Sunday, February 15, 2026

Community Acquired Pneumonia - and How To Avoid it

 


Disclaimer:  Like all posts on this blog this is intended for educational and commentary purposes and is not medical advice in any form.  All medical decisions need to be made in collaboration with your personal physician who knows your history.  For reasons stated below - vaccination information and recommendations are also less clear than they have ever been due largely to political influences that can also affect physicians.

 

This a strategic post about pneumonia.  By strategic I mean I hope to clarify what it is and how to prevent it.  This is not about diagnosing and treating it.  Most people reading this blog either don’t need to know that or know a lot more than me about it. Instead, I hope to address three things – misinformation about it, barriers in the modern healthcare system to acute care, and how to prevent it.

My focus will be on community acquired pneumonia (CAP).  It is a term I am very familiar with dating back 40 years to med school and my medical internship. As an intern I carried around my copy of Sanford’s antimicrobial therapy and the relevant section of Phantom Notes which was basically an outline of the leading Internal Medicine text at the time.  Thirty percent of the people I admitted to the hospital had some kind of pulmonary problem.  Depending on who you read chronic obstructive pulmonary disease (COPD) is as high as the third leading cause of death worldwide.  Exacerbations of COPD were very common reasons for hospital and ICU admission. 

CAP by definition is acquired in the community and not in a hospital setting.  It can be cause by a range of microorganisms and host factors.  It can also develop in people with no known risk factors. Conventional wisdom used to be that the lung was sterile territory but now we know that it contains a low biomass microbiome consisting of bacterial, viral, and fungal elements that are there via microaspiration of mouth contents.  Local physiological changes can occur to change the microbiome, or pathogens can be inhaled that establish primary infections (1).   Certain lung diseases like COPD and asthma can also lead to selective proliferation of elements of the microbiome. 

The ability of the lung to repair itself after injury or infection is controversial. Some research suggested that the lung was permanently changed by infection.  One example would be the association of asthma with previous rhinovirus infection. More recent work suggests there is room for optimism if the regenerative capacity of the lung can be activated (2).  

My motivation for this post was a clinical trial I read in the New England Journal of Medicine.  It was about treating CAP in East Africa.  The research question was whether adding glucocorticoids to antibiotic treatment as usual would improve outcomes.  That study quotes the mortality of CAP as 25-30%. The study was conducted in Kenya.  2,180 study patients were randomized to standard care versus glucocorticoids.  All patients were admitted to a hospital and CAP was defined as “the presence of at least two of the following signs and symptoms for less than 14 days: cough, fever, dyspnea, hemoptysis, chest pain, or crackles on chest examination.”  Imaging was not a criterion for study entrance because it was not available in many settings.  They were started on the protocol within 48 hours of admission. Glucocorticoids were provided for free as one of five glucocorticoids in bioequivalent doses for a total of 10 days (including after discharge) in addition to standard care (6 mg of dexamethasone, 160 mg of hydrocortisone, 30 mg of methylprednisolone, 50 mg of prednisolone, or 50 mg of prednisone).  Standard care was antibiotic therapy per World Health Organization (WHO) guidelines (beta lactam and macrolide antibiotics). Exclusion criteria are available in the paper.

30-day mortality was the primary endpoint in an intent-to-treat analysis.  To get to the treatment population a total of 46,224 patients were screened.  Of the 2,180 patients mortality was 530 (24.3%) at 30 days.  246 of 1089 (22.6%) were in the glucocorticoid group and 284 of 1091 (26.0%) in the glucocorticoid group.  That translates to a hazard ratio of 0.84.  The authors explain the limitations (comorbid illnesses – HIV, hypertension) and advantages (large N, lower media age) of their study.  That seems like a slight reduction in mortality for the intervention, but the authors point out that several other studies had better results up to a 50% reduction in mortality with glucocorticoids and it is a low tech readily available intervention.

In looking at the side effects of glucocorticoids   Pulmonary tuberculosis and hyperglycemia were the most common adverse effects in the glucocorticoid treated group.  Pulmonary tuberculosis and acute kidney injury were the most common adverse effects in the standard care group. 

The striking part of this study for me are the mortality figures. Although the researchers emphasized throughout their study that this was a pragmatic trial in a healthcare system with fewer resources – the estimated mortality for community acquired pneumonia in the United States is 6% at 30 days for hospitalized patients but that increases to 34% at 30 days for patients who do not initially improve initially (4).  There are treatment guidelines for primary care physicians about who can or cannot be treated on an ambulatory basis.  Age is a risk factor for increased incidence of pneumonia with the rate increasing from 248 (all adults) to 634 (ages 65 to 79) to 16,430 per 100,000 after the age of 80 (5).  Pre-existing COPD increases the risk of hospitalization 9-fold.

