Showing posts sorted by relevance for query airborne. Sort by date Show all posts
Showing posts sorted by relevance for query airborne. Sort by date Show all posts

Monday, August 17, 2015

Is It Time To Quarantine Air Travelers?



My wife and I just got back from Alaska on August 10, 2015 and within a few days became progressively symptomatic with an influenza-like illness that appears to be peaking today on day 5.  I know exactly how we were infected.  There were several ill passengers, particularly in close proximity who had not mastered coughing into the crook of the arm and who were actually coughing and sneezing over the top of the arm.  The plane was packed as usual.  We had paid an extra $100 to be able to sit in "economy comfort class".  In fairness there was about an extra 4 inches between my knees and the back of the seat in front of me (and I m 5'10'' on a good day).  Even that could not make up for the severe ergonomic problems of airplane seating.  I would quickly describe those as a lack of upright, even in the upright position.  Upright is at least 15-20 degrees from upright and over the course of a 5 hour flight that can create quite a bit of pain in anyone with a back problem.  This problem has been studied to some extent as evidenced by bullet point 3 on this web page.  The economy comfort class also comes with free alcoholic beverages, and I saw one passenger who was clearly uncomfortable rapidly down 4 drinks.  The other ergonomic problem is an ill defined seat.  It felt like sitting on 5 or 6 tennis balls all the way.

But back to the focus on viruses.  From discussing the problem with friends and family it is almost a universal experience that people get viral illnesses on their flight back from a recreational or work destination.

When I boarded a cruise ship recently I was screened for GI symptoms and asked if I had any recent illnesses as part of the check-in procedure.  That did not happen at any point when I got on either of the direct flight to or from Minneapolis.  In addition to the screening procedures there was hand sanitizer being actively and passively dispensed throughout the ship and on the ships TV channel the following message played continuously on a 24/7 basis:

Please wash your hands often and use the sanitizer stations provided throughout the ship especially when you are coming from ashore.  Always use a fresh cup when using beverage dispensers and refrain from using personal containers directly or on common beverage stations.  To stay healthy wash your hands with soap and warm water frequently.

 In comparing respiratory infections from air travel to Norovirus infections on cruise ships there are important differences.  The Norovirus infections occur in a well defined captive population in  very specific time period.  If an outbreak occurs it can become widely known, to the public relations detriment of that cruise line.  If a respiratory virus is contracted on a flight, everyone leaves the plane after arrival in a few hours and the total number of people infected is unknown.  There have been studies that look at the attack rates of people who have been on a flight where there is an index case of influenza and also the effects of using masks prophylactically when there are known index cases onboard.  There are no cautions to the passengers about how to prevent the spread of respiratory infections and (to my knowledge) no easy way for them to cancel in the event that they develop an acute upper respiratory in infection.  The CDC has some limited guidance on air travel, including some information on influenza transmission cabin air conditioning including the fact that it is partially recirculated and HEPA filtered 15-20 times per hour.  The most interesting study in microbial diversity in commercial aircraft that I could find was by Osman, et al (1) who compared conventional culture techniques to available molecular probes in 2008 in samples from 16 domestic and international flights.  They conclude that the molecular probe techniques demonstrated a much greater microbial diversity than culture techniques and that microbes varied significantly from domestic to international flights.  The molecular probe techniques identified 12 classes and 100 species of bacteria in cabin air, but in sufficiently low concentrations to not present a health hazard.  I am aware of studies in the past that have done viral cultures for respiratory viruses on filters in buildings but could not find similar data for commercial aircraft.  There have already been simulations about what happens when a person sneezes on an commercial aircraft, and those results are eye-opening.  I posted that in a look at the issue of hand washing and respiratory viruses.

