Thursday, November 3, 2022

No Way To Run A Democracy.....

 



 

CBS news came out with an analysis this morning that most Republican mid-term election candidates are election deniers.  That is 308 out of 597 total.  They agree with former President Trump that he actually won the 2020 election, despite the fact that there is absolutely no evidence to support that claim.  The evidence is lacking even when analyzed by Republicans and judges and attorneys who are Republican appointees. When that claim is reported in the news these days it is characterized as a lie. Even apart from the news media, the January 6th Committee has presented direct evidence that this claim was inaccurate and had no supporting evidence and that it also formed the basis for the coordinated attack on the Capitol and an attempt by former President Trump and his associates to overthrow the newly elected government of the United States.

What should be most concerning for any citizen of the United States is that attempted insurrection. There is a good chance that if the current crop of Republican candidates – most of whom are overt election deniers become the majority in the House that former President Trump and his associates will not be held accountable for this action. That is unprecedented in any democracy and it flaunts the rule of law and political convention of the United States. If the insurrection had succeeded – the United States as we know it would cease to exist. Democracy instead would be replaced by a Republican party of moral and gun extremists.

Instead of focusing on preserving the Republic – voters seem focused on the economy and inflation – as though any group of politicians has a more favorable history in that area. Over the course of my lifetime, we have had worse inflation, much worse unemployment, 10 recessions, 2 economic crises that nearly collapsed the world economy, and 30 yr fixed mortgage rates at least twice as high as they are now.  The people who saved the economy were professional economists from the Federal Reserve who are appointed and not elected officials. Elected officials consistently have the opportunity to pass legislation to reduce financial market risk due to speculation, but they seem to lose interest every time one of these crises has passed.  In this case both inflation and the possible recession can be explained by historical events (pandemic, Russian invasion of Ukraine) affecting the supply side and driving up prices. Rising interest rates to decrease demand and reduce inflation have made increased the cost of borrowing and that comes following a long period of artificially low interest rates that included low interest rates for savings accounts. In some cases, money market and bond funds were paying negative interest.  

I present the following graph as economic evidence. It is not exhaustive but it illustrates my point. I thought about adding a timeline of Federal Reserve Chairs but ran out of time. The national debt increases substantially under all presidents. The recessions are the shaded areas. Major crises in the economy occurred with the Savings and Loan Crisis (1982-1989), Long Term Capital Management liquidation (1998) and the Subprime Mortgage Crisis of 2007-2010.  The graph extends to August of 2022 with unemployment at 3.5% and Sticky Price Consumer Price Index of 6.39%.   Republican politicians are saying this is the highest inflation rate in 40 years.  What they are not saying is that it is also the highest rate of corporate profits in 70 years and the Federal Reserve has made interest rate increases that are already taking effect in the housing market. (click to enlarge)



I say that the voters seem focused on the economy because it is hard to get valid news about voter preferences from major networks focused on either balancing one party against the other (when no such symmetry exists) or acting essentially like the public relations department of the Republican party. Viewers used to be able to turn on the news and watch reliable journalists deliver the facts, but now they have a choice to listen to a broadcaster who parrots their political ideology. The facts take a distant second place.  There is no clearer example than election denial and all of its ugly correlates like voter suppression and political violence. 

There is only one party that has multiple members endorsing both of those options.  To listen to some of those candidates today – they make it seem like the opposition party has similar problems. There were no Democrats advocating for the violent overthrow of the US government.  There were no Democrats addressing violent groups and suggesting that they “stand by”.  There were no Democrats writing and passing permitless carry gun laws at a time when gun homicides and suicides are high and school shootings continue unabated.  There were no Democrats passing laws that allow heavily armed men wearing body armor and carrying assault weapons to gather in proximity to a legislative body and intimidate them. There is no symmetry between parties on the issue of political violence, gun violence, and the orderly transitions between elections. 

I could continue but realize that this scarcely read blog and the lateness of this post will probably not change much. I will end by posting what I consider the top issues to be in order of importance. I have posted before that I am a long time small “i” independent but in the current Constitutional Crisis I don’t have much of a choice and I have already voted. The vote I cast last week required 2 forms of ID, my address had to be confirmed in an electronic database and I had to sign a registry and one of the two envelopes containing my paper ballot.  That sealed paperwork was directly observed and signed off by an election worker.  This is what I voted on:

1:  Preservation of American Democracy. No insurrection against the government can stand and none of the conspirators should go unpunished.  Any party claiming to be the Law and Order party should understand this.  That party is trying to make crime an issue and it is hard to say if the media or the GOP is the reason for this focus - but the reality is that there has not been an increase in violent crime and there has been a 30 year trend in a positive direction. 

2:  Voter Rights. The Big Lie about the 2020 election was a variation of the big lie about election problems in the United States.  That lie is used to restrict access to voters and make it more difficult for citizens to cast their ballot. Lower income Americans are disproportionately affected.  A variation on that theme is intimidating voters and election officials. That is an ongoing process and it is encouraged by politicians spreading the Big Lie about both the election process and the integrity of the voting process. There is no evidence that either has been compromised. 

3:  Civil Rights.  The unprecedented attack on Roe at the level of the Supreme Court is really the culmination of Republican activism dating back to the Carter administration. At the time a Republican activist convinced fundamental Christians that they should be politically interested in the abortion issue and it was used to attempt to protect school segregation. They created one of the most divisive issues in American politics to advance their interests and made it seem like it was a religious issue.  This is a doubling down of moral extremism.  In other words moral superiority to cover an essentially immoral act.  There are not many positions that are more cynical.