There are characteristic patterns of pneumonia by pathogen based on the immune response.  Bacterial infections elicit an infiltration of neutrophils into the alveolar space in a pattern of lobar or bronchopneumonia that results in an exudate of dead cells and phagocytes in the alveolar space.  Viral infections cause an interstitial pattern of inflammation with lymphocytic cell infiltrates.  Identification of the pathogen is largely done on a clinical basis due to difficulty identifying the pathogens.  Indirect methods can be used like determining acute and convalescent phase antibodies to specific viruses. Both types of infection compromise normal physiology and can lead to hypoxia and in the case of bacteria secondary infections - like meningitis.      

Recent sporadic and annual viral pandemics have created a confluence of factors at the hospital that are best avoided.  The first is the use of broad-spectrum antibiotics.  Since a significant portion of people admitted with viral pneumonia develop hospital acquired secondary bacterial infections – antibiotics are given prophylactically to prevent that complication.  Increasing exposure to increasingly potent antibiotics leads to multiple drug-resistant bacteria.  The best pathway is to avoid getting the respiratory infection in the first place. 

The absolute best way to avoid is vaccinations.  Vaccinations are currently available for influenza, COVID-19 (Sars-CoV-2), respiratory syncytial virus (RSV), and Streptococcus pneumoniae (pneumococcal pneumonia and meningitis).  They have all been tested and offer relative protection (rather than absolute) against serious illness, hospitalization, and death, especially for adults 65+ years of age.  Vaccinations have become a mixed bag of accessibility.  On the one hand you can get them from pharmacies and that is a recent development.  On the other hand we have an elected government that has appointed a well known antivaccination promoter as the head of Health and Human Services – Robert F. Kennedy, Jr.  So far there have been restrictions on the COVID vaccination to people who are 65+ or have an underlying health condition.  Since the administration is apparently making health decision based on politics and ideology many states and professional organizations are publishing their own guidelines.  As an example here is a list of respiratory virus vaccination guidelines from the American Academy of Family Practice (AAFP).  The CDC still has pneumococcal vaccination recommendations for children less than the age of 5 and adults over the age of 50.

The University of Minnesota Center for Infectious Disease Research and Policy (CIDRAP) program has a good brief on the vaccine controversy and chaos introduced by the Trump administration and the lack of scientific origins at this link.

Apart from vaccinations risk factor modification should be considered.  If you were born and raised in American culture – it is important to realize that you have been socialized to expect to get sick in the wintertime.  I did not realize that until I was getting sick 2-3 times a year on the inpatient unit where I worked.  They were viral illnesses that took 2-3 weeks to recover from.  The building was made in an era where preservation of heat was the primary design goal.  There was minimal circulation of clean air or filtration.  My suggestions to improve the air quality were ignored.  The mini-epidemics were made worse by admitting people who were ill with respiratory viruses and not using any precautions to prevent the spread of those viruses.  The new personal time off (PTO) policies that make no distinction between vacation and sick days also lead to increased exposure to sick employees who would rather work sick than use PTO days for sick time.  Since the COVID pandemic even outpatient clinics ask questions every time they see you to minimize staff exposure to respiratory viruses.

Masks work.  They must be N95 masks and fit correctly but there is no doubt that they work.  These days it is common to see political arguments and in the extreme ridicule heaped on people who use them. Large scale uncontrolled studies are often cited as evidence that they are a weak intervention.  These studies are almost all self report with no measures of actual adherence to masking.  The best studies are done in a lab that look at filtering virus sized particles and there is no doubt they are equal to that test.  

Risk factor modification is probably important.  Cardiopulmonary diseases are significant risk factors for pneumonia – so maintaining the best possible treatment for those conditions is important.  Weight control and activity level are also important.  There is at least one study showing that 65+ year olds who maintain high activity levels have better immunity than those who do not.  The specific dose of exercise for that effect is unknown currently. 

Expert advice on vaccine allergies is an important point.  I have personal history of an anaphylactic reaction to anti-rabies duck embryo vaccine in 1975.  For the next 30 years I did not get a single vaccine against influenza because it was egg based.  I had innumerable episodes of viral illness that was probably influenza and decided to see an immunologist to see if I could be desensitized to eggs so I could get the flu vaccine.  When he confirmed that I could eat eggs without a problem he said that I would probably not have any problems with the vaccine.  He was correct and I have not missed an annual dose since.

