Clinical Trials Versus Clinical Treatment – Key Differences

This is always an ongoing source of debate in psychiatry – largely because of the forces that seek to delegitimize the field.  This post is not directed at them since they have a long track record of producing the same biased arguments.  This is my perspective as a person who has successfully treated people with severe psychiatric problems and been an investigator in clinical trials. I have first hand experience with the limitations of clinical trials and they can be considerable.  I am certainly not unique in that regard and it is important to know why those of us with that experience can dismiss headlines about psychiatric treatments not working as well as many of the associated reasons.

Let me preface these comments by saying that running a clinical trial at whatever level you are responsible for is hard work. I have been a co-principal investigator but most of my work was focused on research subject follow-ups and patient safety. I was the guy who got the call about unexpected side effects, lab reports, ECGs, and imaging studies. In those cases, it was my job to decide if the problem was due to the study drug (or placebo) or an intercurrent illness and decide if it was safe for the research subject to proceed.  If the decision was to stop the protocol, there is always at least one person who upset with that decision. There is a study coordinator who wants to maximize retention and study completers. There are the research subjects and their families who may consider the research drug the latest hope – even though they do not know if they are getting placebo. There are other investigators and research assistants who all want to maximize research participation.

Let me start by framing the main differences between research and clinical treatment starting at the top of the diagram.  Clinical trials are sampling the general population on a very specific feature.  In medicine that is typically a disease state. That selection process is modified to be even more stringent to eliminate other variables.  In the diagram this is indicated by the inclusion and exclusion selection criteria. That does not exist in clinical practice where any number of complicating factors need to be addressed in addition to the main indication for treatment. 

This recruitment phase in clinical trials is critical because there is limited funding, and adequate sample size must be recruited, and therefore there is an acceptable time frame. 70% of clinical trials do not recruit the number of subjects they need in the expected time frame.  Currently in the US, less than 3% of adult cancer patients participate in clinical trials (ref 1 p. 268).  In older research it was often stated that only 5% of eligible subjects participate in research. In my experience that number is accurate.  In some of my studies it approached 2% at times.  In other areas the numbers are higher but they typically max out at about 25% and there is a significant difference between experimental trials and retrospective or epidemiological trials that are less demanding.

The ratio of enrolled/screened is important because it suggests a skewed sample from the population that might be more evident if the reasons for declining research were explored.

Response to the recruitment problem is typically that it is taken care of by randomization – but is that accurate?  For example, if people do not want to take a chance on a new medication or randomization does that eliminate potentially good treatment responders from both arms of the trial?  If a trial is debated in the press – like many psychiatric trials are - will that increase the nocebo response in both arms? If a trial involves discontinuation or substitution of a current medication that had been somewhat effective does that lead to increased problems with nocebo effects and drop puts.  The impact on the physician-patient relationship can be affected by both offering and not offering trial participation.  Physicians are most likely not to suggest that stable well treated patients participate for altruistic purposes.  Recruiting pressure on the clinical trial team may lead them to accept suboptimal research subjects with a history of participation in multiple trials, subjects with milder illness or equal comorbidity (e.g. anxiety = depression), or subjects who are more likely to drop out.

These are just a few of the factors that can affect the recruitment and enrollment phase that are not very well investigated or recorded. Speaking from experience, I can say that what looks like an acceptable treatment protocol is often modified as investigators start to panic about low enrollment in the trial.

On the clinical side there are different problems. No matter how complex the patient’s situation there are typically waiting lists of patients to be seen by psychiatrists.  This is true even though only about 6% of the medical workforce that prescribes psychotropic medications are psychiatrists. There are no exclusion criteria and rather than the potential trial participant effect where trial participants are likely to do better even if the medication is ineffective (ref 1, p. 258) – patients referred to see psychiatrists are generally less healthy, more likely to have chronicity, less likely to adhere to treatment, more likely to have a substance use disorder, and more likely to have medical and psychiatric comorbidity.

In addition to the placebo and nocebo effects there are a number of lesser-known factors affecting the experience of people in clinical trials and clinical care.  Some of them will alter the entire trial sample.   For example, a recruitment bias due to failing enrollment can result in equivocal cases being enrolled (for example an adjustment disorder with depressed mood rather than major depression in a depression trial). These subjects are more likely to appear to respond to nonspecific factors.  Many people diagnosed with depression have a long history primary insomnia and may appear recovered if their insomnia is treated by the antidepressant or adjunct medications allowed in some protocols. I have participated in some protocols where all of the investigators were instructed to avoid any semblance of psychotherapy and not enroll anyone who might have a personality disorder.  These are some of the occurrences behind the scenes that can affect clinical trials.

The number of times a person volunteers for clinical research can be an issue. There is very little written about this, but there are some centers that specialize in research and often recruit healthy patients for early drug trials and compensate them. There are some online sites that say you can volunteer for as many studies as you qualify for in any given year.  There are obvious concerns about whether subjects need a break between trials as well as deception involved in gaining access to the trial, adhering to the protocol, and skewing the trial results (2-4).  I also have the concern that it is easy to fake some psychiatric disorders to get into a paid trial. The trials I have been in as an investigator were all through academic centers where reimbursement was primarily to cover travel expenses.  The professional patient role was probably less in those circumstances but it is an issue that is only covered in the research literature on a sporadic basis.