4: Gun Regulation. Gun carnage continues unabated and the GOP and their justices in the Supreme Court have no reservations about allowing it to continue.  Republicans everywhere are rationalizing it as a problem with mental illness, when the prevalence of mental illness is the same across all countries and only the United States has mass shooters shooting children on a regular basis, gun homicide as a leading cause of death in children and young black men, and extremely high levels of gun homicides and suicides.  There are currently 25 states that allow permitless concealed carry of firearms.  All of this from a politicized reading of the archaic language of the Second Amendment. That alone would probably not be enough.  It also takes the fear tactic that the "government", "liberals", etc are "coming for your guns."  The reality is that there are so many weapons in the country - finding them and rounding them up would be an impossible task for anyone. And of course - nobody is interested in doing that. 

5:  Strengthening NATO.  The Biden administration has handled the crisis in Europe and rebuilding the NATO alliance expertly and they are not getting nearly enough credit. A secondary goal should be containing terrorism with our allies that comes in all forms including state terrorism that we are witnessing from Russia, North Korea, and Iran. It is likely there would be a much different outcome under a Trump administration.

5:  Nuclear non-proliferation: Every possible effort must be made to ensure that nuclear weapons are not used again.  There is too much loose talk about how limited tactical nuclear weapons would release less radiation and that a small local nuclear war would be "winnable" by somebody. Climate change should be a wake up call illustrating that even small changes in the environment can lead to catastrophic global changes. The detonation of nuclear weapons will not determine winners and losers. Mankind will lose and civilization will end.  

6:  Climate Activism:  As climate change gets more and more obvious the party that denied it was happening clearly has no solutions.  The infrastructure bill passed by the Biden administration was a major step in the right direction but even that is not enough. More changes need to follow to reduce carbon dioxide emissions and remove permanent environmental contaminants from the environment.

7:  Social programs.  There are Republican legislators who want to cancel Social Security and Medicare or euphemistically review it every 5 years and decide whether or not to cancel it.  Every person who has paid into those programs needs to be assured that they will get the agreed upon benefits.  Republicans use socialist rhetoric to impress upon their followers that the “socialists” want to take over the government and restrict their freedom.  In fact, social democracies are some of the fairest systems in the world and the United States has had social programs for a long time. Social programs in a democratic republic have nothing to so with a socialist government.

8:  Public health Initiatives: COVID-19 denialism was a major factor in unnecessary mortality and morbidity from that pandemic and there is no doubt who the most significant players in that denialism were. As the climate deteriorates and mankind is in closer proximity to millions of novel viruses in the wild – we need to infrastructure to assess those threats and either contain them or treat the outbreaks. We need people who understand science as a process and what needs to happen in this area.  Instead we have Republican politicians bragging about ignoring public health measures.

9:  A Coherent Immigration Policy:  Building walls and playing games with the lives of undocumented immigrants is not a coherent policy. It will take more comprehensive planning and aid to countries in Central and South America.  In addition the United States has a lower percentage of foreign born citizens than many European countries and Canada as well as a labor shortage so that increasing the number of legal immigrants each year can potentially decrease the number of people seeking political asylum. 

10:  Simplified Tax Policy:  Taxes are always a political football. Promise of no new taxes and tax cuts are not realistic, especially considering the current national debt.  A better plan is to make taxes more transparent and easier to complete. Business taxes should not be eliminated and should be consistent year-to-year and not a disincentive to doing business in the United States.

That is what I voted on.  It does not come down to a single issue for me.  It does not come down to voting for myths rather than reality.

But it does come down to a single party.

 

George Dawson, MD, DFAPA


Extremely relevant late breaking stories relevant to the above post:

1: Election deniers in Minnesota are training some election judges. Link - there are widespread efforts with various levels of organization by election deniers to interfere with the election process. This is a story from 2 days ago.

2:  What Fortune 500 Companies Said After Jan. 6 vs. What They Did.  Link - major US corporations said they would suspend political donations to election deniers and insurrectionists following January 6 - but those donations have resumed to the tune of $13 million.

3:  A message from Billie Eilish on the importance of voting. She describes the top issues highlighted above and I hope her followers and fans are able to follow through with her advice:  https://www.instagram.com/p/Ckj-ihtLw3G/?utm_source=ig_web_copy_link

4:  Charles Blow.  Dancing Near the Edge of a Lost Democracy.  New York Times November 6, 2022   https://www.nytimes.com/2022/11/06/opinion/midterms-democracy.html

"America is one bad election away from being a memory."

5:  Putin ally Yevgeny Prigozhin admits interfering in US elections.

They are obviously not interfering in the direction of more democracy.

6:  Bill Maher's analysis on the even of the election. Certainly hope he is wrong but if he isn't these are a few more reasons:

Democracy's Deathbed | Real Time with Bill Maher (HBO)

7:  Office of Intelligence and Analysis Operations in Portland April 20, 2021

Remember all of the reports about Antifa - the secret left wing terrorist organization that was supposed to be fighting the police and causing general unrest in the riots following George Floyd's death.  At the time is was pretty clear it was a myth to rationalize right wing militias showing up heavily armed to maintain law and order.  This mildly redacted report shows how US intelligence failed to show that any such organization existed.

8:  Democratic upset in U.S. midterms could roil markets, options mavens say

Nothing like last minute pro-GOP economic propaganda.  Three things:
1.  The current polls are based on the 1% of people using land lines who agree to take the poll.  With that level of sampling don't be too surprised if polls are wrong as they have been in the past.  There is no "upset" in that context only inaccurate polls.
2.  Why would the average voter be remotely interested in what "options mavens" have to say. Anyone who has followed financial news knows that it is often created to move markets in a favorable way and not to favor the casual investor or little guy
3.  See more objective data from the St. Louis FRED below.