Look for respiratory infection season onset and peaks.  They are typically available through your state public health department and the CDC. When I notice it – I change my routine to shop at nonpeak hours and wear a mask in stores.  In addition to protection from the airborne transmission route hand washing is also important.  Shopping carts, door handles, and other high traffic areas are unavoidable areas for direct contact transmission. That may include being in a public bathroom any time somebody flushes a toilet.  Keep in mind that there are number of circulating common cold viruses that include 4 coronaviruses that can make you very ill.

What about barriers to care in the current healthcare non-system in the US?  There are many since businesses have taken over health care in the past 40 years.  Healthcare is rationed by both businesses and governments with only a very grudging nod to quality. The most obvious example is avoidance of the emergency department if you need it.  Anyone with previous experience knows about waits in emergency departments and delays in care.  People avoid paramedics and ambulances out of fear they will be billed for that service.  If you expect that you are ill beyond a typical cold and have additional warning signs like shortness of breath – seek help immediately.  I have given that advice to many people and it is included in the final paragraph of this AMA information sheet.   Keep in mind that pneumococcal infection can also cause meningitis which is even a more significant emergency and those symptoms can include a severe headache and neck stiffness.  Maintain a low threshold for checking these symptoms out with your primary care physician’s office during working hours and their call line after hours. But if that is not available or able to give you an answer call 911 and get a paramedic there in person to advise you and advocate for you getting timely care.  Even in our fragmented healthcare system you do not have to go it alone.  

Finally – you must realize that the infectious disease space has been infiltrated by many people who do not belong there.  They have mixed agendas involving politics and health and wellness profits.  In some cases, they are just promoting themselves.  This varies from a kernel of truth rhetoric (eg. “most people who get this virus do not die”) to outright lies (eg. “this vaccine has never been adequately tested”).  There are many points in between such as “He died of pneumonia not COVID”.  In outrageous cases they have attacked and threatened public health officials.  It is important to recognize who these people are and why they must be ignored to preserve your interest and that is your personal health. 

I attached a list of the main respiratory pathogen vaccinations as a supplementary below. The indications are taken directly from the FDA approved package insert that is in turn based on clinical trials for efficacy and safety. There are significant differences between the FDA approved indications and eligibility as determined by various organizations. There are also links to those graphics in the appended material. Note that for the COVID vaccinations especially the eligibility can vary based on age, susceptibility status, and what has been referred to as mutual decision making. In my opinion this is basically slow walking vaccine denial in as eligibility. Essentially all medical decisions are based on informed consent as mutual decision making. I did not get a single influenza vaccine for 30 years because of mutual decision making that was based on inadequate information. I asked an Internist about what he would recommend in the cased of COVID-19 vaccinations and he said: “Definitely recommend for over 65. Recommend for patients with multiple comorbidities. Recommend for healthy young adults if they were healthcare workers, teachers or in an occupation with lots of exposure to the public.” Why are the eligibility criteria not that simple?  As far as I can tell the answer is politics.

That is my overall strategy to avoid pneumonia.  It is most important as you age into categories where your risk doubles (65+ yrs old) and increases 25-fold (80+ yrs old).  I use these strategies myself and have found them to be very effective.  And remember the overall strategy is to avoid the physical virus or bacteria if at all possible and failing that make sure your immune system is activated by a vaccination to attack it if you are infected.

 

George Dawson, MD, DFAPA

 

References:

1: Li, R., Li, J. & Zhou, X. Lung microbiome: new insights into the pathogenesis of respiratory diseases. Sig Transduct Target Ther 9, 19 (2024). https://doi.org/10.1038/s41392-023-01722-y 

2:  Ainsworth C. Lung, heal thyself. Nature. 2026 Jan 29;649:S9 – S11.

3:  Lucinde RK, Gathuri H, Mwaniki P, et al. A Pragmatic Trial of Glucocorticoids for Community-Acquired Pneumonia. N Engl J Med. 2025 Dec 4;393(22):2187-2197. doi: 10.1056/NEJMoa2507100. Epub 2025 Oct 29. PMID: 41159889; PMCID: PMC12659994.

4:  Peyrani P, Arnold FW, Bordon J, et al. Incidence and mortality of adults hospitalized with community-acquired pneumonia according to clinical course. Chest. 2020;157(1):34-41.    

5:  Jain S, Self WH, Wunderink RG, et al.; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415-427.


Graphic:

Pages from my trusty copy of Phantom Notes that I used on wards as a medical student.  I went back to check to see if community acquired pneumonia was a thing back then and it was not.  If you can read it they do discuss where it was acquired under Classification (D3).   According to PubMed that term was used just twice in 1981 - but became progressively more popular in the 1990s.