Rather than go into excessive detail about the limited research that has been done so far, let me summarize a few facts and my conclusions.  Respiratory viruses can be transmitted during commercial air travel.  The attack rate for influenza virus has been estimated to be 2 - 4%.  There has been at least one study that shows masks can prevent infection.  There have been several simulations of how air travel potentially increases the world wide spread of airborne viral infections and some of these infections like corona virus and SARS outbreaks puts a significant burden on the international public health community.  Furthermore, the public health burden in terms of both morbidity and mortality is huge.  Influenza virus alone kills about 20,000 people annually in the United States or the equivalent of 5 large cruise ships in terms of total lives.  By comparison, there if far more press coverage of a Norovirus outbreak on a cruise ship and that virus is much less fatal.  Every American contracts about 2 - 3 respiratory viruses per year of varying severity.  That probably amounts to about 2-6 weeks of illness per year, associated with a disruption of work and daily activities as well as increased infection risk for those in the sphere of that person's routine.  There is also a risk for exacerbation of chronic illnesses like asthma and chronic obstructive pulmonary disease.

All of these considerations lead me to suggest (at the minimum) - the following measures:

1.  Intensification of study of airborne diseases especially respiratory viruses:  The technology is certainly there and there is no reason that molecular technologies cannot be applied to samples from commercial aircraft and I think that the HEPA filters are a logical place to start.  I would really like to see this become a focus of a private research fund, because it seems like the federal government has created numerous monitoring systems but no practical ways to detect high risk scenarios and disrupt disease transmission.  It seems like that is likely to occur only after an outbreak of a highly fatal respiratory virus occurs.

2.  Passenger education is critical:  The airline industry needs to adopt the methodologies that are currently employed in the cruise industry - educating everyone on the plane, screening for passengers at risk and quarantining them if necessary.  A critical piece of the education process is that while hand washing is necessary, it is not sufficient to prevent the spread of airborne respiratory viruses.  That public needs more awareness of that concept and what else can be done.  The method of quarantine is debatable and would probably need some flexibility based on passenger needs and acceptability and the severity of the problem.  It could include grounding until the infection clears, use of masks to block airborne infection, or possibly a section of the passenger cabin with more intensive HEPA filtering (altering air flow and humidity can affect the likelihood of virus transmission).

3.  Developing a culture to reduce the risk of respiratory virus infection:  Everywhere that I look we have practices in place that encourage the transmission of respiratory viruses.  Most Americans do not let respiratory viruses stop them from carrying on their business as usual.  In the past few days, I have personally walked through clouds of sneezed droplets because I happened to be following a fellow customer or coworker too closely at the wrong time.  I can't recall exactly when it happened, but getting rid of sick and vacation time and replacing it with paid time off or PTO days is an incentive for going to work sick.  Most of that sickness is respiratory viruses.

The American attitude to the common cold is far too casual.  It does not take into account the spectrum of symptom severity and the fact that many of these viruses can cause influenza-like illnesses and very severe syndromes.  Even a cold of moderate severity generally curtails a lot of activities and produces significant morbidity.  I don't understand how the medical and consumer community has come to this level of acceptance and denial of this collection of more-than-just-a-nuisance pathogens, but I would like to see it stop.

The American attitude toward the bad ergonomics of airline seating is another issue.  I think it is unfortunate that most passengers these days have never flown on a 747.  I may be overidealizing the flying of my youth, but planes today seem like dismal narrow aluminum tubes by comparison.



George Dawson, MD, DFAPA



References:

1: Osman S, La Duc MT, Dekas A, Newcombe D, Venkateswaran K. Microbial burden and diversity of commercial airline cabin air during short and long durations of travel. ISME J. 2008 May;2(5):482-97. doi: 10.1038/ismej.2008.11. Epub 2008 Feb 7. PubMed PMID: 18256704.

Supplementary 1:

For a graph of the URI I contracted on the Alaska vacation and most likely on the flight home follow this link.


Attribution:

The graphic at the top of the blog is directly from the CDC and one of their pages on Middle East Respiratory Virus Coronavirus.  Photographic credit is given to Jennifer L. Harcourt.  The picture depicts coronavirus particles in the cytoplasm of an infected cell.

Friday, February 7, 2014

Medical Knowledge Goes A Long Way - Or Does it?

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

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

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

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

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

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

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

            

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

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

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

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

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

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

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

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

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

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

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

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

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

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

It must be mind boggling.

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

That is true for doctors of all specialties.

George Dawson, MD, DFAPA

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

























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



Monday, January 17, 2022

This Is How Civilization Ends...