Written by professional economists and not politicians.  Was this expansion due to another tech bubble?

"If this rise is driven by another asset bubble instead of the reasons mentioned above, then this trend is likely to cause another recession. Unfortunately, it is difficult to identify an asset bubble until after it has burst."

The current state of economics.

10:  Election workers brace for a torrent of threats: ‘I KNOW WHERE YOU SLEEP’:

And let's be honest - these threats are the direct result of the Big Lie, The Insurrection, and the fueling continued political violence by the GOP.  There are no Democrats threatening election workers.

11:  Voting Machine Problems in Arizona Fuel Right-Wing Fraud Claims

Trump spreads voter fraud claims on this election day, despite Republican official stating that there is no problem.

12:  John Oliver on Election Subversion:

13:  The gasoline price gambit:

Here is a link to a graph I just made on 12/6/2022 on crude oil prices per barrel versus gasoline prices per gallon.   The explanation of price volatility is in this post.  Don't let any politician from either party use these prices swings to suggest that somebody other than oil speculators and production companies are responsible.




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Monday, October 31, 2022

Incident Atrial Fibrillation and Intoxicants



I remain very interested in the cardiac and brain complications of medications and substances that are commonly used to get high or create altered states.  I am also very interested in the popular trend to characterize cannabis as some previously undiscovered medication that can cure everything ranging from anxiety to obstructive sleep apnea.  I was naturally interested when I saw this paper (1) looking at the issue of incident atrial fibrillation and common intoxicants.

The authors examine a very large database in California that included anyone who had been seen in an emergency department, ambulatory surgery center, or hospital over a period of 10 years (2005-2015).  After they eliminate minors, subjects with persistent atrial fibrillation, and subjects with missing data they had a total of 23,561,884 people. 998,747 of those people had incident atrial fibrillation (defined as the first encounter for atrial fibrillation).  Since their study design is a retrospective observational study they also recorded substance use was considered present if Substance use was considered present if there was coding for any indication of use of methamphetamine, cocaine, opiates, or cannabis.  Knowing the atrial fibrillation and substance use diagnoses – the authors calculate the hazard ratio for each of the substances of interest.

Hazard ratios are basically the ratio of the people exposed to intoxicants who developed atrial fibrillation over the unexposed who developed atrial fibrillation.  So any number greater than 1 means that the population exposed to intoxicants had greater risk.  The corrected hazard ratios were noted to be 1.86 (methamphetamine), 1.74 (opioids), 1.61 (cocaine), and 1.35 cannabis. The authors adjusted for common atrial fibrillation risk factors and ran an additional negative control analysis and looked at the scatter of data pints for these 4 substances and hazard ratios of developing appendicitis, connective and soft tissue sarcoma, and renal cell carcinoma and showed no consistent pattern for these illnesses.

There are a couple of interesting considerations relevant to this study.  The first is the mechanism of action in each case. With stimulants there is a direct hyperadrenergic effects and depending on the individual and dose of the drug varying degrees of tachycardia, palpitations, and hypertension.  Long term users frequently end up with cardiomyopathy from these effects and in some cases ventricular arrhythmias and congestive heart failure. There can also be acute vascular effects like ischemia either due to the increased cardiac demand or pre-existing arteriosclerosis. Atrial fibrillation has not typically been placed in that group of morbidities from stimulant use. Patient with atrial fibrillation often notice emotional precipitants for discrete episodes or atrial fibrillation although a recent study showed that the only reliable precipitant was alcohol use (2). There were significant limitations with that study with attrition and length of the study although I generally agree that alcohol is a clear participant.  Precipitants need to be carefully approached and I suspect that attentive physicians have noted variable phenomenology on an individual basis. 

The high hazard ratio for opioids is a little puzzling. Hyperadrenergic states can occur with the euphorigenic effects and withdrawal effects as well. Direct comparison with stimulants may be difficult due to rapid dose escalation and some degree of tachyphylaxis.  Cannabis is not surprising to me at all. Many initial cannabis smokers notice that their heart is pounding and don’t know why.  They find it unexpected given the conventional wisdom that cannabis is supposed to be a benign substance. Many initial users also get increased anxiety and, in some cases, have a panic attack that may be due to the cardiac sensations. The primary heart pounding sensation is because cannabis causes hypotension and they are experiencing reflex tachycardia. The effects may be less predictable because cannabis use can affect both sympathetic and parasympathetic pathways that can potentiate arrhythmias. A case report of cannabis induced atrial flutter (3) was described as occurring in a woman with a history of hypertension that eventually had to be terminated by an intravenous antiarrhythmic.   

Atrial fibrillation and other cardiac arrhythmias are another good reason for avoiding intoxicants including alcohol (in the supplementary analysis alcohol had a Hazard Ratio of 2.37).  It could be argued that it is basically a numbers game – since most people who use these intoxicants do not develop incident atrial fibrillation.  As of this moment, even if you have had your DNA analyzed for what are known about atrial fibrillation genes – you can’t be certain that you are not susceptible to the problem. And as outlined above there are many additional cardiac problems and that are possible from using these compounds.  The safest path is to avoid these intoxicants all together.