Note also that we have an expanded list of viral pathogens compared with 1981.

Phantom Notes Medicine 79-80 edition copyright Joe D. Glickman, Jr, MD All Rights Reserved.  


A Shocking Anecdote about Pneumococcus:

When I was an intern on neurology (1983) I was called down to the emergency department to assess a 70 year old woman for "agitation".   That was all they could tell me aside from the fact that her labs and exam were normal.  She was unresponsive, groaning softly and rolling from side to side on the bed.  I proceeded with my examination and found that she had a stiff neck and pus draining out of her left ear.  I called my two senior neurology residents and they came sprinting to the ED.  A quick gram stain of the pus showed gram positive cocci and we gave her 1 gram of IV chloramphenicol, did a lumbar puncture and transferred her to the Neurology ICU.  She subsequently developed ARDS and required transfer to the medical ICU for ventilatory support.  She was discharged a month later and was completely deaf as a result of pneumococcal meningitis.


Vaccines for Respiratory Tract Infections: Indications versus Eligibility:

 

Vaccine

Indication (From Package Insert)

Eligibility (From CDC)

Influenza

FLUARIX is a vaccine indicated for active immunization for the prevention

of disease caused by influenza A subtype viruses and type B virus contained

in the vaccine. FLUARIX is approved for use in persons aged 6 months and older. (1)

 - Fluzone High-Dose is a vaccine indicated for active immunization for the prevention of disease caused by influenza A subtype viruses and type B virus contained in the vaccine. (1) Fluzone High-Dose is approved for use in persons 65 years of age and older. (1)

Annual all adults

CDC Guidance

COVID

Moderna - SPIKEVAX is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

SPIKEVAX is approved for use in individuals who are:

• 65 years of age and older, or

• 6 months through 64 years of age with at least one underlying condition that puts them at risk of severe outcomes from COVID-19

 

Pfizer - COMIRNATY is a vaccine indicated for active immunization to prevent

coronavirus disease 2019 (COVID-19) caused by severe acute respiratory

syndrome coronavirus 2 (SARS-CoV-2). (1)

COMIRNATY is approved for use in individuals who are:

 65 years of age and older, or

 5 years through 64 years of age with at least one underlying condition

that puts them at high risk for severe outcomes from COVID-19. (1)

Adults should discuss with their health care provider to see if this vaccine is right for them.

CDC Guidance

RSV

-Active immunization of pregnant individuals at 32 through 36 weeks gestational age for the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age. (1.1)

- Active immunization for the prevention of LRTD caused by RSV in individuals 60 years of age and older. (1.2)

-Active immunization for the prevention of LRTD caused by RSV in individuals 18 through 59 years of age who are at increased risk for LRTD caused by RSV

Adults 75+

Adults 50-74 at increased risk

CDC guidance

Pneumococcus

Pneumococcal Conjugate Vaccines (PCV)

 

PCV15 (Vaxneuvance): Protects against 15 types of pneumococcal bacteria.  is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older.

 

PCV20 (Prevnar 20): Protects against 20 types of bacteria; it has largely replaced the older PCV13 (Prevnar 13). Prevnar 20 is a vaccine indicated for

• active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older. (1)

• active immunization for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in individuals 6 weeks through 5 years of age. (1)

• active immunization for the prevention of pneumonia caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 18 years of age and older. (1)

The indication for the prevention of pneumonia caused by S.pneumoniae serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F in individuals 18 years of age and older is approved under accelerated approval based on immune responses as measured by opsonophagocytic activity (OPA) assay.

 

PCV21 (Capvaxive): A newer vaccine approved in 2024 for adults, protecting against 21 types, including several strains not covered by other vaccines. CAPVAXIVE™ is a vaccine indicated for:

• active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A,

11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in individuals 18 years of age and older. (1)

• active immunization for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A,15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in individuals 18 years of age and older. (1)

The indication for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B is approved under accelerated approval based on immune responses as measured

by opsonophagocytic activity (OPA).Continued approval for this indication may be contingent upon verification and description of clinical

benefit in a confirmatory trial. (1)

Pneumococcal Polysaccharide Vaccine (PPSV)

PPSV23 (Pneumovax 23)

PNEUMOVAX 23 is a vaccine indicated for active immunization for the prevention of pneumococcal disease caused by the 23 serotypes contained in the vaccine (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F,14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F). (1.1)

PNEUMOVAX 23 is approved for use in persons 50 years of age or older

and persons aged ≥2 years who are at increased risk for pneumococcal disease. (1.1, 14.1)

Adults aged 50 or older according to CDC

 

 *High risk for severe outcomes:  For the comprehensive list of underlying medical conditions that place a person at risk for severe outcomes from COVID-19 see this CDC document: https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html

 FDA Vaccine, Blood, and Biologics Web Page:  https://www.fda.gov/vaccines-blood-biologics

 FDA Vaccines Licensed for Use in the United States:  https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-states

CDC Vaccine Schedule with graphic:  https://www.cdc.gov/vaccines/imz-schedules/adult-easyread.html

COVID recommendation:  “Adults should talk to their health care provider to decide if this vaccine is right for them”.

