Saturday, February 22, 2020

The Best Advice I Got In Medical School







It has been a long time but when you get to be an old man you can obsess about what you currently know, what you used to know, and how you got here.  I got some life-changing advice as an undergrad but not much good advice in medical school or residency. I can say without a doubt, the best advice I got was:

“If you are sure you are going into psychiatry, take as many medical electives as you can. Don’t take any psychiatry electives because you will be doing that for the rest of your life.”

I did not have to think too much about it because I enjoyed most aspects of medical education and training. The only two negative rotations I had in my training were based primarily on the staffing patterns at the time and they were not major medical or surgical rotations. They also did not seem to be very interesting. Practically all of the medical and surgical residents I worked with were outstanding in many ways. I felt like an integral part of the team and I was happy to do the necessary work.

As a result of the advice I took endocrinology, cardiology, renal medicine, allergy and immunology, neurology, infectious disease, and neurosurgery in addition to the required general medicine rotations. I took a little flak from the Dean. There was some concern that there were not that many spaces available in medical electives. At one point it was suggested that I should limit myself to two or three medical electives. I prevailed and got what I wanted largely because the specific rotations were at a public hospital and the local VA hospital. 

One of the aspects of medical training that is not discussed enough is camaraderie. When you are a medical student, your role is often ill-defined. The role generally depends on the staff you are working with, the institution, and the general culture within the medical school. At the hospitals where I spent most of my time medical students were an integral part of the team. On day one – you are assigned patients and admissions. You were expected to report on patient progress and write progress notes. You learn communicate with everybody in the hierarchy ranging from the intern to the resident to the attending physician. You are supposed to learn how to research and study the specific problems that your patients had and in some cases do a special report. Examples would include a chart review I did on gram-negative meningitis at the VA medical center and presentation on anaphylaxis on my allergy rotation at Milwaukee County Hospital. Both of those studies went extremely well.

But camaraderie is more than knowing the chain of command, hospital systems, and how to get the work done. A key component is the educational quest that everyone is on. Doing rounds with five or six different people at all levels of training ranging from novice to world expert is experience that you don’t get in many places. Some of the results can be stunning. I did a consult on a patient with possible spontaneous bacterial peritonitis (SBP). I wrote up the consult form and prepared to present to the attending physician that afternoon. When he walked in the room from about 10 feet away, he asked everyone else on the team what the problem was with the patient’s leg. I had been focused on abdominal, systemic, and laboratory findings. Nobody could answer the question. The attending physician who happened to be an expert in streptococcal infections, pointed to a rosy rash on the patient’s left shin and suggested that it was a form of streptococcal cellulitis. He did the necessary tests to confirm that diagnosis at his lab.  One of the many processes that must be attended to in these rounds is the pattern matching aspects of diagnosis. It was vaguely implicit in my training and I realized only later when teaching a course in avoiding diagnostic errors - that these rounds are the place to ask experts: “What are you seeing that nobody else is?” All experts including psychiatrists recognize certain patterns and can make more rapid and more accurate diagnoses than people outside their specialty.

A lot of people reading this may have a hard time believing that what you learned in medical school is relevant to a specialty that you practice your entire life. After all - aren’t these specialties updated at some point and doesn’t your knowledge base become dated? It is surprising how the basic approach to the patient that is unique to each specialty does not change much. There is still relevant review of systems, specialty specific diagnoses, and laboratory testing. Working with specialists for even a month gives medical students and residents a clear idea of how to approach patient problems in a systematic manner. Even though there have been radical changes in some specialties like cardiology, most medical specialties change slowly at the mechanistic level typically with some pharmacological innovation. A clear example relevant to psychiatrists is the endocrinology of metabolic syndrome and diabetes mellitus. Over the course of my career that has resulted in increasingly complex pharmacotherapy ranging from insulin, metformin, and sulfonylureas to an additional five classes of drugs and more complicated insulin preparations.

A unifying concept that I learned on all those medicine specialty rotations is that it is important to still know about these mechanisms and medications even if your specialty involves another bodily system and you are prescribing an additional treatment. No matter what specialty service I was on there was never the idea that we could focus only on a specific bodily system and ignore the rest. On all of those rotations including neurosurgery, I was often the person focused on what was going on with the patient’s brain.