 

George Dawson, MD, DFAPA

 

 

References:

1:  Lin AL, Nah G, Tang JJ, Vittinghoff E, Dewland TA, Marcus GM. Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation. Eur Heart J. 2022 Oct 18:ehac558. doi: 10.1093/eurheartj/ehac558. Epub ahead of print. PMID: 36257330.

2: Marcus GM, Modrow MF, Schmid CH, Sigona K, Nah G, Yang J, Chu TC, Joyce S, Gettabecha S, Ogomori K, Yang V, Butcher X, Hills MT, McCall D, Sciarappa K, Sim I, Pletcher MJ, Olgin JE. Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial. JAMA Cardiol. 2022 Feb 1;7(2):167-174. doi: 10.1001/jamacardio.2021.5010. PMID: 34775507; PMCID: PMC8591553.

3: Fisher BA, Ghuran A, Vadamalai V, Antonios TF. Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. Emerg Med J. 2005 Sep;22(9):679-80. doi: 10.1136/emj.2004.014969. PMID: 16113206; PMCID: PMC1726916. [full text] 

Wednesday, October 19, 2022

Abstract Attack Journal Article Presentation Format

 

I recently participated in an Addiction Medicine Journal Club where the presenter used a novel presentation technique called Abstract Attack. The result in terms of group process was so good – I thought I would present it here for further exposure and comment.  As a qualifier I would add that I have not spoken directly to the creators and base this post on my direct participation in the format and the PowerPoint from the creators (1) and the presentation I attended (2).

Standard presentations in medicine and other academic fields typically consist of a single presenter charged with presenting data or techniques for information and some discussion.  The expertise of the presenter and role of the audience varies considerably.  For example, in my Biochemistry course in medical school the seminars were focused on techniques and concepts. The course instructor would typically choose a paper or two on a clear topic like diphtheria or cholera toxin.  The presenter was responsible for presenting those two papers at the minimum with additional papers as necessary. That was in 1978 – well before the Internet and online resources. All papers had to be obtained as hard copies from the medical library.  We would have two or three biochem seminars per week – so there were always a number of presentations to prepare for and the information content was variable.  My pharmacology course used a similar format but slide presentations were allowed. Since there was no digital presentation software – the slides had to all be shot on 35 mm film and projected.  That was the standard until well after I completed residency and started working. Eventually presentation software was developed making the job much easier.

Microsoft PowerPoint eventually evolved into the standard presentation format but it is not without controversy.  In the past 15 years there have been numerous presentations and papers written about everything that people consider to be wrong with PowerPoint.  That criticism is highly variable such as too little to too much information, being more boring that an extemporaneous lecture, problematic graphics and format on the slides, reading the slides, and competing software that claims to produce a better presentation.  The competition angle is an interesting one because in the beginning I bet on (and paid for) two competing products before it became apparent that PowerPoint would be the winner. It is difficult to win against a product that is installed on most business computers in the country.

My person bias is that I like the PowerPoint format.  The product is greatly improved in the past decade and can also be used to produce graphics for other applications.  I have attended seminars and courses on this to improve the approach with PowerPoint from a graphical standpoint and my slide making has improved considerably. I think it is very useful to put up graphics and texts that provide more information to the audience while I am free associating to the slides. To me the main difference between a verbal only lecture and a PowerPoint presentation is the greater informational content.  Consider that TED Talks are supposed to present a great idea in 18 minutes.  I am supposed to be presenting many ideas and facts in 50-50 minutes. That is what a PowerPoint presentation is for.

The doesn’t mean that all high information PowerPoints are successful. The speaker still has to be fairly good in both presentation style and engaging the audience. The audience has to be well behaved and focused on the content. I was giving a fairly detailed lecture on alcohol use and the latest World Health Organization (WHO) report on the scope of the problem.  There was a student in the audience checking the data on my slides (taken directly from the report) about what he could find on his phone and arguing about it. There are always unexplained emotional reactions in the crowd and in some cases, people get up and leave – even when nothing presented is really controversial. We have all attended presentations when the discussion starts with the dreaded: “I don’t have a question but I would like to comment……” followed by a 10 minute long irrelevant digression.  

When you experience all of those occurrences at conferences and lectures, you can’t help thinking: “Is there a better way to keep all of this on track?” Limiting the discussion, not taking questions, or having all of the questions submitted and moderated are certainly possibilities that I have seen used successfully. But I was recently exposed to a presentation format that structured the responses right in PowerPoint and that led to a focused high-quality discussion.  I will explain the format and hopefully provide a good example of how to approach the problem.

The method is called Abstract Attack and it was apparently devised by members of the University of Minnesota North Memorial Family Medicine Program.  Rene Crichlow, MD, FAAFP is credited with the concept and in the PowerPoint I acquired her co-presenters were Tanner Nissly, DO, and Jason Ricco, MD, MPH (1).  I first experienced this approach in a journal club teleconference (2) that was presented by Ian Latham, MD a resident from the UMN program on an article about lorazepam versus phenobarbital for alcohol detoxification based on a 2021 paper (3).

The overall goals for this presentation format are from family practice curriculum.  In the initial presentation the authors use the Accreditation Council for Graduate Medical Education (ACGME) requirements for scholarship to develop the Abstract Attack approach.  Those scholarship requirements can be found in the document on common requirements for all residency programs. Interested readers can find the specifics in a box graphic on page 26 of this document.  It is an elaboration of the way all physicians are trained to critique scientific and clinical studies and the application of the studies to clinical work.  The primary goals of Abstract Attack (1) are cited as:

1.  "Abstract Attack", a method to provide uniform acquisition of skills and knowledge

2.  Sufficient for a practicing clinician to confidently, participate in efficient and effective Evidence Based critique of the medical literature at the point of care

 The secondary goal is “Eschew Obfuscation”.