I had that thought immediately after seeing the above graph on the CDC web site. Over a million new cases.  An all-time high by far.  At that point, the news had been heavy with discussions about the Omicron virus for about 3 weeks. The trail though Africa and Europe was described.  In the United States we had plenty of warning and plenty of time to adjust.  It wasn’t like that first peak in the fall and winter of 2020-2021.  Back then there were no vaccinations.  My wife an I finally got vaccinated in March of 2021 and then only by an extraordinary stroke of luck.  Before Omicron we were flush with vaccinations.  Two different retail pharmacy chains were scheduling appointments and they were free. When the booster came out that was also free and much easier to get. The overwhelming scientific evidence was that the immunizations were safe and effective.

The public health measures seemed less effective. That could be confirmed by a walk around Target or Walmart. At the absolute peak of mask wearing in Minnesota, my estimates were up to 30% of shoppers were masked. Half of those masks were loose fitting cloth masks and probably not very effective. Today, at the height of the Omicron spike 10% of the people in my coffee shop were masked and I was the only guy wearing an N95.  Despite an increasingly vocal group of aerosol scientists most people remain shockingly ignorant or willfully ignoring the airborne route of transmission. The most easily observed scenario is restaurant dining where the customers wear a mask to the table and then take it off to eat and talk for the next two hours. There is no magical protection from airborne virus in that scenario. Forget about the 6 feet safe distance rule at the start of the pandemic. Looking for restaurants that have improved their HVAC systems to improve airflow and air exchanges over time was also disappointing. So far in the Twin Cities Metro area I have found 1 restaurant. No restaurant or business as far as I know is posting their air exchanges per hour or carbon dioxide measurements to describe the potential risk of their environment. They are posting that they adhere to social distancing and all of the surfaces are wiped clean between diners.

Despite all of that inertia, the restaurants are packed.  Typically, shutdown occurs when a significant number of staff are ill with coronavirus and they cannot stay open. I dodged a bullet at Christmas just as infections were increasing. My wife and I were supposed to meet another couple at a restaurant. My suggestion to get take out and eat it at either of our homes was met with resistance. I was saved by a call from that restaurant that significant numbers of their staff were ill and they would be closing until things improved.   

The general cultural landscape has been even more grim. I follow all of the experts in the media on a regular basis – Drs. Fauci, Hotez, Jha, and Walensky.  On an average day they are awash in a sea of misinformation.  That sea contains the entrepreneurs who see the pandemic as a money-making scheme as well as the purely irrational who find that conspiracy theories about the virus, vaccine, and public health measures are easier to understand and believe than the science. Political opportunists are in the mix and as recently as today were suggesting that “white people” were being discriminated against and were less likely to get the vaccine as a result. The Florida Governor made this statement:

“We reject the biomedical security state that curtails liberty, ruins livelihoods and divides society.”

Biomedical security state? The politicization of this pandemic knows no bounds. It obscures both the science and goodwill toward the scientific and medical communities.  But it doesn’t stop there.  In some large health care organizations 10% of the workforce has been fired for not complying with workplace mandates on COVID-19 immunizations.  Some of these workers are physicians who should have been taught basic epidemiological concepts – the most basic being that vaccinations are a rare medical miracle that have saved the lives of tens of millions of people.  Disease have been eradicated, prevented, and the course of infectious diseases has been altered.  And even if you are not a physician, everyone has the experience of taking all of the mandatory vaccinations required to attend school.  Most of these vaccinations had a significantly worse side effect profile than the currently available COVID-19 vaccinations.

Apart from reducing rates of infection, hospitalization, and death these modern vaccinations also reduce the risk of chronicity. Chronic or “long COVID” symptoms might occur in as many as 70% of patients after the infection. Remission rates and rates of disability are still being determined at this time.  Given the risk/benefit considerations of the vaccinations it is difficult to see how any rational person would refuse it.  It is even more difficult to understand how a rational person would not take basic measures to protect themselves and their families from airborne virus or justify ignoring the pandemic on the basis of a completely implausible conspiracy theory. In some cases, the motivations are very clear.  Politicians would rather use various forms of rhetoric to attack the idea of a pandemic and what it takes to resolve it for political gain rather than taking positive steps recommended by experts. It is a standard political tactic.  That rhetoric has been advanced to extreme levels and to the point where scientists and their families are being threatened.  Today the suggestion that “white people” were being discriminated against struck me as white nationalist rhetoric.  It was viewed just as another “falsehood” in the media.  Certainly, blind partisan acceptance of these statements is not very likely to exhibit flexibility in thinking about the pandemic, the virus, or possible solutions.