With the number of variables listed in the diagram – it takes a lot of thought to figure out the impact on the trial and clinical care.  It is useful to keep in mind a few overall points. First, there is a lot more going on in the trial than an effect based only on the biological effects of a medication (placebo, nocebo).  Second, clinical care is not like a clinical trial.  If someone is very ill and they are not responding to a medication or having side effects – a change needs to occur very quickly.  That is typically the same day on an inpatient unit or a day or two later in the outpatient clinic.  In a clinical trial, the subject can drop out or discuss other options with the investigator but those options are very limited and slow.  Major side effects typically need to be reported to the Human Subjects Board monitoring the research protocol, the protocol sponsor, and in some cases the FDA. Third, clinical care by its very nature incorporates many of the nonspecific factors associated with a nondrug positive response usually termed a placebo response. These same nonspecific factors can occur in psychotherapy trials as well as complementary medicine trials. 

Another important aspect of clinical trials is the measurement issue.  Various rating scales are typically employed as representations of psychiatric diagnoses. There are standardized and valid scales to measure adverse drug effects and, in some cases, more specific symptoms like sleep.  Global ratings by the investigators are added as an additional measure of validity.  These are all crude measures and unless subjects are selected specifically for a phasic severe disorder – the ratings will fluctuate significantly over the course of the trial based on various factors. In addition to the psychological, environmental, and biological factors some authors in medicine and biology have started to use the Heisenberg effect to describe this uncertainty. Since these measurements are not of discrete entities and cannot be represented by wave functions – this term is used at the level of a crude analogy for uncertainty in biological measurement.

Clinical care is much different.  There has only been a pretense of measurement.  There has been some publication of measurement-based psychiatry as an offshoot of evidence-based medicine.  I don’t think it offers much of an improvement over clinical psychiatry.  In psychiatry like all of medicine we are taught to recognize and respond to patterns not rating scales. I was reminded just this week of a referral I got of a patient who was described as having a histrionic personality disorder based on DSM criteria and some additional psychometric testing. It was apparent to me with a few minutes that the patient was manic and the correct diagnosis was bipolar disorder.  Psychiatrists are taught by seeing real patients, recognizing their problems, and organizing a treatment plan around those patterns. Referring to rating lists based on DSM symptoms that are in turn based on patterns in real people leaves a lot of room for interpretation.

The treatment aspect is also a critical difference.  There are few people who would want to receive treatment the way it is set up in clinical trials. People with any degree of a problem would not get adequate treatment. Most clinical trials are set up to see if there is an adequate efficacy and safety signal for the FDA to allow the medication on the market.  Post marketing surveillance is used to detect rare but severe side effects that might result in a new medication being withdrawn from the market.   

Clinical treatment is timely and effective in psychiatry.  Like the rest of medicine, it is not perfect and a lot can go wrong.  Based on my  experience as a researcher, a quality assurance reviewer, a teacher, and a colleague in large departments most people can count on finding a good if not excellent psychiatrist to provide effective treatment.  

 

 

George Dawson, MD, DFAPA

 

References:

1:  Piantadosi S.  Clinical Trials: A Methodological Perspective. 3^rd ed.  Hoboken, NJ: John Wiley and Sons, Inc, 2017: 886 pp.

2:  Shiovitz TM, Zarrow ME, Shiovitz AM, Bystritsky AM. Failure rate and "professional subjects" in clinical trials of major depressive disorder. J Clin Psychiatry. 2011 Sep;72(9):1284; author reply 1284-5. doi: 10.4088/JCP.11lr07229. PMID: 21951988.

3:  Pavletic A, Pao M. Safety, Science, or Both? Deceptive Healthy Volunteers: Psychiatric Conditions Uncovered by Objective Methods of Screening. Psychosomatics. 2017 Nov-Dec;58(6):657-663. doi: 10.1016/j.psym.2017.05.001. Epub 2017 May 9. PMID: 28651795; PMCID: PMC5680154.

4:  Lee CP, Holmes T, Neri E, Kushida CA. Deception in clinical trials and its impact on recruitment and adherence of study participants. Contemp Clin Trials. 2018 Sep;72:146-157. doi: 10.1016/j.cct.2018.08.002. Epub 2018 Aug 21. PMID: 30138717; PMCID: PMC6203693.

5:  Atkins PW.  Physical Chemistry. 5^th ed.  Oxford: Oxford University Press. 1994:  380-387.

 The issue of superposition is conflated with the uncertainty involved in biological measurement. It is the described as an analogy rather than the definition of superposition from quantum mechanics.  

Workforce Reference:  40,000 psychiatrists/290,000 nurse practitioners + 209,000 primary care physicians + 115,000 physician assistants – certified = 40,000/654,000 = 0.06 or 6%. 

Graphics:  I produced the above graphic with Visio.  Click to enlarge. 

What is Hostile Empathy?

 

I put up a few posts recently that emphasize empathy and why that is important in psychiatric practice.  I have also posted my favorite definitions by empathy – right out of Sim’s text on psychopathology (1).  I was surprised to see the term hostile empathy being used in social media today and in a publication (2) from the Bulletin of Atomic Scientists.  This post considers the original source, its use, and whether it really has anything to do with the technical definitions in psychiatry.