Learning medicine and neurosurgery on all of these rotations was quite exciting. I am much more likely to retain information if I am excited about it. I was excited right up until 11 PM on the last day of medical school.  I was doing renal medicine at the time and the senior resident was going to be a rheumatology fellow. We finished rounding about 6 PM and he noticed we had 4 or 5 additional consults. He was the kind of guy that you really like working with. He had a great sense of humor and was always engaging. He could even engage an introvert like me. I remember him saying: “Look I know - this is your last day but you could really help us out by doing some of these these consults. The new team is coming in tomorrow and I don’t want to leave all of these consults behind.” He threw in a couple of politically incorrect jokes for good measure and I headed off to do two consults. We came back and met with the attending physician who was considerably older than I am right now and finished them all by 11 PM. I really did not want to say goodbye to that team. But I headed off by foot across the golf course sized county hospital grounds to my apartment on 89th St.

The knowledge gained in that fourth year of medical school was a springboard for the next 30 years. I continue to read about all those medical specialties and remember what happened in 1982. I continue to research all the medical problems and medicines that my patients are taking. I continue to wish at times that I was still on that renal medicine team back at Milwaukee County Hospital.

I didn’t get a lot of good advice in medical school but for all those reasons the advice about what to do in my fourth year was the best.


George Dawson, MD, DFAPA





Supplementary 1:

Second best piece of advice in med school was from the head of our Biochemistry class in the first year.  Our biochemistry class consisted of lectures and research seminars where we read and critiqued biochemistry research. At one of the first lectures, the department head stated:

"Subscribe to the New England Journal of Medicine and read it."

I have been reading it ever since and that was definitely a good idea.


Supplementary 2:

I did take one psychiatry elective in the last two years of med school - Infant Development and Psychotherapy.  It was taught by two psychiatrists who were very excited about the field Frank Johnson, MD and Jerry Dowling, MD - both Medical College of Wisconsin psychiatrists. We screened infants and very young children at risk especially if they had one or both parents with severe mental illness. We instructed parents on how to interact with their children in order to overcome behavioral difficulties associated with disruption of the infant or child and parental bond.  Every week we had a research seminar where we read relevant papers on the subject.  We had a very large clinic where we did evaluations and saw large groups of parents. It was a very positive experience and has implications to this day.  As far as I know there are no clinics in the US like the one we had in 1982.  It provided a valuable service to infants, young children, and their families.

1: Wesner D, Dowling J, Johnson F. What is maternal-infant intervention? The role of infant psychotherapy. Psychiatry. 1982 Nov;45(4):307-15. PubMed PMID: 7146225.







Sunday, February 16, 2020

Medication Checklist-Current Version





I have posted past medication checklists on this blog in the link below will take you to the current version. I developed this over the last 10 years seeing outpatients who have been treated with various psychiatric medications over the previous 5 to 50 years. During a comprehensive evaluation a history of past psychiatric treatment including hospitalizations, past medications, past psychotherapy, and other biological therapies needs to be discussed. Ideally a patient will recall ineffective therapy from the past that can just be restarted. In my current practice setting that is relatively rare. People with chronic mood disorders, anxiety disorders, and insomnia ever happened men treated with multiple psychotherapies and medications. They are typically seeing me because those past therapies have not worked. It is up to me to come up with a newer and safe approach based on my past history.

There are varied responses to the question about what medications have been prescribed in the past. If it has been a long time since the last episode of treatment many people say they can’t recall the name of the medication at all. In some cases people admit that they never really studied the name of the medication, they just took it out of the bottle at the correct time. There are some people who will get a month-long prescription from a physician and never take a single pill. When people have been treated with multiple medications the responses are more varied like “I have taken all of them”, “I have taken all of the SSRIs”, or “I’ve taken all the SSRIs and SNRIs”. Closer examination often shows that many people take anywhere from 3 to 5 antidepressants over any 20-year span. There are people have taken the same antidepressant for 20 or 30 years and wanted it to be changed.