 AAFP Adult Vaccination Schedule with graphic:  https://www.aafp.org/dam/AAFP/documents/patient_care/immunizations/2025%20adult%20Schedule_NOV.pdf

COVID recommendation:  “1 – 2 or more (age >65) does of the updated 2025-2026 vaccine”.

 Minnesota Department of Health Adult Vaccination Schedule with graphic: https://www.health.state.mn.us/people/immunize/resprecs.pdf

COVID recommendation:  “All adults especially 65+ (2 doses)”.

 



 

Monday, February 9, 2026

Grandparents....

 



I was driving through my favorite coffee shop the other day.  The barista told me that I owed her a little over $10 so I gave her a ten and several ones.  I told her to “keep the change”.  She looked nervous as she collected the change from the cash register and put it in the tip jar.  She said: “Do you want your ones back?”  Of course I did not, but I knew what was going on.  It was the same thing that happened to me 60 years ago.

I was 14 years old and told that I could help my grandfather for the first time on a furniture moving job.  He had a hauling business and moved just about anything using a 1933 Diamond-T stake truck.  The job was only 3 blocks away, so I walked over there, but about ½ block away I froze.  I was nervous and even though I knew everyone at that job – I turned around until I heard: “Chorge!”  That was the way my grandfather pronounced my name.  He saw me turn and from a half block away encouraged me to keep moving in his direction.  Everything went well on the job, and it was the first time I got paid for doing real adult work.

Just a few nights ago I dreamed I was sleeping in the snow behind my grandparents’ home.  The ground was covered in about 4 inches of snow.  The exposed areas looked more like weeds than grass. As I slowly got off the ground – I realized I was on the property line of my grandparent’s neighbor Oliver.  Oliver was a machinist.  I remember being in his garage and seeing all kinds of machinist tools and lathes.  It was dark except for a single hanging light bulb.  There was a strong odor of oil in the air.  He did machinist work in his garage for a while after he retired – but then he and my grandfather just sat on a bench next to his garage and talked.  They were both old Scandinavians, but I never saw them drink coffee in the afternoon. I knew my grandfather always had plenty on board by that time of the day.

The years went by and I did more work for my grandfather.  At one time or another I was joined by four different uncles (Bill, Jim, Carl, Tom), my father (George, Sr), and another man (Elwood) who was there most of the time.  My grandmother kept the books.  Things seemed to be going well, but I know my grandparents were concerned about me at times.  When I was a freshman in college, I got very ill with appendicitis and sepsis.  After recovering from that illness – I did not feel like doing much.  I was laying in bed one morning and woke up to see my grandfather standing there.  His spine was bent two different directions from decades of heavy lifting. When he walked, he led with his hips, and his shoulders were never square over his lower body.  I could tell from that outline it was him even before I saw his face.

He started an awkward dialogue intended to motivate me.  He wanted to make sure that I was not taking his criticism of colleges and professors too seriously.  He wanted to make sure I kept going to college.  I thought my grandmother might have put him up to it but it was not her advice.  She would tell me to avoid roadhouses – usually when I stopped in to say hello on my way to a roadhouse.  The only reason he was there was that he heard I was not doing well – and he thought he could motivate me like that first day working with him.

The years went by quickly after that.  I completed college and was in the Peace Corps half the world away when I got the letter from my grandmother.  “Your grandfather died – he always loved you and worried about you.” – it read.  That was back in the 1970s and he was about the same age that I am right now.  My grandmother lived another 20 years, and I saw her whenever I could.  Work and geography create quite a barrier.  When my grandmother died, my aunt gave me a bundle of all the letters that I sent her from East Africa.  I have not been able to reread them.  

