that they reinforce their own use at increasing levels cannot be ignored.  Tax on intoxicants is generally an unreliable revenue source when the total cost to the taxpayers for that intoxicant and the fact that revenue is diverted away from covering those costs.
  
A second cultural phenomenon is the use of intoxicants for celebrations.  Weddings, funerals, and various parties often result in the excessive consumption of alcohol. I attended a funeral where the clergyman addressed half of the audience and suggested that an AA meeting might be in order afterwards.  The deceased was probably a victim of excessive alcohol use.  Although alcohol remains predominant in many of these settings, since the 1970s second and third intoxicants are also common.  The relevant consideration is whether these celebrations can occur without the intoxicants.  Interestingly, that decision may come down to the cost of having an "open bar" versus less expensive alcohol on tap. 

A third consideration is the subculture of extreme use.  Many states are notorious for per capita alcohol consumption, binge drinking, and driving after drinking too much.  I don't think that the problem has been well studied, but growing up in a heavy drinking or using culture exposes anyone to early use and reinforcement that are both precursors to problematic use. 

There are several arguments in the popular media that seek to minimize the potential impact of drugs on your life.  Think about the counterarguments:



1.  If I don't have a diagnosis of alcoholism or drug addiction my pattern of using intoxicants is not a problem:

The most absurd presentation of this argument was the idea that a significant number of binge drinkers do not meet diagnostic criteria for alcohol use disorder.  I can't count the number of people who I know that have had their lives ruined or ended by a single drinking binge.  Many high schools in the US started a senior party strategy because so many students were killed around the time of graduation parties due to acute alcohol intoxication.  The drivers in these cases were not alcoholics.  They were high school seniors many of whom had limited exposure to alcohol before the fatal accident.  Binge drinking and acute intoxication is associated with a long line of accidental deaths, alcohol poisoning deaths, suicides, homicides, intimate partner violence, rapes, and other crimes.  All preventable by not binge drinking or more importantly getting intoxicated in the first place.  The same pattern follows every other intoxicant.  If you put yourself in a mentally compromised state in practically any setting - bad things will happen whether you have been diagnosed with a substance use disorder or not.

2.  Alcohol is a heart healthy beverage:

The CDC and the American Heart Association both recommend moderate intakes of alcohol and they define that as one standard drink of alcohol per day for women and one or two standard drinks for men.  This is based on data that shows that these amounts of alcohol may confer reduced risk for heart disease but that higher amounts increase risk.

3.  Intoxicants can be good for your health - some are natural medicines:

The great natural argument leaves a lot to be desired. It's like listening to that guy in a bar tell you that his doctor told him he could drink as much wine as he wanted because it was a natural beverage and then realizing that he is standing in a puddle of his own urine. Peak alcohol consumption in the US occurred at time when it was considered a medication in the early part of the 19th century.  The current best example is cannabis, a substance that has been around for at least 10 centuries and suddenly it is a miracle cure for everything.  The obvious question is why that wasn't noticed in that last 1,000 years. 

4.  Alcohol and drug use disorders are not diseases - it is a question of choice and therefore I have nothing to worry about:

Despite what you may read on some online blog, in opinion polls most people consider alcoholism and addictions to be diseases.  Almost everyone has had some contact with people who have these problems and they see that the usual negative consequences that cause most people to correct their behavior - have no effect on the addicted.  There is no or at least limited capacity for self correction.

5.  I am a libertarian and I believe that all intoxicants and drugs should be legal - I should be the only person deciding what goes into my body:

A familiar argument that ignores human history. The reason that there are controls on addictive drugs is because a significant part of the population will use them in an uncontrolled manner and that generally leads to a chaotic society with all of the costs of that chaos. The more free access there is - the more addiction and chaos.

This argument implies that everyone is the best judge of "what I put in my body" based on political beliefs. There is no evidence that is true.