It turns out that the journey to hostile empathy takes you back.  Not back to the time it was used in psychiatry, but back to a discussion of ethnic violence in Indonesia (4) in the 1990s and before that to the early 1980s when “putting oneself in the shoes of a political adversary” was considered a form of realistic empathy as a possible basis for foreign policy.  That writing was done by military analysts, politicians, and anthropologists rather than psychiatrists.    

The original reason for this post is a paper on the Trump administration’s hostile empathy as evidenced by their reduction in aid to the needy both in the US and abroad (2) and the expected toll in morbidity and mortality. The author lists a source that estimates that 110,772 adults and 231,141 children had already died at the time of the paper’s publication largely through acute cuts in food and medical care needed to treat tuberculosis, HIV, malaria, diarrhea, and pneumonia. That is an obvious large human cost for what represents a tiny fraction of the federal budget. Tens of thousands of deaths are also anticipated from the administration’s cuts to Medicaid.  The bombing of Hiroshima and Nagasaki is given as a comparison where anywhere from 110,000 to 210,000 people are estimated to have died.  How can the intentional and ongoing humanitarian catastrophe by the abrupt cut in aid be rationalized?

The author suggests it is like the work of choosing nuclear targets during the Cold War.  The analysts had to distance themselves from any empathy they might have for their potential victims as they chose targets.  That distancing could be justified by the presence of a crisis and bureaucratization that rewarded people for target selection rather than empathy.  In the case of the Trump administration all the cuts are being rationalized as a crisis – even though they add significantly to the debt and could easily have been made through other mechanisms. The most obvious alternate mechanism would have been to not replace federal workers who were retiring or moving to different jobs. In the two most recent years that would have resulted in a decreased of 7.6% (147,000 positions in 2023) or 5.4% (115,900 in 2024).  It is now well known that despite their lack of transparency the savings from Elon Musk’s Department of Government Efficiency (DOGE) have been scaled back considerably from the original $2T dollar figure to a current $170B ( a 92% reduction).  Even that number is complicated by the costs of defending against several lawsuits and other miscellaneous charges that may have cost the taxpayers another $135B.  In addition, the Trump administration fired 18 Inspector Generals who saved the taxpayers anywhere from $90B to $183.5B without the disruption and compromised security.

Looking at the net effect so far – it seems that empathy is not at play at all.  The people receiving aid and the government employees affected were not consulted or understood at all.  In fact, a top administrator in the Trump cabinet said:

“We want the bureaucrats to be traumatically affected. When they wake up in the morning, we want them to not want to go to work, because they are increasingly viewed as the villains. We want their funding to be shut down … We want to put them in trauma.”  - Russell Vought – Director of the Office of Management and Budget 

This is not empathy or hostile empathy of any sort. This is open hostility to public servants in the service of an intolerant ideology by an administration that has so far shown that they have very few positives for the American people.  This cabinet member is also one of the architects of Project 2025 – a unilateral document designed to treat the Executive branch of government as an autocracy for the benefit of a particular ideology. Again – no empathy involved.    

A couple of issues came up and I made my way through the Bubant paper.  The first was the issue of word meaning for different groups and how language is used. Most people invoke Wittgenstein’s language games to make that point and I will join them.  In this case anthropologists and social scientists are clearly using empathic in a much different manner than psychiatrists. A psychiatrist does an interview seeking a deeper understanding of the person they are talking to.  They are looking for individual specific responses – life experiences, cultural factors, traits, symptoms, preferences, behaviors, and dynamics. The goal is to learn those well enough that the person would recognize them if the psychiatrist describes them (Sims).  Some may be recognizable at the group level. The author in this case is describing group characteristics and responses at a global level.  There is also the implicit understanding that empathy is generally used to assist or help the person who is being understood.  It is not used for hostile or nefarious purposes.   

Rather than empathy – hostile empathy is stereotyping and there is a much greater chance for error.  Further – it is evident that it is a recipe for divisiveness and authoritarianism that requires recognizing stereotypes at the grossest of levels. 

The obvious example in this case is proclivity for violence – especially the severe forms described in the letter.  It is difficult to believe that any significant population would not have groups that would never perpetrate this violence or support it.  This approach to populations always depends on probabilities.  There is a probability that a subgroup will respond to divisive rhetoric in a violent way and produce the desired result. By contrast, a psychiatric interview is focused only on the person in the room and what makes them unique. The intention from that knowledge is focused solely on helping that person at some level.  That renders the concept of hostile empathy meaningless.