The press has stepped in and commented on the process as a “mass delusion” or “mass psychosis” as if the use of psychiatric jargon by a journalist would add credibility to the criticism of many people thinking and acting irrationally. Many of them are agitated, visibly angry, and can become aggressive typically when confronted about pandemic precautions in schools and businesses.  Hardly a day goes by without seeing an airline passenger or town hall meeting participant screaming until they are red in the face and carted away by security. None of these people has a psychiatric disorder.  They can cool off somewhere, suppress their irrational thoughts and the associated anger, and get up and go to work the next morning.  During the run up to the 2020 Presidential election there was heated commentary about President Trump’s mental health and fitness for office. There was some debate in the psychiatric community if it was appropriate to discuss that issue based on Trump’s observed behavior rather than a psychiatric assessment. This essay looks at the other side of that debate. Why do so many people follow leaders who make repeatedly false statements that in some cases are viewed as potentially inciting people to do the wrong thing? And conversely – how do so many people accept the more obvious rational path and reject all of the paranoia and conspiracy theories?

There are of course numerous theories about how this comes about.  The theories generally depend on the same theories that have been used to describe normal development, psychopathology, and normal learning processes.  In some cases the theories have a philosophical basis – that seem to be fashionable these days. And despite many of these theorists incorporating a neurobiological model – very little explanation about how that is relevant.

The relevance is obvious to me starting with the relationship between emotion and cognition specifically decision making. In order for it to be obvious, the relationship between emotions and normal decision making needs a brief exploration. Human decision making typically occurs as an integrated process in the frontal cortex. I won’t digress into any subdivisions or tracks in this post. The key word here is integrated. That means the frontal cortex takes a large number of inputs and uses them to varying degrees in the ultimate decision. That includes a lot of memory input, specific types or learning, emotional input, and real time sensory and perceptual data.  The amount of input is large and much of it occurs at an unconscious level. How it occurs is largely unknown at this point but with our limiting inputs have been determined.  One of those inputs is emotion. We know for example from lesion studies that emotional input is absolutely critical for normal day to day decision making. Of the vast number of potential decisions we all have a subset that are associated with emotional valences that can affect our preferences. Without access to those valences decision making slows and grinds to a halt.

Restricting our consideration of the decision space to all of the possible decisions about the pandemic and how to proceed – all of the medical, scientific, personal, political, manipulative, and conspiracy theories the possibilities are very large. If we have 300 million decision makers and they all have unique conscious states and personal capacities for decision making the potential outcomes are large. It is also a more complex scenario than all of the typical explanations for pandemic denial.  Each one of our 300 million decision makers has unique experience affecting the emotional valences of their decisions. The overt decisions may seem to coalesce at some points but for many different reasons. For example, believing what a politician says despite the clear documentation that they are lying can occur as the result of identification with similar people in the past, identification with a general class attitude or ethos that it represents, or it simply could be activated by the angry emotion that politician effects. Those are just a few possibilities.

The pandemic vaccination vs. anti-pandemic antivaxx is by definition a binary polarized debate – the reality based on what we know about how the brain works it is far from that simple.  Even on what appears to be the rational side there is no Spock-like analysis.  The public health experts are all accessing emotion when making their decisions. Rational thought is reward-based learning and associated to one degree or another with a “Eureka” moment.    

The key question going forward is what can be done to address the degrees of freedom associated with the possible decisions of this brain process.  What can be done to improve the process and by improve, I mean assure that civilization survives the current and potentially more lethal pandemics. To that end, there are numerous cinematic depictions of apocalyptic pandemics. Based on the depictions prior to this pandemic they are probably fairly accurate. Once a lethal pandemic takes hold, the decision space for survival collapses as fewer and fewer decisions are possible. An intuitive writer or film maker knows that at some level.  Time to make it general knowledge.