There are many other questions pertaining to best use of medications including diagnostic clarifications. The commonest problem I see is people misdiagnosed as having bipolar disorder and then not treated in a standard way for bipolar disorder. There are also people who have bipolar disorder who do not receive standard treatment. In this era of direct to consumer advertising, many people are treated with aripiprazole or brexpiprazole who would not have been treated with dopamine receptor blocking agents in the past. That opens up an entire new category of potential side effects and comorbidities.

All these reasons make the history of medication use extremely useful in a psychiatric evaluation.  Formal versions of medication history such as the Antidepressant History Treatment Form (ATHF) have been used in research for 20 years as a standard way to document whether or not a patient has received an adequate trial of an antidepressant (dose x duration). This form generally requires collecting a lot of collateral information especially with regard to the dose. Checklist approach I am using is focused on getting the general name and class of the medication. If I think additional information is required I will try to get the necessary collateral information. But generally I am looking for class effects, especially if it is apparent that the patient cannot tolerate a particular group of medications.

Over the years I have been using it this form has been useful. It is essentially like the memory testing paradigm where you proceed from spontaneous recall to categorical recall to list prompts. This is definitely a list prompt but for much larger universe. That is often why I direct people to focus on a particular section of the list. As an example if I am seeing a young person and they have only taken one or two antidepressants and cannot recall the names, I advise them that they can probably find it in the top half of the antidepressant column. The clinical problem can be managed to subsections of the list.

A disclaimer is in order. This list is for the purpose of discussion among clinicians and possible scientific use. It is not been validated from a psychometric perspective. It is not commercial or for-profit like everything else on this blog. There is no guarantee that it will cue accurate memories of past medications. Like everything in clinical psychiatry, collateral information-in this case from pharmacies is the gold standard. Apart from its clinical use, this list can also function to illustrate the universe of medications that are applied to psychiatric disorders. There can be useful for trainees and since this list is updated, anyone who wants to take a look at current FDA approved medications. The list is generally compiled for convenience. I wanted all the medications to be listed on a single sheet - front and back. I wanted the list to be easily readable even by geriatric patients. I wanted the list to be disposable - in many cases the patient wants to take it with them in order to do future research.

That brings me to the topic of research. Most medical centers have been are large electronic health records for about 20 years at this point. Those EHRs vary significantly in their research capabilities. The obvious study of a list like this would be to see how accurate patients can recall their medication history spontaneously and with this list or a something similar. Optimal membership on the form can also be debated. I eliminated tiagabine from the anticonvulsant section as a misadventure in the treatment of anxiety from about 20 years ago. I did that in order to make room for beta-blockers and orexin antagonists. A colleague pointed out that I don’t have the old amitriptyline-chlordiazepoxide or amitriptyline-perphenazine combination medications. I started practicing over 35 years ago it was extremely common to see those medications being prescribed and thankfully that does not happen anymore. Some of the older medications on the list are of historical interest but also because older patients may have taken them.

The list can be downloaded from the link below. Let me know what you think in the comments section. Please restrict those comments to the utility of this list.

George Dawson, MD, DFAPA


References:

1: Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62 Suppl 16:10-7. Review. PubMed PMID: 11480879. Full Text


Medication Checklist:

Download




Monday, February 3, 2020

Adventures In Vaccine Reactions



This area of erythema appeared on day 3 - only on the arm where the Pneumovax was placed




This post is about vaccinations for old people.  It is a mix of science and anecdotes because that is all there is out there right now. A lot of the information I elicited by posting my experience getting the Shingrix Zoster Vaccine and the Pneumovax 23 Vaccine. It illustrates the concept of biological heterogeneity that I post about on this blog. Many people can seem confused about that, particularly the idea that practically every biological system in the human body has significant heterogeneity and the immune system is no exception.

I don’t work on Fridays anymore so last Friday afternoon I headed down to a primary care clinic to get some problems checked out. The primary care doctor was clearly knowledgeable, reassured me that I had no major problems, and asked me if there is anything else that he could do for me. At that point the conversation went something like this:

Me:  “Well I keep being told every other visit that I need a second Pneumovax vaccination and I need the second Shingrix vaccination. Is it possible get those today?”