The overall process is described as patient rather than disease oriented and adhering to a critical appraisal pathway that answers the questions:   Pertinent to your patients’ care?  Consistent or Inconsistent?  Valid or Invalid?  The structured order of presentation is given in the slide below:


  

In the session I attended (2) the author discussed the overall goal of being able to present journal articles with the assumption that nobody else has read it.  He proceeded to illustrate how the presented information could be discussed at the level of every slide by the following prompts (that he incorporated in every slide):

What is interesting about this?

What is concerning about this?

What do I need to know more about?


I will illustrate with a few slides from a recent JAMA paper (5).  The slides cueing the discussion might look something like this.





   


Additional slides are provided on the methods and results.  That is followed by a slide with questions exploring how the study potentially impacts clinical practice and what additional information or studies may be needed.  Supplemental slides can contain information on the scientific and statistical concepts used in the paper.  The emphasis is clearly proceeding from the clinical trials to clinical practice.

My direct experience with this format is that there was timely discussion every step of the way.  Senior clinicians and physicians can add commentary early in the process about what they see are being important about the study.  The audience is clearly engaged without every reading the paper. The presenter can add critical information in supplementary slides at the end after the discussion on how impactful the information is on clinical practice and what else might be needed.

Overall, I thought this was a breakthrough in how to make these presentations efficiently when everyone’s time is at a premium. Dr. Crichlow and her colleagues are to be congratulated.  I have made a comparison slide below.



 

George Dawson, MD, DFAPA

 

References:

1:  Crichlow R, Nissly T, Ricco J.  Trans-formative Journal Club Experience as a Basis for a Longitudinal EBM Curriculum.  PowerPoint Presentation.  Accessed on October 16, 2022.

2:  Latham I. Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study Addiction Medicine Journal Club.  PowerPoint Presentation. August 2, 2022.

3:  Hawa F, Gilbert L, Gilbert B, Hereford V, Hawa A, Al Hillan A, Weiner M, Albright J, Scheidel C, Al-Sous O. Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study. Cureus. 2021 Feb 11;13(2):e13282. doi: 10.7759/cureus.13282. PMID: 33728215; PMCID: PMC7949711.

4:  Accreditation Council for Graduate Medical Education (ACGME).  Common Requirements Currently In Effect.  7/1/2022:  https://www.acgme.org/what-we-do/accreditation/common-program-requirements/  Accessed on 10/19/2022.

5:  Florian J, van der Schrier R, Gershuny V, Davis MC, Wang C, Han X, Burkhart K, Prentice K, Shah A, Racz R, Patel V, Matta M, Ismaiel OA, Weaver J, Boughner R, Ford K, Rouse R, Stone M, Sanabria C, Dahan A, Strauss DG. Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial. JAMA. 2022 Oct 11;328(14):1405-1414. doi: 10.1001/jama.2022.17735. PMID: 36219407.


Supplementary Info:

Any slide above can be enlarged by clicking on it.

 


Saturday, October 8, 2022

Minnesota Medical Cannabis Program Petitions

 



I have written about this program in the past.  In Minnesota, we have a medical cannabis program that allows for the prescription of specific forms of cannabis for a list of what are seen as indications.  To get on that list is basically a review of opinions and the Commissioner. Even though this program runs like a mini-FDA, it does not have a standard for approving conditions for medical cannabis use.  And let’s face it - that is because the supporting evidence for using medical cannabis is very weak and in many if not most instances – non-existent. And as I have pointed out in the past – the evidence collected by the program is also weak.  As far as I know the program does not produce any detailed adverse drug effect information and a lot of that advice depends on the pharmacists dispensing the medical cannabis.

This year the conditions up for placement on the list of indications include opioid use disorder, obsessive compulsive disorder, and irritable bowel syndrome. I restricted my comments to the first two conditions and the rationale is very clear. In the case of opioid use disorder (OUD), it is a widespread drug epidemic at this point fueled by widespread availability of opioids and synthetic opioids. Even though physician prescriptions have decreased overdose deaths continue to increase on a year-to-year basis. The pattern of overdoses has also changed substantially since OUD has spread from metropolitan to rural areas. Thirty years ago, OUD and overdose deaths were practically unheard of in rural areas and now they are commonplace. There are effective treatment for OUD as listed in the letter that follows.  There is a problem with access to substance use disorder treatment.  Most states have practically no detoxification facilities.  Access to physicians who are prescribing medication assisted treatment (MAT) for OUD (MOUD) is also very limited.

Like most political movements in the country – there is no critical analysis of the various cannabis initiatives.  To me – it was obvious from the start that medical cannabis was a way to start building political consensus for legalization of cannabis. Adding more intoxicants to the environment is never a good idea – but the practical issue is that the lesson of alcohol prohibition was that it could not be done without increasing crime, corruption, and the health dangers of unregulated alcohol. So a medical cannabis initiative is really not a genuine attempt to treat medical conditions with cannabis.

On that basis – it is not surprising that there is significant overreach in finding conditions where medical cannabis can be used. OUD and OCD are just two more diagnoses on that list. I was informed that my comments will be added but the vast majority of comments are not by physicians and are basically testimonials to cannabis. The FDA receives a lot of criticism and they also elicit public commentary but there is a core body of scientific decision makers.