 

George Dawson, MD, DFAPA

Sunday, April 5, 2020

Acute-Care Psychiatry During the Pandemic




in the early days of this century, I spent a lot of time in Avian Influenza Task Force meetings. I was on two separate task forces and at the same time working on an acute care inpatient psychiatric unit. One of the meetings took up four hours in the afternoon and I would have to go back to my unit and make up those four hours. I made the mistake of that not saving all the documentation from those meetings. There were hundreds of pages. The main focus of one task force was on “surge suppression” or helping with crowd control to prevent emergency departments from being overwhelmed by people who did not really have the viral infection. The other meeting was more about the actual response to the viral infection. I was always skeptical of what I heard. We kept hearing that if there was an epicenter of infection, large pallets of Tamiflu would be on the way. We saw presentations with pictures of those pallets under plastic wrap. At the same time there was discussion about morgues and refrigerated trucks that have become part of the current crisis.

I was more concerned about what would happen to inpatient psychiatry units. I kept hearing that the medical and surgical beds would be overwhelmed. When I suggested that we increase the capacity of negative airflow rooms and rooms vented directly to outside air, I was told that was impossible. One expert gave the opinion that if there is an airborne virus in the hospital: “The minute you walk into the hospital you should be wearing an N95 mask”.

That was about 2005 and I had never heard of an N95 mask before that. I had certainly worn masks for painting, dust protection, and various chemical and biological experiments that I did in the course of education and research. I went out and bought a small package of N95 masks. I fitted them per the instructions and noticed a couple of things. The fit was extremely snug due to upper and lower elastic bands (that have a much smaller circumference than a human head or neck), the circular contour of the mask providing a suction fit to some extent, and a flexible metal band that bends over the bridge of the nose to effectively seal that area. When you are wearing an N95 mask your voice is muted and you are breathing against resistance. If you wear it long enough, it becomes soaked with exhaled droplets. I rapidly concluded that it would be nearly impossible to conduct a psychiatric interview wearing this mask.

I never really learned at the time whether there was a plan to shut down inpatient psychiatry and use all the beds for avian influenza patients. Thankfully it never got to that point. Flashing forward 15 years a real pandemic is upon us and the problems remain unsolved. Inpatient psychiatric units and residential drug and alcohol treatment units are considered necessary services in most states and they remain open. Very recent information from the authorities now suggest that SARS-CoV-2, the virus causing COVID-19 is airborne and that there are a significant number of asymptomatic carriers.

I have been using telepsychiatry at this point for two weeks and it seems to be going well. There are definite constraints compared with face-to-face interviews. I have noticed more constraints since my original post on this topic. I put a couple of questions out there on social media today to see how my colleagues who are still actively engaged in acute care are adapting to the changing parameters of this pandemic. Before putting those questions out, I had the thought that telepsychiatry could be used over the short distances in inpatient settings. As a resident I had the experience of observing psychotherapy firsthand and being observed from adjacent rooms that also had microphones for communication between those rooms. I was interested in seeing whether or not anyone had implemented those solutions.  I was pleased with the feedback that I have so far.

One of the first responses was that psychiatric staff were using surgical facemasks and face shields in some settings. In other settings, adjacent rooms and telepsychiatry both on-site and off-site were being used for acute-care units. The most unique solution I heard of was a consultation liaison team using iPads to interview medical and surgical patients remotely where possible. That reminded me that some people have joined my telepsychiatry sessions using smart phone apps. It was generally very suboptimal if the phone was not completely stabilized.  I also had the experience this week of getting a link sent to me from a colleague who worked for a large healthcare system. It was an invitation to open up a video session with him even though I am not registered in his clinic.  It was very similar to a Zoom session that I did for a podcast. All this information shows that there are technologies available right now that are effective and actively being used. They have also been very rapidly deployed or are in the process of being deployed. There is some potential that this sudden change in the delivery of psychiatric services may be a more permanent one.