MD:  “That should not be a problem”

Me:  “Is there any problem with getting them on the same day?”

MD:  “No you can get them both on the same day.”

At that point he pulled up the EHR and verified that I had a Pneumococcal Conjugate Vaccine (PCV13) on 1/11/2016 and a Pneumococcal polysaccharide vaccine (PPSV23) on 9/8/2010 and a previous Shingrix vaccine on 10/30/2019. He explained the rationale for the second PPSV23 vaccination.

MD: “Did you have any reactions to the first vaccinations?”

Me:  “Just a little pain at the injection site but nothing major.”

The nurse came in the room and asked me if I wanted the shots in the same arm or different arms.  She gave me the Shingrix injection in the left arm and the PPSV23 injection the right arm. I noted the time was 2 PM.  I have a history of anaphylactic reactions and an anaphylactic reaction to a second dose of anti-rabies duck embryo vaccine when I was in the Peace Corps. I forgot to bring an EpiPen, but there is a coffee shop just down the street. I spent an uneventful 40 minutes there (to get through that window) and then headed home.

About six hours later I started to get more intense muscle pain in both arms that eventually extended into the back and down the back. A short time later I started to get a headache. By 9 o’clock that night I was taking acetaminophen for those symptoms. I also noted that I was feeling physically ill and fatigued. The next morning I did not feel any better and continued to take the acetaminophen and added naproxen.  By 1 o’clock the next day - nearly 24 hours after the injection I started to get intense chills. It took my temperature and it was normal. I had put on outdoor clothing and sat next to the fireplace. I was shaking. It reminded me of when I had malaria back in 1975. In those days I had a cheap sleeping bag and crawled into that but eventually crawled across the floor into a tub of hot - water dragging the sleeping bag with me.  I had better resources now. I developed some tachycardia and felt very physically ill until about the 60 hour mark. At that point the chills stopped and the tachycardia resolved.

In the meantime I had solicited a number of medical and nonmedical opinions. One of the best internists I know told me that he advises patients take Shingrix vaccination but that they should plan on being out of commission for 2 to 3 days. He also does not recommend any other vaccinations with it because of the severity of the reaction. Several other primary care physicians have given me similar advice. I posted my experience on a listserv for psychiatrists and my Facebook site and several people had similar experiences. The physical illness caused by the immunizations was intense enough to take sick leave from work.

When I left the doctor’s office I was given “Vaccine Information Statements” that were both CDC documents.  One was entitled “Pneumococcal PolysaccharideVaccine - What You Need to Know” and the other was “Recombinant Zoster (Shingles)Vaccine: What You Need to Know”.  For the shingles vaccine the risk of reaction to the vaccine was listed as mild to moderate arm pain in 80% of people and side effects that prevented 1 of 6 people from doing regular activities that included fatigue, muscle pain, headache, shivering, fever, stomach pain, and nausea. The side effects were supposed to resolve in 2 or 3 days. By comparison the pneumococcal vaccine states that “less than 1/100 people develop a fever, muscle aches, or more severe local reactions”.

At a theoretical level it is interesting to consider the differences between both vaccines. In order to generate an immunological response, vaccinations need to create inflammation at the injection site. That typically requires an adjuvant. Adjuvants like aluminum compounds result in local cell death that leads to release of IL-1 family cytokines and danger-/damage associated molecular patterns (DAMPS). That in turn leads to T cell response and immunity (3). 