One of the thought experiments to figure out what is really going on when people plan to bomb, attack, or otherwise incite violence in a population they dislike is looking at the decision making involved.  From a cognitive behavioral standpoint – it can easily be seen as a case of emotional reasoning.  Emotional bias is needed to some degree for most decisions but a heightened bias – by a crisis or appearance of a crisis – leads to more impulsive decisions.  The United States at the highest levels of government have made several including 3 unnecessary wars during my lifetime and the recent attack on Iran.  All these actions were based on false premises and resulted in significant loss of life, resources, and good will.  Keeley (4) has noted this recurrent pattern since the time of wars between prehistoric villages.  As he reviews the social, economic, and cultural factors associated with warfare empathy is not a factor.  He makes the case that prehistoric wars were as significant as modern warfare and probably more deadly.  On the question of war being common Keeley says this:

“Thus pacifist societies seem to have existed at every level of social organization, but they are extremely rare and seem to require special circumstances….. the idea that violent conflicts between groups is an inevitable consequence of being human or social life itself is simply wrong.  Still, the overwhelming majority of human societies have made war.  Therefore, while it is not inevitable, war is universally common and usual.” (p. 32)

Empathy of any kind is not a factor in war.  I would argue that the absence of any sustained successful peace initiatives in the world is related to two factors – the lack of emphasis on peace (even though the advantages are obvious) and a lack of any institution with the ability to enforce peace through dispute resolutions.  The driving force would appear to be the dispute and jumping to the conclusion that armed conflict is the only possible resolution.  Checks and balances on the decision makers within the country is also a factor.  In the United States, Congress is the only branch of government that has the authority to declare war and yet we have seen two Presidents in recent times start a war without that authorization. 

The lessons for psychiatry are clear.  If you are writing about empathy use the correct definition or at least a definition that is consistent with the psychiatric application.  Secondly, don’t accept loose definitions from other groups or contexts to apply to the field.  The best examples I can think of are epistemic and hermeneutic injustice.  These are non-psychiatric terms that are used to criticize the field. Outside criticism is common in psychiatry – but it does not need to be incorporated into the field particularly when the primary goal of the field is to understand each individual patient and their social and cultural context.   

 

George Dawson, MD, DFAPA

Supplementary 1:  I am of course aware of the fact that the authors of hostile empathy never intended to incorporate it into psychiatric technical jargon.  It merits consideration solely based on how non-technical terms show up in our papers.  I provided the examples of epistemic and hermeneutic but there are many more.  Deprescribing is a good example of a word and the associated rhetoric. Any psychiatrist who prescribes a drug knows how to stop it.  If you were ever an acute care psychiatrist – detoxification from drugs and alcohol is a necessary skill.  Many of those situations involve massive doses and polypharmacy.  And yet deprescribing was introduced a few years ago based on the false premises that psychiatrists do not alter medications (they just add more) and they do not know how to stop drugs. The reality is nobody knows more about it than acute care psychiatrists.  I have been presented with shopping bags full of medications for psychiatric, cardiovascular, endocrine, and neurological indications in the same confused patient who could not tell me what they were taking and I had to decide in the space of a few hours what to continue and what to discontinue. Physicians are not taught to deprescribe.  They are taught to discontinue medications.  I did that and taught people how to do it for over 35 years.  And yet we now find papers using the deprescribe term and writing like they are experts in a newly discovered field.  That is a significant problem with allowing people to invent the language of your profession.

Image credit:  My 2010 photo of the Painted Mountains in Denali National Park.  

References:

1:  Sims A.  Symptoms in the Mind: An Introduction to Descriptive Psychopathology. 3^rd ed. London: Saunders; 1995

2:  English E.  The consequences of the Trump administration’s hostile empathy.  Bulletin of the Atomic Scientists.  June 16, 2025   https://thebulletin.org/2025/06/the-consequences-of-the-trump-administrations-hostile-empathy/

3:  Nash HT. The bureaucratization of homicide. Bulletin of the Atomic Scientists. 1980 Apr 1;36(4):22-7.

4:  Bubandt N. From the enemy's point of view: Violence, empathy, and the ethnography of fakes. Cultural Anthropology. 2009 Aug;24(3):553-88. https://anthrosource.onlinelibrary.wiley.com/doi/10.1111/j.1548-1360.2009.01040.x

5:  Keeley LH.  War Before Civilization: The Myth of the Peaceful Savage. Oxford: Oxford University Press. 1994.

 

 

Pediatric Deaths From Firearms

 

If American society every becomes rational for any sustained period in the future – everyone living in the current epoch will be mocked.  We will be mocked for the absurd and obvious inconsistencies in society almost entirely driven by politics.  Guns, abortion, the discrimination and scapegoating of small segments of society, persistent racism, misogyny, a lack of concern for the disabled and disadvantaged, and a total lack of concern for the planet.  Sometime in the very near past – we stepped into a fantasy world where politicians could say anything – no matter how absurd, be believed, and get elected.

The lesson today is firearms and gun laws.  Over the course of writing this blog I have written about this many times. How the gun issue has been co-opted by one party and their judges.  That party has extremist views about gun laws and the Second Amendment.  Those extremist views endanger all of us and make the likelihood of ending school and other mass shootings impossible.

About a week ago, a paper came out in JAMA Pediatrics (1) that looked at the issue of permissive gun laws and pediatric mortality.  Guns in the United States are the number one cause of pediatric deaths in the country.  There are no other countries in the world where that is the case.  It speaks to these unique aspects of gun extremism in American culture and the degree to which people will rationalize gun access and laws that enable rapid deployment of guns with very little rationale.  Children and young men are dying in that crossfire and they have been for some time.