I asked the question about whether or not the services were saving personal protective equipment (PPE). The response to that question was somewhat mixed. I am not clear on what it means but speculate that some of the staff still need to have direct patient contact at some point during the day. Most acute-care staff at this point have been assigned PPE. The PPE specifics seem to vary from place to place but it is clearly rationed. If I was designing a survey of acute-care psychiatric facilities I would like to see the specifics of how many people had N95 masks and other kinds of protective gear.

Preadmission screening remains a question mark.  There is general agreement that there is an asymptomatic carrier state for SARS-CoV-2 (1,2).  Carriers may have a lower viral load and be partially symptomatic. Most people admitted to inpatient psychiatric units these days require intensive nursing care for their own safety. If there were environments where patients with COVID-19 could be safely segregated and treated that would be ideal, but I doubt those kinds of environments exist on inpatient psychiatric units. Even then the asymptomatic carriers would require the same psychosocial interventions as non-carriers.  The general screening done is to ask about contact with known cases and daily temperatures. I am not aware of any screening procedures that involve trying to identify the virus and carrier state.

My overriding concern is that medical and psychiatric staff everywhere have adequate protection. We have known since my days on the avian influenza task forces that airborne viruses are difficult to contain. They can infect through surface contamination, droplet contamination, and traveling on air currents. Working to cancel all those routes of infection is a tall order especially on an inpatient psychiatric unit.

The only practical way to maintain the level of communication necessary and minimize risk of infection is through some type of electronic communication. Some of the early methods have been listed in this post. Having worked in these settings for a large part of my adult life I am very concerned about the staff with daily direct patient contact including nursing, nursing assistants, and occupational therapy.  Housekeeping staff also have a vital role and are directly exposed to most contaminated surfaces. I have seen large numbers of inpatient staff come down with seasonal respiratory viruses and I know that vulnerability is there. They all need PPE. We need additional innovation in these settings to protect all staff and patients.  

And we have needed that innovation for a long time.


George Dawson, MD, DFAPA




References:


1: Lai CC, Liu YH, Wang CY, Wang YH, Hsueh SC, Yen MY, Ko WC, Hsueh PR. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect. 2020 Mar 4. pii: S1684-1182(20)30040-2. doi: 10.1016/j.jmii.2020.02.012. [Epub ahead of print] Review. PubMed PMID: 32173241.

2: 1: Hu Z, Song C, Xu C, Jin G, Chen Y, Xu X, Ma H, Chen W, Lin Y, Zheng Y, Wang J,Hu Z, Yi Y, Shen H. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020 Mar 4. doi: 10.1007/s11427-020-1661-4. [Epub ahead of print] PubMed PMID: 32146694.

Supplementary 1:

I am very interested in what you are doing at your facility to contain this virus while continuing to go to work every day and treat patients.  I am also very interested in whether you have enough PPE.  I am interested in hearing from everybody staff psychiatrists, residents, social workers, occupational therapists, nurses, nursing assistants, and housekeeping staff.  Please post in the comments section below and feel free to remain anonymous. 


Graphic Credit:

Shutterstock per their standard agreement.






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.

Monday, August 5, 2013

Asthma Endophenotypes? Their Implications for Psychiatry

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

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

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

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

2.  Objective assessment as evidenced by:

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

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

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

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

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

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

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

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

George Dawson, MD, DFAPA




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

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

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

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

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

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

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



Monday, March 16, 2020

The First Case Report - Implications For Coronavirus Conspiracy Theories



At the time of this writing I have encountered at least three coronavirus conspiracy theories.  The American version goes something like this. The current pandemic resulted from a leak from a Chinese bioweapons laboratory. The supplementary information generally talks about how these particular bioweapons labs are not very secure and leaks are common. The Chinese version has a human twist and it involves a visit to China by 300 US military athletes. The suggestion is that these athletes intentionally introduced the virus or inadvertently passed the virus to the Chinese population. There is an Iranian version - suggesting that the virus is basically an American bioweapon.  There are various embellishments. Prominent politicians are involved in restating these conspiracy theories. I have been reading about bioterrorism for the past 20 years and would dismiss these theories as being implausible from a technical perspective. From a political perspective, it makes perfect sense to me that politicians will always try to look for a way to deflect any responsibility. One of the most common ways to do that is to blame an adversary - especially one that might be unpopular with the majority of citizens.