The adjuvants for these vaccines are significantly different.  The PPSV23 adjuvant is a standard alum based.  The Shingrix adjuvant is an ASO1B that is described as “ f 3-O-desacyl-4’-monophosphoryl lipid A (MPL) from Salmonella minnesota and QS-21, a saponin purified from plant extract Quillaja saponaria Molina, combined in a liposomal formulation. The liposomes are composed of dioleoyl phosphatidylcholine (DOPC) and cholesterol in phosphate-buffered saline solution containing disodium phosphate anhydrous, potassium dihydrogen phosphate, sodium chloride, and water for injection.” By comparison Zostavax the original shingles vaccine was live attenuated varicella-zoster virus without an adjuvant.  The Zostavax vaccination is much less effective, leading the CDC to recommend both doses of Shingrix, even if there is a significant non-allergic reaction to the first injection. 
Flu-like symptoms are an area great interest to me into a large extent they are cytokine mediated.  The top flow sheet at this post gives common cytokines that can cause flu like illness.  Given the complexity and sheer number of cytokines the scope of inflammatory cytokines triggering these reactions is not known.  Of the known cytokines from the Shingrix inflammatory reaction (4) it is likely that IFN- γ is a cause. The other interesting aspect of this response is that it is hypothalamically mediated.  The preoptic anterior hypothalamic area (POAH) has networks for heat production (shivering) and dissipation (vasodilation) (5) and both were affected in my situation. This area is described as being sensitive to a number of compounds including cytokines.  Other  cytokines may explain the associated flushing and sweating.

At the time this was posted I have been seen in the Urgency Room last night because my health plan was concerned about tachycardia and flushing.  The ED doc thought it was all a post vaccine reaction and did not do any further testing.  He said to come back if I got a rash, bloody urine, or a temp of 100.5.  I had the chills for about 8 hours at that point. I went to bed at midnight and woke up at 3AM sweating.  By 7AM, the tachycardia and flushed sensation and appearance were gone. Things were going well until this afternoon when I noticed the redness on the arm where I had received the Pneumovax (see photo).  I was seen in Urgent Care this time.  They had an alternate explanation for the inflammatory response, if the needle is withdrawn too quickly some of the vaccine and adjuvant gets deposited in subcutaneous tissue and leads to a broad inflammatory response.  They recommended an antibiotic (cephalexin) and prednisone just in case. I declined the prednisone and could not get the antibiotic filled anyway.  The pharmacy I use closes at 7PM and I got out of Urgent Care at 7:07.

What are the lessons from this adventure in vaccinations?  First off, as I have said repeatedly on this blog there are no guarantees in medicine. Everything is a probability statement.  In the case of Shingrix, I am taking a vaccination that may be 90% effective in preventing shingles but the trade off is that in clinical trials as many as 1 person out of 6 gets disabling side effects for at least 2-3 days. I have heard from some people where it lasts for 10 days.  Second, even though those are significant side effects shingles is potentially far, far worse. In the people I have treated, that includes months of disabling neuropathic pain, eye complications, facial nerve complications, and in some cases extensive testing just to find out what the problem was.  As an example, a 79 year old man had extensive testing for severe abdominal pain that was thought to be a malignancy that was ultimately diagnosed as shingles.  In the case of Pneumovax it is pneumonia, meningitis, sepsis and death. Case closed.  My memorable case there was an eldelry patient who presented to the emergency department with "agitation".  As the intern on Neurology I was called to see her.  By the time I arrived she was unresponsive.  Upon examination she had pus running out of her ear and nuchal rigidity. A lumbar puncture showed pneumococcal meningitis.  She survived a complicated course including acute respiratory distress syndrome (ARDS) but became completely deaf from the meningitis. Third, it is probably reasonable to not get both vaccinations at once. The physicians writing to me at this point have all been affected by complications they have seen in their patients who got Shingrix and they have seen it as a vaccine that has more than the ordinary amount of adverse effects compared with typical adult vaccinations.  Finally, what about the issue of repeat Pneumovax vaccinations?  It only comes up in cases where a person has COPD or asthma (me) and gets a vaccination before the age of 65 on that basis. Clearly, the arm rash here seems to indicate more of an inflammatory response on the Pneumovax side than the Shingrix in my case. Was it because of a robust antibody response after the initial vaccination?  I don’t have the answer to that question but if there are any immunologists reading this post – I would be very interested in your comments.

That is it for now.  Hopefully I am heading into work tomorrow morning.


George Dawson, MD, DFAPA




References:

1.  SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted), suspension for intramuscular injection.  FDA Package Insert   https://www.fda.gov/media/108597/download

2.  PNEUMOVAX® 23 (pneumococcal vaccine polyvalent) Sterile, Liquid Vaccine for Intramuscular or Subcutaneous Injection.  FDA Package Insert  https://www.fda.gov/media/80547/download

3.  Muñoz-Wolf N, Lavelle EC. A Guide to IL-1 family cytokines in adjuvanticity. FEBS J. 2018 Jul;285(13):2377-2401. doi: 10.1111/febs.14467. Epub 2018 May 3. Review. PubMed PMID: 29656546.