The research design of this paper was very interesting. It looks at the change in pediatric gun mortality over time stratifying states by their degree of gun permissiveness before and after the 2010 Supreme Court decision McDonald v. City of Chicago. In that case, a retiree and two additional plaintiffs brought action against the city of Chicago because they wanted to purchase handguns – but were not able to due to a citywide ban on issuing permits that began in 1982.  Details of the decision are included at the above link and my assessment is that the decision against the Chicago law was based on technical interpretations about whether gun ownership is a fundamental right. 

The overall effect of this decision was that many states changed their gun laws to make them much more permissive. Permissive gun laws are what I have been calling gun extremism.  Examples include mandatory issuance of gun permits and carry permits,  permitless carry laws, open carry laws (with or without permits including all types of firearms), stand your ground  or castle laws that say if you are armed you have no duty to retreat in certain environments, no bans on assault weapons, high-capacity magazine, or bump stocks, no red flag laws that remove weapons from individuals considered to be high risk, and no local laws that override state laws.  There is action in some cases to remove the ban on returning firearms to people convicted of domestic violence or drug charges.

You do not have to be a public health researcher to figure out what is wrong with these laws.  They basically return us to the days of the Wild West, where it took the local sheriff to come up with laws that guns needed to be checked at the city limits.  People roaming the streets carrying high-capacity automatic weapons is a recipe for disaster.  The current televised real crime genre – is an endless source of stories about gun homicides that occurred because somebody was angry, had access to a firearm, and impulsively shot somebody.  In the case of children and adolescents there is the additional risk of accidental shootings, suicide, and in some well publicized cases holding parents responsible for giving their child access to a gun that is subsequently used in the commission of a crime by that same child. When guns are everywhere – gun tragedies follow.

In this paper the researchers group states into 3 categories based on how permissive their gun laws have become since the MacDonald decision.   The categories were strict, permissive, and most permissive based on a classification protocol available in this supplement.    States rated as strict (total of 9) include:  California, Connecticut, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island.  States rated as permissive (total of 11) include:  Colorado, Delaware, Michigan. Minnesota, Nevada, New Mexico, Oregon, Pennsylvania, Vermont, Virginia, and Washington.  The remaining states were rated most permissive (total of 30) and include:  Alabama, Alaska, Arizona, Arkansas, Florida, Georgia, Idaho, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Mississippi, Missouri, Montana, Nebraska, New Hampshire, North Carolina, North Dakota, Ohio, Oklahoma, South Carolina, South Dakota, Tennessee, Texas, Utah, West Virginia, Wisconsin, and Wyoming.

What might a head-to-head comparison of states from each category look like.  Here are three states from the upper Midwest – one from each category (taken from supplementary data from reference 1).

Illinois (strict)	Minnesota (permissive)	Wisconsin (most permissive)
2013: Concealed Carry Act - Allowed concealed carry of firearms. 2013: Firearm Concealed Carry Act - strict requirements for obtaining a concealed carry license. 2014: Private Sale Background Check Law - Required private sellers to verify buyer's FOID card with state police. 2018: 72-Hour Waiting Period Law - Enacted a 72-hour waiting period for all firearm purchases. 2019: Firearm Dealer License Certification Act - Required gun dealers to obtain a state license in addition to federal license. 2019: Red Flag Law - Allowed family or law enforcement to petition for temporary firearm removal from at-risk individuals. 2021: Universal Background Check Expansion - Extended background check requirements to all private firearm transfers. 2022: Ghost Gun Ban - Prohibited the sale and manufacture of unserialized and untraceable firearms. 2023: Protect Illinois Communities Act - Banned sale, manufacture, and possession of assault weapons and high-capacity magazines. 2024: FOID Fingerprint Requirement - Mandated fingerprint submission for FOID card applicants   FOID = Firearm Owner Identification Card	2003: Minnesota Citizens' Personal Protection Act - Established a "shall-issue" system for concealed carry permits. 2005: Stand Your Ground Law - Expanded self-defense rights, removing the duty to retreat in certain situations. 2014: Domestic Violence Gun Ban - Prohibited individuals convicted of domestic violence or subject to protective orders from possessing firearms. 2015: Suppressor Legalization - Legalized the ownership and use of firearm suppressors. 2019: Gun Violence Protective Order Law - Allowed family members and law enforcement to petition courts for temporary removal of firearms from individuals deemed a risk. 2021: Capitol Carry Notification Law - Required the Department of Public Safety to notify permit holders about their right to carry in the State Capitol complex. 2023: Universal Background Check Law - Required background checks for private firearm transfers, with some exceptions. 2023: Red Flag Law - Implemented an Extreme Risk Protection Order system, allowing courts to temporarily remove firearms from individuals deemed a significant danger. 2023: Safe Storage Law - Required firearms to be securely stored to prevent unauthorized access, especially by minors. 2024: Ghost Gun Regulation - Restricted the sale and possession of unserialized firearms and unfinished frames or receivers.	2011: Concealed Carry - Legalized concealed carry of firearms with a permit. 2011: Castle Doctrine - Expanded self-defense rights in one's home, vehicle, and place of business. 2015: Waiting Period Repeal - Eliminated the 48-hour waiting period for handgun purchases. 2015: Switchblade Legalization - Legalized the possession and carry of switchblade knives. 2017: Constitutional Carry for Knives - Removed restrictions on carrying knives, including in a vehicle. 2018: Extreme Risk Protection Orders - Implemented "red flag" law allowing temporary removal of firearms from individuals deemed a risk (Note: This may have faced legal challenges or implementation delays). 2021: Second Amendment Sanctuary - Some counties declared themselves Second Amendment sanctuaries, though not at the state level. 2022 (L): Campus Carry Proposal - Significant discussions about allowing concealed carry on college campuses, though it may not have been enacted. 2023: Universal Background Checks - Implemented background checks for private gun sales (Note: If not enacted, this was a significant proposal during this period).