6.  I am an adult and if I want to have a drink - I will have a drink:

That is a minor variation of the libertarian argument for non-libertarians.  It is basically a truism - yes of course unless you are prohibited by law (and some people are) you can have a drink.  Doing something basically because you can strikes me as a shallow argument. Looking at what happened during Prohibition, I think it is safe to say that the right to drink was preserved by a relatively vocal minority of people who want to drink.  They want to drink for the previously cited cultural reasons and in fact there were some famous exceptions to Prohibition that were based on purported religious ceremony and requirements for alcohol. 

A similar argument is that if a person wants to feel high "there is nothing wrong with that."  At a superficial level and strictly speaking that is true as long as the level of intoxication doesn't lead to medical, safety, or interpersonal problems. The larger question is whether there is something better to do. Let's define better as another recreation that leaves you better off than using intoxicants.  In that case walking around the block is better than getting stoned.

7.  It is part of my creative process:  

There are reviews and books written about how creative people have used drugs and alcohol to enhance their creative process.  These works are by their nature anecdotal.  I am unaware of any controlled sober group and their creative process but it is likely that they exist in large numbers.

8. I am self -medicating and need it to treat insomnia, anxiety, depression, and/or pain:

Self medication implies that intoxicants are actual treatments for these problems. If you talk to any person who uses this strategy - the amount of relief lasts for a few hours.  People tell me: "Look doc - if you can't get rid of this anxiety - I know how to get rid of it for a few hours."  Using alcohol, street drugs, or diverted prescription medications is usually a recipe for worsening symptoms and tolerance.  In that setting people often have the idea that more drugs will bring back the few hours of relief and there are always examples of associated catastrophes in the news. 

9.  The political argument that by allowing universal access to drugs - the cartels will be out out of business - 

Very common to hear that all drugs should be legalized and hear this argument in the next breath.  Most of the people making this argument seem naive to fact that black markets still exist with legal intoxicants.  In the WHO Global status report on alcohol and health 2014, 24.8% of the alcohol consumed was outside of government control.  In the US, it was 0.5 liters of a total of 9.2 liters per capita.  For tobacco the black market is somewhere between 8.5 and 21% of sales. In Colorado there is currently mixed concern about the possibility that drug traffickers are in plain sight, continuing to grow cannabis in remote areas and transport to other states, but reliable information is not available. In the case of heroin, the current impetus for its use is that it is 25% the cost of diverted pharmaceutical opioids.  In the worst case scenario of legalized opioids with no control is it realistic to consider governments regulating heroin at that low cost to consumers?  If not it is a recipe for continued uncontrolled black markets. 

10.  The "You are an prohibitionist" counterargument:

Whenever I present any of my arguments for avoiding intoxicants in the list above, there is the inevitably that some very angry guy accuses me of being a prohibitionist.  I don't know how much weight that ad hominem carries but I always find it amusing. If prohibition worked, I would not need to make these arguments.  My blog is one of the few places where you can see a graphic of how things went during prohibition and it obviously wasn't good.
 
Believe me - you can go through life without ever taking a drink, smoking a joint, snorting cocaine, or injecting heroin and not miss it.  The best case scenario is that it adds nothing to your quality of life.  It is also tempting to think that you have plenty of time to quit later.  With that plan many people either never quit or realize when they are 40 years old that they have been in a fog for 20 years.  Addictions sneak up on you and steal what should be your most productive years.

In fact none of the people with addictions who I talk to ever started out believing that one day they would end up with an alcohol or drug use problem.  Recognizing all of the defective arguments listed above is a good first step.  The most important ability to prevent addictions is self correcting abstinence.  If you wake up one day and realize you dodged a bullet when you were intoxicated, think long and hard about avoiding that situation again.

If you can't - you may have a serious problem.


George Dawson, MD, DFAPA



Supplementary:

Graphic at the top is from:

Lavallee RA, Yi H.  Surveillance Report #92: Apparent per capita alcohol consumption: national, state, and regional trends, 1977-2009.  US Department of Health and Human Services. Public Health Service.  August 2011.  Link.