4. Cunningham AL, Heineman TC, Lal H, Godeaux O, Chlibek R, Hwang SJ, McElhaney
JE, Vesikari T, Andrews C, Choi WS, Esen M, Ikematsu H, Choma MK, Pauksens K, Ravault S, Salaun B, Schwarz TF, Smetana J, Abeele CV, Van den Steen P, Vastiau I, Weckx LY, Levin MJ; ZOE-50/70 Study Group. Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older. J Infect Dis. 2018 May 5;217(11):1750-1760. doi: 10.1093/infdis/jiy095. PubMed PMID:29529222.


5. Swaab DF. Autonomic Disorders in Handbook of Clinical Neurology, Vol. 80
(3rd Series Vol. 2) The Human Hypothalamus: Basic and Clinical Aspects, Part II,
2004, Elsevier, Amsterdam, pp351-370.




Supplementary 1:

Did not make it into work as expected on February 4. Went to see my primary care MD instead.  The erythema (redness) had not gone down and actually extended farther down the arm (I drew a line around it the night before).  No systemic symptoms but more redness.  Needed to know if the antibiotic needed to be changed and if prednisone was a good idea.

His conclusion - not an infection but inflammation from a reaction to the vaccine.  He has only seen a couple of reactions like this with Pneumovax and pointed out that it is given to immunocompromised people every ten years starting at a younger age.  He said to keep taking the cephalexin for a week but no prednisone: "I give prednisone to people with life threatening problems - not a red arm.  More medicine is not necessarily good medicine."

Work tomorrow. 

Supplementary 2:

New CDC Guidelines on Pneumococcal Vaccinations:



New Pneumococcal Vaccine Recommendations for Adults Aged ≥65 Years Old

PCV13. PCV13 vaccination is no longer routinely recommended for all adults aged ≥65 years.
Instead, shared clinical decision-making for PCV13 use is recommended for persons aged ≥65 years
who do not have an immunocompromising condition, CSF leak, or cochlear implant and who have
not previously received PCV13 (Table 1).

CDC guidance for shared clinical decision-making. When patients and vaccine providers engage
in shared clinical decision-making for PCV13 use to determine whether PCV13 is right for the specific individual aged ≥65 years, considerations may include the individual patient’s risk for exposure to PCV13 serotypes and the risk for pneumococcal disease for that person as a result of underlying medical conditions (Box).

If a decision to administer PCV13 is made, it should be administered before PPSV23 (5).
The recommended intervals between pneumococcal vaccines remain unchanged for adults without
an immunocompromising condition, CSF leak, or cochlear implant (≥1 year between
pneumococcal vaccines, regardless of the order in which they were received) (5). PCV13 and PPSV23 should not be coadministered.

ACIP continues to recommend PCV13 in series with PPSV23 for adults aged ≥19 years
(including those aged ≥65 years) with immunocompromising conditions, CSF leaks, or
cochlear implants (Table 1) (2).

PPSV23 for adults aged ≥65 years. ACIP continues to recommend that all adults aged ≥65 years
receive 1 dose of PPSV23. A single dose of PPSV23 is recommended for routine use among all adults aged ≥65 years (1). PPSV23 contains 12 serotypes in common with PCV13 and an additional
1 serotypes for which there are no indirect effects from PCV13 use in children. The additional
11 serotypes account for 32%–37% of IPD among adults aged ≥65 years (22). Adults aged ≥65 years
who received ≥1 dose of PPSV23 before age 65 years should receive 1 additional dose of PPSV23 at
age ≥65 years (2), at least 5 years after the previous PPSV23 dose (Table 1) (5).


Note:  In the above case of the vaccine reaction I received 1 dose of PPSV23 before the PCV13 and one dose after by a period of 4 years.  That is not consistent with the guideline but they  were no coadministered and there was a period of at least one year between injections (PPSV23 in 2010, PCV13 in 2016, and PPSV23 in 2020).