With the writing of this post President Biden just came out with a statement that he is going to pardon people who are incarcerated for simple possession of marijuana and encourage governors to do the same (1).  That may be easier said than done since there was also a news report that the majority of these people have additional complicating charges.  He also initiated a review process by Secretary of Health and Human Services and the Attorney General on the way marijuana is listed in the Control Substance Act schedule.  It is currently a Schedule I drug making it the most dangerous and without medical applications according to this ranking. That results in a large grey zone when it is legally prescribed in some states and approved for recreation use in others.  There are associated problems with banking due to the federal scheduling but in an election year when any number of people from both parties are tripping over each other to legalize it – it seems like a foregone conclusion that it will be rescheduled at the minimum.

The Minnesota legislature approved low dose cannabis edibles earlier this year. There is a question about whether that was done by mistake. This is another step toward the eventual legalization of cannabis in Minnesota and will probably lead to the extinction of the Medical Cannabis program.  This story also illustrates the confusion among legislators about the basic differences between raw materials and cannabinoid derivatives. My viewpoint is legalization of cannabis was the goal all along and the users of medical cannabis have objected to higher fees for the medical product and many prefer smoking cannabis rather than using other forms.

 

George Dawson, MD, DFAPA

 

1:  Statement from President Biden on Marijuana Reform October 7, 2022 Link.

2:  Miranda S.  Minnesota lawmakers voted to legalize THC edibles. Some did it accidentally.  July 2, 2022 Link.


The letter not in support of indications for opioid use disorder or obsessive compulsive disorder:

October 3, 2022

Office of Medical Cannabis
PO Box 64882
St. Paul, MN 55164-0882

To Whom It May Concern:

I am a Minnesota psychiatrist who recently retired from clinical practice. I continue to research and write about psychiatry.  I worked at one of the largest substance use disorder treatment facilities in the United States. Every person I saw had a substance use disorder (SUD) that was significant enough to need residential treatment. Alcohol use disorder was the most common followed by opioid use disorder (OUD).  I was also an adjunct professor and lectured on the epidemiology, assessment, and treatment of substance use disorders. Areas of focus included the neurobiology of SUD, opioid use disorders, chronic pain, and Attention Deficit~Hyperactivity Disorder. I did research on medication assisted treatment of alcohol use disorder and depression. 

As an SUD develops, there are several associated biases that lead to chronicity. The first is the euphorigenic effect or “high” that occurs with all substances. That becomes a permanent memory that all subsequent episodes of use are compared against. Tolerance to drug effects limits the ability to experience that same degree of euphoria.  That leads to attempts to use more or more powerful versions of the same drug. In the case of OUD, that has led to the use of more powerful opioids like fentanyl. A second bias is the idea that all emotions and reactions to stress can be controlled by external substances.  Cannabis, alcohol, and benzodiazepines are used for that purpose. In that situation, withdrawal symptoms are misinterpreted as anxiety or depression.   That leads to an additional substance being taken. Detoxification is required to determine a person’s baseline state and whether there is a treatable anxiety or depressive disorder. A third bias is that “I have a lot of time to quit.” Young people with severe SUD will often tell themselves: “I am only in my 20s, I can quit later and at that time go to work or school.” That prolongs their risk exposure and the associated morbidity and mortality. A fourth bias is people with SUD are not risk averse. In other words, if they knew a substance contained fentanyl and were risk averse, they would avoid it. This is not true. Many will seek out fentanyl products or products they know contain fentanyl in pursuit of getting high. That pursuit can get to the point that greater amounts of substances or more novel substances are used and they do not care what the outcome is. They are willing to risk a fatal outcome in pursuit of getting high.  Finally, withdrawal symptoms from substances create a negative reinforcement bias – substances need to be taken to avoid withdrawal symptoms.

Easy access to opioids is a major factor in the continuing opioid crisis and the “three waves” of this epidemic that are described by the CDC (1). There were several papers (3) published that suggested that medical cannabis use was associated with less opioid use. Those findings have not been validated over time.   There has been a study done showing that opioid use was more likely to increase rather than decrease (4) with cannabis use. That study is consistent with what I have seen in the clinic.  

To summarize:

1.  We are still in the midst of a 2 decades long opioid use epidemic that has produced significant overdose mortality and morbidity. 

2.  There are current FDA approved treatments (10 drugs in 3 categories) that have demonstrated ability to prevent opioid overdoses and treat opioid use disorder (2). 

3.  Suggesting that Minnesota residents with an opioid use disorder use cannabis with no proven treatment efficacy over the FDA approved medications that have efficacy presents a clear ethical problem considering the level of mortality associated with this disorder.

For these reasons medical cannabis should not be approved for opioid use disorder.

I am also recommending that medical cannabis not be approved for the treatment of obsessive-compulsive disorder. The bulk of my argument rests on the information that I submitted last year recommending no medical cannabis approval for generalized anxiety disorder. In that submission, I pointed out that for many people cannabis use leads to anxiety and panic attacks rather than alleviating them. Obsessive-compulsive disorder (OCD) has effective psychotherapies and medical therapies. In fact, psychotherapy is the primary treatment modality. We currently have a healthcare system that rations access to both psychotherapy and medical treatment. When the lack of clinical trials of cannabis in OCD is considered, the same ethical dilemma presents as in the case of opioid use disorder. Is cannabis approved for OCD because health care systems and government regulators refuse to provide access to proven methods of treatment?

In both the case of opioid use disorder and obsessive-compulsive disorder, neither should be an indication for medical cannabis for the above stated reasons.