 

Note that there is significant overlap in terms of gun permissiveness.  For example, all states now have concealed carry laws.  Illinois was the last state to legalize this but all 50 states legalized concealed carry within a period of 10 years.  The creates the obvious question of how we all survived without concealed carry for a period of 222 years after the Second Amendment was ratified?  Minnesota and Wisconsin both have stand your ground laws.  Stand your ground and castle laws are euphemisms for shoot first and ask questions later.  All 3 states have red flag laws that allow for gun removal from high risk individuals but only one state mentions domestic violence as a condition.  Illinois has a FOID (Firearm Owner Identification Card) requirement.  Minnesota used to have one in order to purchase firearms but currently the concealed carry permit serves that purpose. Minnesota also allows businesses to post whether firearms can be carried on their campuses – but there is no enforcement.  Any way you look at these comparisons – the last 20 years has resulted in an unprecedented growth in firearm access.

The study period was 1999-2023 and during that time there were 41,012 pediatric firearm deaths accounting for about 4% of the total mortality.  Expected mortality calculations were done comparing the pre-decision period (199-2010) to the post decision period (2011-2023) and excess mortality was determined.  Incident rates as deaths per million were calculated based on the populations in each study period.  The firearm mortality crude rate increased in 33 states (see Table. Incident Rates Pre– and Post–McDonald v Chicago With Incident Rate Ratios).  Suicide and homicide by firearms both increased.  The most permissive states had the greatest number of deaths due to firearm suicide and homicide..

That authors list three minor limitations to their study, but seem to omit a major one and that is a control or no-gun category.  That may seem like a truism – how can you have gun related suicides and homicides if you have no guns?  One estimate is to compare firearm mortality to peer countries like the graphic from the Kaiser Family foundation at the top of this post.  The US child and teen firearm mortality rate is 10 to 200 times that in peer countries. The same is true for adult gun homicides and suicides.  All of those thousands of excess child deaths are due to easy gun availability in the US that is getting even easier.

We have a grim reality of a country that is chock full of guns to the point that we are trying to establish a dose-response curve. We are doing that exercise in a landscape that is still driven by gun extremists wanting even more permissive gun laws. Common sense has clearly been suspended in favor of political convenience in the US when it comes to guns.  Until it returns America’s children will pay the price in the form of completely unnecessary deaths and the ruined lives and families of the both the victims and perpetrators.

 

George Dawson, MD, DFAPA

 

References:

1:  Faust JS, Chen J, Bhat S, Otugo O, Yaver M, Renton B, Chen AJ, Lin Z, Krumholz HM. Firearm Laws and Pediatric Mortality in the US. JAMA Pediatr. 2025 Jun 9:e251363. doi: 10.1001/jamapediatrics.2025.1363. Epub ahead of print. PMID: 40489107; PMCID: PMC12150223.  

Graphics Credit:

Excellent analysis of child firearm death rates compared to peer countries is from the Kaiser Family Foundation at this link:  https://www.kff.org/mental-health/issue-brief/child-and-teen-firearm-mortality-in-the-u-s-and-peer-countries/

Use here is per the CC BY-NC-ND 4.0 license:  https://creativecommons.org/licenses/by-nc-nd/4.0/

No changes were made to this graphic downloaded on June 16, 2025.

My Diet - A Work In Progress

 

The easy way to eat all your fruits and vegetables….

 

Diet is endlessly debated in the US.  The health and wellness industry is three times larger than the pharmaceutical business. Much of their focus is influencers telling you about what you should eat and what supplements to take. They don’t let science or conflict of interest get in their way. 

For most of my life – I did not eat correctly.  I ate carbohydrates; some fish but usually dairy based proteins and too much sugar sweetened foods.  I always rationalized it as a cultural or genetic distaste for vegetables and fruits were just too problematic to store.  I read all the papers on diet and the advantages of a well-balanced diet.  That led to some gradual improvements. 

About 40 years ago I stopped eating processed meat products like hot dogs, sausage, and pepperoni.  30 years ago, I stopped eating beef.  20 years ago, I started to cut sugar sweetened foods way back to reduce gout attacks and minimize body weight fluctuations between cycling and skating seasons. 15 years ago, I started to eat a salad every day that consisted of lettuce, olives, and matchstick carrots.  Then about 3 years ago, I was at a restaurant and had a blueberry burrata salad made with spring greens and decided that blueberries needed to be in all my salads.  For the past two years my typical salad consists of tri-color slaw, blueberries, a light raspberry vinaigrette, and croutons.  I ate about 120 lbs of blueberries last year. 

My main protein source consists of Greek yogurt, skim milk, and eggs.  I do eat chicken and fish when available.  The yogurt ranges from 15-25 g of protein per serving and I eat 3 servings per day.  For breakfast I eat yogurt mixed with a combination of blueberries, blackberries, and raspberries.  I am considering expanding the berry selection to black currants and strawberries.