I woke up earlier this week with the thought: “I wish I could go back to the 1970s and see my grandparents to let them know I did all right.”  The only thing my grandfather knew was that he had a neurotic grandson who was hesitant, cautious, and reluctant in life.  My grandfather seemed like a nervous guy, but when he was college age, he was hanging off the side of an oredock on a swing – bolting together the top deck with an air powered wrench while he sat 90 feet above Lake Superior.  He told me a few horror stories from the industrial accidents that occurred on that site while I was on the mend in the hospital.  He told me a lot of stories about his friends that were mostly about fishing but also what we used to call power stories. Power stories in the North Country were tales of supernatural ability.  It was implicit that there could be some embellishment.  One of his favorites was telling me about a man who ran a hauling business with a team of dray horses.  From handling reins all day long he developed extremely callused hands to the point that anyone who shook hands with him would “just shiver.”

My grandfather had tattoos.  They were probably from sometime in the late 1920s or 1930s.  If you looked close enough you could tell they were women wearing grass skirts and dancing.  My grandfather never talked about the tattoos, and it was before the time they were popular again. I don’t have any and he never spoke to me about the subject and whether he recommended them or regretted his decision.

In my grandfather’s dining room, there was a picture of him and his younger brother when they were children about 5 and 7 years old.  The picture looked nothing like him as an adult.  He was bald and both children in the picture had abundant long wavy hair.  I have a post about a shocking event that occurred on the paternal side of the family.   On the maternal side, the shocking event was that my grandfather’s brother left town one day and was never seen or heard from again.  Nobody has any idea about what happened to him.  Like the event of my paternal uncle being killed as a child, the disappearance of my maternal grandfather’s brother was never mentioned over the 20 years that I knew him.

My grandparents talked about the Great Depression and how it affected them.  They were frugal even though my grandfather ran a business and had a payroll.  They had a woodburning stove in the kitchen and used that to heat bath water.  They used a large, galvanized steel tub to bathe in and did not replace it with a modern bath tub until late in life.    

When I saw that young barista, anxious about my tip – I imagined for a minute that I was a grandparent.  When I say imagined - I mean in retrospect.  In real time, I knew I had to reassure her that things were OK and that there were no problems.  I could see she was relieved and happy. And for a minute – I realized that I was living both my life and my grandfather’s - like on that day back in 1960 when he kept me on track.  I also realized why it was important to help young people through generosity – even if it helped for only a few minutes. 

I did a lot of research about grandparents for this post – but it turns out that the research says almost exactly what you expect it to say.   A good relationship with your grandparents especially on an emotional level is good for children, adolescents, and even adult grandchildren.  The relationship needs to be balanced.  Social media contains all kinds of stories about grandparents not having good experiences.  Complaining seems to be what social media is designed for.  There is also the standing joke about why grandparents have a more fun relationship with their grandchildren than the parents do - they do not have to set as many limits as the parents and can overindulge them.  My grandparents were generous with their time, energy, and finances when our family needed support.  They had a great sense of humor.  They taught us how to be kind and resilient.  There is some literature on how the grandparents benefit as well.  But I don’t think that they considered anything beyond doing the right thing for their family and the fact that they really liked us. 

And getting back to my coffee shop drive through – my grandparents taught me the importance of supporting younger struggling generations – whether you are their real grandparent or not.   

 

George Dawson, MD, DFAPA

 

Note on the Grandfather Transference:  Transference is an important concept and feature of psychiatric treatment.  Physicians and psychiatrists in particular notice that the way patients interact with them varies over the course of their career.  Early on it is common to hear statements like:  "You look too young to be a doctor."  That might reflect concerns about adequacy of training or experience that could affect the treatment relationship.  As mid-career years approach there are fewer comments about age, but potential concerns about being more career and revenue focused to the exclusion of individualized care and knowing the relevant details about the patient. In the years approaching retirement, I think people realize that you have seen a thing or two and are probably competent, caring, and looking out for their best interest. People seem less likely to challenge formulations or treatment recommendations.  They are less likely to become confrontational.  I have termed this last phase as a period of grandfather (or grandmother) transference.  I don't think it has been studied but it seems like it does enhance the therapeutic relationship. 

 Additional Note on Furniture Moving:  Over the years many people found out that I was a professional furniture mover and requested help with moves.  Requesting help and taking advice are two different things.  Invariably something was done against my advice that resulted in damaged furniture.  My grandfather and the men working for him were proud of the fact that there was never an insurance claim against them for damaged furniture.  If you think about it furniture is fragile - mirrors, finishes, pianos, TVs, dishes and other breakable items, spindly legs, and moved in the same truck with heavy appliances.  Just a slight shift in the load can result in massive damage. 

So if a professional furniture mover tells you that covering your very expensive piano with a bed sheet and baling twine is not a good idea - believe them.