Sincerely,

George Dawson, MD, DFAPA

Lino Lakes, MN

 

 

References:

1:  CDC.  Understanding the Epidemic:

https://www.cdc.gov/opioids/basics/epidemic.html

 

2:  FDA Information about Medication-Assisted Treatment (MAT):  https://www.fda.gov/drugs/information-drug-class/information-about-medication-assisted-treatment-mat

3. Bachhuber MA, Saloner B, Cunningham CO, et al. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999–2010. JAMA Intern Med. 2014;174:1668–1673.

4:  Olfson M, Wall MM, Liu SM, Blanco C. Cannabis Use and Risk of Prescription Opioid Use Disorder in the United States. Am J Psychiatry. 2018 Jan 1;175(1):47-53. doi: 10.1176/appi.ajp.2017.17040413. Epub 2017 Sep 26.

 


Thursday, September 29, 2022

Emotional Blunting By Antidepressants - Does It Occur?

 


Ron Pies and I reviewed three recent papers on emotional blunting in this paper called Antidepressants Do Not Work by Numbing Emotions. It is a very self-explanatory essay that I encourage anyone to read if they have an interest in that topic specifically or in the general repetitive criticism that only our field seems to enjoy. I have previously commented on the rhetorical aspects to a previous paper and recent publications allow us to address specific scientific issues. The main argument that emotional blunting is the mechanism by which antidepressants work - has no scientific merit as explained in the essay. The basic argument is that if emotional blunting is rated at baseline before any antidepressants are started it is present and as treatment begins and starts to work – emotional blunting decreases as the depression remits. That led the authors we reviewed to conclude it was more likely a symptom of depression than either a mechanism of action or a side effect.

 1:  Measurement – is a better measurement needed?

In the reviewed studies we made some specific comments on the methodologies used to detect emotional blunting specifically Item 8 of the Montgomery Ã…sberg Depression Rating Scale (MADRS) or the Oxford Depression Questionnaire (ODQ). The ODQ was previously the Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQESA or OQuESA).

The single item on the MADRS provides the most unbiased assessment of emotional blunting and is a single question worded very much like a clinician might ask to assess the problem. The ODQ has more questions and a specific question where the subject is asked to estimate whether or not the antidepressant is contributing to antidepressant side effects.  Since no other potential etiologies (like depression) were considered we thought that these were questions that might lead to predictable biases like choosing antidepressants as the cause of decreased emotional range rather than the depression.

Are there better questionnaire designs to eliminate bias and allow for quantification.  Two good examples include the Attributional Style Questionnaire (ASQ) (1) and the Cognitive Style Questionnaire (CSQ) (2). In both of these questionnaires - subjects are asked in an open format to write down what they consider to be the cause of a hypothetical situation, answer a question about that situation, and then rate the important of the cause. The questions are all focused on perceived internal and external causes of depression consistent with the cognitive theory of depression. There is no reason why a similar questionnaire could not be designed to find cognitive and emotional side effects of medications.  It could be validated by including questions about the known physical side effects of medication.    

2:  Normal subjects taking antidepressants:

In thinking about unbiased opinions about the emotional effects of antidepressants my mind wandered back to a paper I read in the American Journal of Psychiatry many years ago.  It was easy to remember because it involved giving fluoxetine to research subjects who had no known psychiatric diagnoses. In that study – 15 subjects were enrolled and took placebo for two weeks followed by fluoxetine 10 mg x 1 week then fluoxetine 20 mg/day x 5 weeks and then placebo daily for two weeks.  There were assessed weekly on standard scales for anxiety and depression.  They were also assessed weekly on the General Well Being Schedule and the Quality of Life Enjoyment and Satisfaction Questionnaire.  Subjects were also assessed weekly for side effects and only three of the 15 subjects reported side effects and they were nausea, dyspepsia, and dizziness – all typical SSRI side effects.  The authors conclude:

“No significant effects attributable to fluoxetine were observed on any of the psychological variables examined. Minimal adverse effects were reported. … Significant mood elevating and other psychological effects of fluoxetine would appear to be induced only when symptomatic targets exist.”

Interestingly these authors contrast their work with that of Peter Kramer (4) and suggest that: “….mood-enhancing and other psychoactive effects of SSRIs are not a general property of these agents but are manifest in the context of target symptoms.”  A similar argument has been made about emotional blunting and why it may not occur in normal subjects.

In a second study of fluoxetine and dothiepin in subjects without mental illness a 5 week placebo controlled, double blind crossover study was used (4).  Each subject received each treatment and placebo.  The active treatment lasted for 35 days. Subjects received fluoxetine 20 mg/day or dothiepin (a tricyclic antidepressant) titrated to 150 mg/day. They were tested at day 10 and day 36.  Eleven mood ratings using an analogue scale were done three times a day. The subjects were also asked is they had any “problems with your health”.  Some increased irritability (3 subjects), anxiety (one subject), and “mood lowering” (2 subjects) was noted.  There were no reports of emotional blunting. The researchers generally reported:

“Throughout the study period, all subjects remained well, including during the drug-free periods between treatments.”

In looking for a third study, I found one by David Healy – a well-known pharmaceutical business critic (6).  This study involved 20 subjects randomized to receive 2 weeks of either reboxetine or sertraline in a cross over design.  There was an option to increase either drug to the next expected level on day 5 of active drug treatment.  Three scales were done on a daily basis including the Profile Of Mood States (POMS), Positive and Negative Affect Scale (PANAS), and the Social Adaptation Self Evaluation Scale (SASS).  A side effects questionnaire was administered. Subjects were also asked if they could distinguish the “behavioral effects” of the drugs and to rate their preferences on an 11 point Likert scale ranging from “worse than normal (-5) to better than normal (+5).  A relevant excerpt from this paper:

“In focus group settings, while still under the blind, half of the subjects volunteered that sertraline made them mellow, or less emotionally reactive and that these effects were either appreciated or not, while yet others described agitation. Effects consistent with a reduction in emotional reactivity were not described with reboxetine.”