I don’t need a lot of variation in my diet. I was in the Peace Corps and ate homemade French Fries every day and a grilled cheese sandwich. Powdered milk was an additional protein source. I still eat desserts now and then and sprinkle chocolate chips on my yogurt and call that dessert.  I eat large restaurant salads made with spring mix generally because of the storage problem with spring mix.  I also tend to eat beet salads that are popular in Minnesota restaurants. Cubed beets drenched in ice cold vinaigrette with spring mix is a fantastic salad.  The tri-color slaw lasts longer and I can generally expect to eat it all (5 servings) before it goes bad. I have had too much lettuce go bad in about 3 days and by the official expiration date it looks like a bag full of motor oil.  I regularly eat large bean (black, chili) burritos, nachos with beans, and just plain beans.  I drink 2 cups of coffee per day – not because I like it but for the antioxidants. It must be hazelnut flavored.

I decided to post this today because of two reasons.  I just got back from my annual checkups at the Mayo Clinic and had to answer their nutritional questionnaire twice.  One of the questions focused on combined vegetable and fruit consumption.  They defined serving size as a tennis ball sized volume of the fruit or vegetable and that is somewhat controversial.  Some have the opinion that the volume of a tennis ball is ½ cup and others think it is closer to 1 cup.  When I look at a measuring cup my portions are easily closer to the 1 cup size, although in the case of tri-color slaw (carrots, red cabbage, green cabbage) it gets complicated.  

On the Mayo survey – you can land on the 2-4 or 4-6 portions per day.  I tallied it up as red cabbage, green cabbage, carrots, blueberries, blackberries, and raspberries or a total of 6 portions per day.  On their extended survey I got credit for low fat dairy consumption and eating nuts (cashews, pistachios, pecans, Brazil nuts, almonds, pine nuts, walnuts) – but lost credit for eating cookies (Animal Crackers, ginger snaps) nearly every day.  In the end I was rated as having a moderately good diet.

The second reason is to illustrate that you can overcome a bad diet gradually over time by finding something that you like. I always preferred carbohydrates as a calorie source but at some point – I came to the realization that even if potatoes were a healthy food – eating them deep fried or drenched in butter or in the case of sweet potatoes coated in brown sugar and butter probably did not add much nutritional value.  I have never been much of a meat eater.  The nuts and berries really broadened my horizons and markedly improved the taste of cabbage and leafy green vegetables. I have the advantage of being able to eat the exact same thing every day without the need for variation. I heard David Lynch describe this once.  He ate a chocolate malt and a grilled cheese sandwich every day for years. 

There are a couple of related current issues that are relevant.  Lately there is a lot in the media about processed foods. They are simply defined by having a lot of additives to enhance flavor or shelf life.  It is hard to avoid them, but the bulk of my diet has none. All the berries are frozen and the only ingredients are the frozen berries.  The Greek yogurt contains stevia – a natural sweetener but no artificial sweeteners. The slaw mix is only cabbage and carrots. The salad dressing contains the usual components.  I drink the occasional zero alcohol beer for additional antioxidants.  Although I do not have a specific antioxidant strategy – I am genetically loaded for a lethal neurodegenerative disease that I really hope to avoid (see Supplementary 2 below).  Like all these diseases oxidative stress is considered a potential mechanism so the antioxidants from this diet can’t hurt.

That is the diet I have come up with after decades of trial and error.  I am not recommending it to anyone else or suggesting that it will work for anyone but me.  It is not for anyone who needs a lot of variation in their diet.  You will also have a hard time keeping your teeth white.  The berries in this diet are one of the few things I have found that can stain Corelle dishware.  

In the end I have a moderately good diet according to Mayo and would never have guessed that I would land there. It took about 50 years to piece it together.

 

George Dawson, MD, DFAPA

 

References:

1:  The Mayo Clinic Diet Score (test your diet):  https://diet.mayoclinic.org/us/get-my-free-diet-score/

2:  Carlsen MH, Halvorsen BL, Holte K, Bøhn SK, Dragland S, Sampson L, Willey C, Senoo H, Umezono Y, Sanada C, Barikmo I, Berhe N, Willett WC, Phillips KM, Jacobs DR Jr, Blomhoff R. The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J. 2010 Jan 22;9:3. doi: 10.1186/1475-2891-9-3. PMID: 20096093; PMCID: PMC2841576.

3:  The Antioxidant Food Table, Carlsen et al. 2010. the main results of the present study; the table includes all the 3139 products with product descriptions, details and antioxidant analysis results, categorized into 24 categories and arranged alphabetically within each category

https://pmc.ncbi.nlm.nih.gov/articles/instance/2841576/bin/1475-2891-9-3-S1.PDF

4:  Ejaz A, Waliat S, Afzaal M, Saeed F, Ahmad A, Din A, Ateeq H, Asghar A, Shah YA, Rafi A, Khan MR. Biological activities, therapeutic potential, and pharmacological aspects of blackcurrants (Ribes nigrum L): A comprehensive review. Food Sci Nutr. 2023 Aug 15;11(10):5799-5817. doi: 10.1002/fsn3.3592. PMID: 37823094; PMCID: PMC10563683.