That seems like another parallel to psychiatry.  It seems like a job so easy anybody could do it.  It is just common sense - right?


Supplementary:  Could not work it in above but many years ago I heard a very positive review of a book about Grandmothers on public radio.  I have never been able to locate that book.  If anyone has that reference please let me know.

 

Graphics Credit:  Peachyeung316, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons.


Tuesday, February 3, 2026

Combinatorics Summary....

 



 

I realized that I have a combinatorics thread running through my blog across several subjects.  I have been interested in combinatorics since I sent an email to Robert Spitzer on the various combinations of diagnostic criteria.  His only comment was “Interesting”.  Since then, I have commented on a post that purported to discredit psychiatric diagnoses based on combination of diagnostic criteria (too many), a study of the real combinations of major depression diagnoses, and character and word phrase combinations for encryption and password protection.  I went as far as getting dice and using them to construct passphrases of varying length using the Electronic Frontier Foundation (EFF) word list for that purpose.

If you have no experience with combinations or it has been a long time since your college statistics course – dice are a good place to start.  Each die has 6 sides with corresponding numbers. The total combinations possible are 6n, where n = the number of dice rolled at once.  The EFF world list is 6,667 word long and that happens to be 6^5.  So, to generate passphrases – 5 dice are rolled and the corresponding number is looked up on the word list and recorded.  The process is repeated until the desired phrase length is generated.  The only downside to this method is that some sites still insist on additional numbers and special characters.  They can still be inserted in the passphrase, but other systems like hexadecimal may be more convenient.  The advantage to passphrases is that they are theoretically easier to memorize and type without error.  That breaks down with very long phrases.

In biology and medicine, combinatorics can be applied at several levels. Some have more meaning than others.  On this blog, I responded to a paper suggesting that the possible combinations of diagnostic criteria meant that psychiatric diagnoses were meaningless and unscientific.  The lesson from this post is to have an idea of what you are counting and what it means. The total combinations of verbal criteria depend a lot on the phrasing and the total number of criteria whether large or small is not necessarily disqualifying as illustrated in this post.  The combinatorial upper limit can be unrealistically large based on how it is defined and just running the numbers does not mean that all possible combinations will be found.  There also seems to be some magical thinking involved – just because you count something does not say anything about what that means.  It is quite literally an exercise in the map is not the territory. 

I looked at a second paper where the authors looked at a lower number of combinations based on the DSM diagnostic criteria for major depression.  In that case the total number of diagnoses was much lower at 227 combinations.  The authors of that second paper did standardized interviews on 3,800 people and of the 1,566 with major depression – just 10 of those combinations accounted for 50% of the cases.  About ¼ of the possible combinations (57/227) did not occur in any group.  This paper is a stark reminder that just counting things in biology or medicine doesn’t necessarily mean anything.

That brings me to the concept of how we make sense out of the most valid combinatorial explosions in medicine. For me validity is baked into the biology and not a verbal description of things.  The backing for that comes from biological taxonomy and the fact that molecular biology and genomics is solving problems that could not be solved by the verbal description of direct observations in the Linnean tradition.  To that end I am reproducing a table below that is all about the polygenic risk for bipolar disorder. 



Note that in this table the authors are estimating the total possible combinations of 803 polygenes. The theoretical number of possible combinations can be calculated using the formula n! / r!((nr)!,where n represents the number of genetic variants analyzed in a study, and r represents the number of genetic variants per combination. In the case of  SNP genotypes,3^r.the formula is n! / r!(n-r)! ×3^r.  The authors point out that the lowest value for r is 2 but the upper limit is unknown.  They also show how the number of combinations can be limited experimentally.  Of the 57,911,211 combinations found only in patients and not controls they could all be random but there were a significant number of SNPs associated with different groupings in bipolar disorder.    

Using the equations from above in a more readable graphic form:

 

 

Substitution yields the following:

- from the top equation, for 100 variants the theoretical 10-variant combinations would be 1.73 x 1013

- from the bottom equation, for 500,000 SNPs analyzed there would be 2.3 × 1012 two-variant combinations and 3.4 × 1018 three variant combinations.

The application of practical measure includes scanning SNPs for varying combination lengths in the population of interest relative to controls. At lower numbers those combinations can be taken out scanning for longer combinations. A further simplification is to scan only for combinations found in patient populations.  An example of that study is included in the tables below for 803 SNPs in 607 bipolar disorder patients and  1,354 controls. 

Cluster and subgroup analysis is required in very heterogeneous conditions to analyze clusters containing a specific SNP, the distribution of SNP genotypes relative to controls, and cluster selection that contains an SNP for a specific biological function.  Using this kind of analysis 73/609 bipolar disorder patients had these clusters compared to none in the control population. 