The report of the first case of coronavirus in the US is a rare opportunity to end all the conspiracy theories with real evidence. I do realize that conspiracy theories are not generally refutable by facts.  This post is directed at those who can incorporate factual information into their worldview. There has been a lot written lately about distinguishing opinion from fact, including the results of a standardized international test suggesting that American students may have some deficits in this area.

Detailed case report in the New England Journal of Medicine is interesting from a number of perspectives.  The patient is a 35-year-old man walked into an urgent care in Snohomish County, Washington on January 19, 2020 the four-day history of cough and “objective fever”. He had returned from visiting relatives in Wuhan, China. His health history was basically unremarkable. Initial vital signs showed a temp of 37.2°C, BP of 134/87, and pulse was 110 bpm. Restaurant rate was 16 breaths per minute and O2 sat was 96% on room air.  Initial viral screen for influenza a and B, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, and for common coronaviruses was negative. The CDC was contacted and samples were collected for 2019-nCoV. The virus was confirmed one day later.

The patient had been discharged home but after 2019-nCoV was confirmed he was admitted to an airborne isolation unit for observation. The clinical course is described in the figure below that is taken from the original paper (with permission). The symptom course before the admission date of January 20 is estimated on the diagram. I think it is instructive to note that cough preceded the development of a low-grade fever on day five of 37.9°C or 100.2°F. The patient also had fatigue nausea and vomiting before the development of fever.



Laboratory findings over the course of the illness are presented in the original article and six blood samples did not show any marked abnormalities. He had mild elevations of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Blood tests were done due to fevers and they showed no growth.  Chest x-ray on day 9 of the illness showed left lower lobe pneumonia that correlated with decreased O2 sat down to 90%. At that time he was put on supplemental oxygen. It is also treated with vancomycin and cefepime for presumed hospital acquired pneumonia. On day 10, based on his chest x-ray, the need for supplemental oxygen, and reports of the development of severe pneumonia is physicians decided to treat him with an investigational drug - remdesivir. By day 12 he was clinically improved and no longer needed supplemental oxygen. His oxygen saturations were normal on room air. As seen in the diagram, is always symptoms at the time were a cough and rhinorrhea.

Contrary to the conspiracy theories, this paper points out that the Chinese researchers shared the full genetic sequence of the 2019-nCoV in the National Institutes of Health GenBank Database and the Global Initiative on Sharing All Influenza Data (GISAID) database. 

The authors emphasize at the time of this writing that the full spectrum of clinical disease is undetermined. Transmission dynamics are also undetermined because the patient had not visited the seafood market in Wuhan or had any contacts with known cases in China. They list several complications noted in the Chinese population including acute respiratory distress syndrome, severe pneumonia, respiratory failure, and cardiac injury. There are several radiographs on Twitter suggestive of significant lung injury and at least one report of myocarditis in a significant subset of patients. The authors also point out that the patient is nonspecific symptoms prior to the onset of pneumonia were consistent with the number of common respiratory viruses. In differentiating this illness travel history, the decision by the patient to seek treatment, and a coordinated effort among public health officials led to the timely identification of the virus. I would add that this case report also shows the clear need for clinical expertise as the illness transforms from what appears to be a typical respiratory virus to pneumonia. The question that needs to be asked is whether that level of expertise is available everywhere in the country.

Addressing the threat of emerging infectious diseases requires a public health infrastructure and cooperation across many countries with their own political interests. Many those countries may have public health officials that are cooperating with one another, but politicians who may decide to use a pandemic for their own interests. With most countries engaged in significant quarantine efforts at this time, clear cooperation among world leaders in stopping this pandemic is urgently needed.

George Dawson, MD, DFAPA



References:

1: Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31. PubMed PMID: 32004427.



Permission:

Figure 2 above is from the original article in reference 1 - with permission from the Massachusetts Medical Society.  License date is March 16, 2020 - license number is 4791120888948 for 12 months from the date of the license.