5:  Singh M, Arseneault M, Sanderson T, Murthy V, Ramassamy C. Challenges for research on polyphenols from foods in Alzheimer's disease: bioavailability, metabolism, and cellular and molecular mechanisms. J Agric Food Chem. 2008 Jul 9;56(13):4855-73. doi: 10.1021/jf0735073. Epub 2008 Jun 17. PMID: 18557624.

6:  Spreng S, Dawid C, Dunkel A, Hofmann T. Quantitation of Key Antioxidants and Their Contribution to the Oxidative Stability of Beer. J Agric Food Chem. 2024 Jul 24;72(29):16423-16437. doi: 10.1021/acs.jafc.4c01000. Epub 2024 Jul 15. PMID: 39010731; PMCID: PMC11273605.

Graphic Credit:

Click on photo to see photographer and CC license for use.  It is used as is with no modifications.

Supplementary 1:  I have attached a brief but selective table on the antioxidants in my diet. The antioxidant literature is interesting to an old chemist like me because the reported values depend on what food was analyzed, the extraction methods, what chemical group is analyzed, and the reporting methods.  As an example, on reporting the Antioxidant Content column below reports mmol/100g (from reference 3).  Many papers will report mg/100 g instead. 

The analysis in reference 2 was spectrophotometric based on the reduction of Fe³⁺TPTZ (2,4,6-tri-pyridyl-s-triazine) complex to Fe^2+--TPTZ complex that results in a blue solution that can be measured at 600 nM and the content estimated in mmol. The 100g is the amount of each sample extracted for this determination. That main limitation of this assay method is that it will not measure glutathione or other sulfhydryl groups due to the redox potentials, but some of these compounds can interact and lead to overestimates of the antioxidant content.   

The specific groups of antioxidants in column 2 are generally polyphenols with the capacity to transfer electrons and buffer what are known as Reactive Oxygen Species (ROS) that cause oxidative stress.  Any one of the foods in the table can be searched and you probably will be able to find a specific paper about the antioxidant content ranging from basic (like the 20 foods with the highest antioxidant content) to highly technical papers on the redox (oxidation-reduction) equations and potentials of these compounds.

Food	Antioxidant Content mmol/100g (3/5)	Antioxidant Mix:  Anthocyanins, Flavonols, Flavone, Flavanones, Isoflavones, Catechins, Proanthocyanidins,  PP polyphenols
Red cabbage	0.8/ 2.153	F, Cat
Yellow cabbage	0.15	Kaempferol, quercetin, apigenin
Carrots	0.02	Kaempferol, quercetin, and apigenin, cyanidin
Beets	1.50	A
Peas	0.61	PP
Corn	0.20	PP, vitamin C
Blueberries	7.13/ 2.159	A, F, Pro
Blackberries	5.98/ 3.99	A, F, Pro
Raspberries	3.46/ 2.334	A, F, Pro
Strawberries	5.44/ 2.159	A, F, Pro
Black Currants		A, F, Pro
Walnuts	1.27/ 13.126
Cashews	0.66	cardanols, cardols, phytosterol, triacontanes, anacardic acid
Pecans	9.67	Tocopherols, PP
Pistachios	1.43	A, PP
Pine Nuts	0.77	Polyphenols, xanthenes, carotenoids, tocopherols
Brazil nuts	0.47	Se, vitamin E, PP
Almonds	0.26	caffeic acid, sinapic acid, ferulic acid, p-coumaric acid
Red Beans	0.33	Delphinidin, cyanidin, procyanidin, phenolic acids
Chili Beans	0.26	gallic acid, rutin
Coffee filtered	2.60	chlorogenic acids, caffeine, nicotinic acid, trigonelline, tocopherols, cafestol, kahweol
Chocolate chips 70%	10.74/ 4.188	Pro
Bakers Chocolate	10.47/ 4.188	Pro
Diet Pepsi	0.04	caffeine
Yogurt Greek Zero Fat	0.06	Bioactive peptides
Stevia	0.04	Stevia glycosides
Chicken	0.02	Selenium, niacin (vitamin B3), 2-oxo-imidazole-containing dipeptides (2-oxo-IDPs), vitamin E, carotenoids
Fish – Walleye	0.04	vitamin E, peptides, glutathione peroxidase, superoxide dismutase, ubiquinones, and catalase
Eggs – Whole	0.06	ovalbumin, ovotransferrin, phosvitin, phospholipids, vitamin E, vitamin A, selenium, and carotenoids
Pizza/marinara sauce	0.88	Lycopene, PP
Potato	0.33	A, carotenoids. PP
Baked Sweet Potato	0.79	A, PP
Beer (zero alcohol)	0.10	hordatines A–C, saponarin, and quercetin-3-O-β-d-(6″-malonyl) glucoside

 

Supplementary 2: 

In the above post I described being at high risk for a neurodegenerative disease.  The following graphic is a polygenic risk analysis of my DNA that shows I am in the 100th percentile risk for amyotrophic lateral sclerosis or ALS - a fatal neurodegenerative disease.  There is no known treatment or cure and dietary factors play an uncertain role.  Environmental factors including diet are thought to be an important factor in all neurodegenerative diseases despite the clear biological components.