While the SNP and variant analysis in 2017 is a good example of combinatoric applications – it did not address the problem of missing heritability.  Missing heritability is the difference between what is observed in familial heritability studies and what is predicted with genetic analysis.  Looking at the predictions from SNP based analysis only a low percentage of familial inheritance was predicted.  That improved with more sensitive analytical techniques that considered additional genetic mechanisms.  The additional mechanisms included SNV (single nucleotide variation), insertions or deletions (indels), SVs (structural variations), CNV (copy number variations), and STR (short tandem repeat (3-5).  Applications that identify all these variations are much more likely to predict the heritability of the pedigree than earlier techniques.  I hope to revisit some of these genetic innovations in an upcoming post about the DSM-6 proposals.

 

George Dawson, MD, DFAPA 

 

References:

1:  Mellerup E, Møller GL. Combinations of Genetic Variants Occurring Exclusively in Patients. Comput Struct Biotechnol J. 2017 Mar 10;15:286-289. doi: 10.1016/j.csbj.2017.03.001. PMID: 28377798; PMCID: PMC5367802.

2:  Koefoed P, Andreassen OA, Bennike B, Dam H, Djurovic S, Hansen T, Jorgensen MB, Kessing LV, Melle I, Møller GL, Mors O, Werge T, Mellerup E. Combinations of SNPs related to signal transduction in bipolar disorder. PLoS One. 2011;6(8):e23812. doi: 10.1371/journal.pone.0023812. Epub 2011 Aug 29. PMID: 21897858; PMCID: PMC3163586.

3:  Behera S, Catreux S, Rossi M, Truong S, Huang Z, Ruehle M, Visvanath A, Parnaby G, Roddey C, Onuchic V, Finocchio A, Cameron DL, English A, Mehtalia S, Han J, Mehio R, Sedlazeck FJ. Comprehensive genome analysis and variant detection at scale using DRAGEN. Nat Biotechnol. 2025 Jul;43(7):1177-1191. doi: 10.1038/s41587-024-02382-1. Epub 2024 Oct 25. PMID: 39455800; PMCID: PMC12022141.

4:  Wainschtein P, Zhang Y, Schwartzentruber J, Kassam I, Sidorenko J, Fiziev PP, Wang H, McRae J, Border R, Zaitlen N, Sankararaman S, Goddard ME, Zeng J, Visscher PM, Farh KK, Yengo L. Estimation and mapping of the missing heritability of human phenotypes. Nature. 2026 Jan;649(8099):1219-1227. doi: 10.1038/s41586-025-09720-6. Epub 2025 Nov 12. PMID: 41225014; PMCID: PMC12851931.

5:  Grotzinger AD, Werme J, Peyrot WJ, Frei O, de Leeuw C, Bicks LK, Guo Q, Margolis MP, Coombes BJ, Batzler A, Pazdernik V, Biernacka JM, Andreassen OA, Anttila V, Børglum AD, Breen G, Cai N, Demontis D, Edenberg HJ, Faraone SV, Franke B, Gandal MJ, Gelernter J, Hatoum AS, Hettema JM, Johnson EC, Jonas KG, Knowles JA, Koenen KC, Maihofer AX, Mallard TT, Mattheisen M, Mitchell KS, Neale BM, Nievergelt CM, Nurnberger JI, O'Connell KS, Peterson RE, Robinson EB, Sanchez-Roige SS, Santangelo SL, Scharf JM, Stefansson H, Stefansson K, Stein MB, Strom NI, Thornton LM, Tucker-Drob EM, Verhulst B, Waldman ID, Walters GB, Wray NR, Yu D; Anxiety Disorders Working Group of the Psychiatric Genomics Consortium; Attention-Deficit/Hyperactivity Disorder (ADHD) Working Group of the Psychiatric Genomics Consortium; Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Nicotine Dependence GenOmics (iNDiGO) Consortium; Obsessive-Compulsive Disorder and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium; Post-Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Substance Use Disorders Working Group of the Psychiatric Genomics Consortium; Lee PH, Kendler KS, Smoller JW. Mapping the genetic landscape across 14 psychiatric disorders. Nature. 2026 Jan;649(8096):406-415. doi: 10.1038/s41586-025-09820-3. Epub 2025 Dec 10. PMID: 41372416; PMCID: PMC12779569.

 

Graphics Credit:

Table 1 is reused from open access reference 1 above per  CC BY license (http://creativecommons.org/licenses/by/4.0/).