This focus group observation was not observed in any of the data collected from the mood rating scales.  The authors point out studies suggesting that normal volunteers do not tolerate medications well and suggest that their study shows that tolerance of the antidepressant may depend on whether it is a preferred agent of the subject.  Side effects listed but not quantitated include chilblains, sweats, insomnia, nausea, sexual dysfunction, and “jaw or throat dyskinesias or dystonias on sertraline.”

In summary, my main additional concerns about the emotional blunting issue and whether it occurs to any extent with antidepressants is one of accuracy of measurement and why it has been conspicuously absent in clinical trials until recently – including trials where antidepressants are given to normal controls (defined as volunteers screened for the presence of any current or lifetime psychiatric disorders).  Although I suggested a way to get to a much less biased measurement of emotional blunting, I have a question about whether it can be accurately measured at all in an era where psychiatric research is often presented as political debate in social media and the popular press. There have been many examples of how biased press coverage has misrepresented the effects of psychiatric medications and you only have to look as far as the Peter Kramer reference and the appendix on “Violence”.  A study to look at a better questionnaire to see if this is ever spontaneously mentioned when it is not cued would be useful - but it is probably not any more possible today than asking if the last election was stolen. 

On the issue of emotional blunting in clinical practice – I have seen the equivalent in some patients over the years. I typically discuss it with people as restricted affective range that either they notice or other people notice. It typically occurs during reassessments of people who have partially remitted depressions. At that point in time, it makes sense to discuss the time course of that phenomenon and try to determine the time course and whether it is improving or getting worse. After making it explicit at that point – the options in clinical care include continued observation or an immediate change to a different medication. That aspect of clinical care would be an interesting study in itself – because in my experience the majority of people do not want to change the medication at that initial discussion. I think it is also an element of ongoing informed consent at that point.

At a practical level, I think that the study by Peters, Balbuena, and Lodhi (7) that we referenced has paved the way for many more replication studies for any RCTs of antidepressants that used the Montgomery-Ã…sberg Depression Rating Scale (MADRS) and that is a very significant number.

It also requires a degree of biological sophistication to realize that brain systems are so complex and individualized that you cannot expect a medication to affect everyone in the exact same way – either positively or negatively. In fact, you cannot have that expectation in attempting to treat far less complex organ systems. Responses to treatment and side effects in medicine are always probability statements.


George Dawson, MD, DFAPA

 

References:

1. Peterson C, Semmel A, Von Baeyer C, Abramson LY, Metalsky GI, Seligman ME. The attributional style questionnaire. Cognitive therapy and research. 1982 Sep;6(3):287-99.

2.  Haeffel GJ, Gibb BE, Metalsky GI, Alloy LB, Abramson LY, Hankin BL, Joiner Jr TE, Swendsen JD. Measuring cognitive vulnerability to depression: Development and validation of the cognitive style questionnaire. Clinical Psychology Review. 2008 Jun 1;28(5):824-36

3.  Gelfin Y, Gorfine M, Lerer B. Effect of clinical doses of fluoxetine on psychological variables in healthy volunteers. Am J Psychiatry. 1998 Feb;155(2):290-2. doi: 10.1176/ajp.155.2.290. PMID: 9464215.

4. Kramer PD: Listening to Prozac. New York, Penguin, 1993

5.  Wilson SJ, Bailey JE, Alford C, Weinstein A, Nutt DJ. Effects of 5 weeks of administration of fluoxetine and dothiepin in normal volunteers on sleep, daytime sedation, psychomotor performance and mood. J Psychopharmacol. 2002 Dec;16(4):321-31. doi: 10.1177/026988110201600406. PMID: 12503831.

6.  Tranter R, Healy H, Cattell D, Healy D. Functional effects of agents differentially selective to noradrenergic or serotonergic systems. Psychol Med. 2002 Apr;32(3):517-24. doi: 10.1017/s0033291701005086. PMID: 11989996.

7.  Peters EM, Balbuena L, Lodhi RJ. Emotional blunting with bupropion and serotonin reuptake inhibitors in three randomized controlled trials for acute major depressive disorder. J Affect Disord. 2022 Dec 1;318:29-32. doi: 10.1016/j.jad.2022.08.066. Epub 2022 Aug 24. PMID: 36029876.

8.  Hieronymus F, Lisinski A, Østergaard SD, Eriksson E. The response pattern to SSRIs as assessed by the Montgomery-Ã…sberg Depression Rating Scale: a patient-level meta-analysis. World Psychiatry. 2022 Oct;21(3):472-473. doi: 10.1002/wps.21029. PMID: 36073711; PMCID: PMC9453909.


Supplementary:

I was made aware of a new analysis of MADRS data (8) today after writing the above essay.  Those authors analyzed MADRS ratings from 4,243 subjects participating in twelve acute phase placebo‐controlled trials of an SSRI in major depression and looked at emotional blunting on Item 8 of the scale. They found that treatment reduced emotional blunting with the same effect size as other items on the scale.  They agree with the opinion that emotional blunting should not be ignored but in the case of these antidepressant trials the ratings moved in a favorable direction.

Updated Table including this new analysis (click to see a clearer version):



Graphic Credit:

Nasa surface of Europa per their media guidelines