Expanding Beyond Traditional Lipid Markers

While LDL cholesterol remains a crucial target in cardiovascular prevention, Dr. Natarajan highlighted the importance of looking beyond this traditional marker. He emphasised the value of measuring ApoB, which provides a more accurate count of atherogenic particles and can be particularly useful in patients with features of insulin resistance.

Dr. Natarajan suggests aiming for an ApoB level about 10% lower than the LDL cholesterol target. He explained, “If we’re aiming for about 40 [mg/dL for LDL], that’s like 36 [mg/dL for ApoB], so relatively similar. If it’s not and it’s higher, then obviously increase the LDL cholesterol-lowering medicines because lower the ApoB and then follow the ApoB with the lipids going forward.”

The Role of Inflammation in Heart Disease

The conversation touched on the often-overlooked role of inflammation in cardiovascular disease. Dr. Natarajan discussed the CANTOS trial, which demonstrated that targeting inflammation with canakinumab, an IL-1β antibody, could reduce cardiovascular events. He also mentioned the potential of colchicine, an inexpensive anti-inflammatory drug, in secondary prevention of cardiovascular events.

Regarding colchicine, Dr. Natarajan stated, “I do really think about it particularly for patients who have had recurrent events. The people who market the medicine and do research do remind us that C-reactive protein was not required in the inclusion, but nobody has done that secondary assessment to see if measuring C-reactive protein would be helpful in identifying the beneficial patients.”

Clonal Hematopoiesis of Indeterminate Potential (CHIP)

Dr. Natarajan, a leader in CHIP research, explained how these acquired mutations in blood stem cells can significantly increase cardiovascular risk. Despite strong evidence linking CHIP to adverse cardiovascular outcomes, routine testing is not yet implemented due to cost and insurance considerations.

He noted the potential for future screening: “There are research tests that are kind of in the $10 to $20 range right now for CHIP. And if flipped over to the clinical side will also be reasonably low cost. And so, for the paradigm for clinical implementation, that cost part is necessary.”

The Promise of Polygenic Risk Scores

Both doctors expressed frustration at the slow adoption of polygenic risk scores (PRS) in clinical practice. These scores, derived from hundreds of genetic variants, can identify individuals at high risk for coronary artery disease much earlier than traditional risk factors.

Dr Natarajan emphasised the potential impact: “By polygenic risk score, you can find 1 in 5 individuals with that same risk [as familial hypercholesterolemia]. If you go higher than that, it’ll be even higher risk related to that. And that is noble information very early in life.”

Emerging Drug Classes: GLP-1 Agonists and SGLT2 Inhibitors

The podcast highlighted the expanding role of drugs originally developed for diabetes in cardiovascular prevention. GLP-1 receptor agonists have shown remarkable benefits in weight loss and cardiovascular outcomes, while SGLT2 inhibitors have proven effective in heart failure management, particularly in patients with preserved ejection fraction.

Dr Natarajan expressed enthusiasm about these developments: “I feel like every week I’m reading a new clinical trial about a new clinical outcome benefit as it relates to GLP-1 receptor agonists… The fact that we have medicines that are safe and effective for lowering weight that also have real strong effects on clinical outcomes is tremendous.”

Looking to the Future

Dr. Natarajan emphasised the need for continued innovation in cardiovascular prevention. He pointed out that as traditional risk factors are better managed, new factors like insulin resistance and obesity are becoming increasingly important.

Reflecting on the future, he said, “There is a dramatic potential for these kinds of therapies in reducing the residual risks that we see related to cardiovascular disease. So I’m enthusiastic and excited. I think a lot more biology needs to be understood of how much of this is being influenced specifically through this pathway versus a very effective weight loss medicine.”

In conclusion, the conversation between Dr. Topol and Dr. Natarajan painted a picture of a field on the cusp of significant advancements. The tools for preventing cardiovascular disease are expanding rapidly, from novel biomarkers and genetic risk assessment to innovative drug therapies. However, the challenge remains in translating these scientific advancements into widespread clinical practice, particularly in healthcare systems not optimised for preventive care.

The post The Future of Cardiovascular Disease Prevention: Insights from Drs. Eric Topol and Pradeep Natarajan appeared first on Medika Life.

This essay will briefly explore this hypothesis-generating finding.

Speaking to Helio, study author Sage E. Eiset offers this take:

“The hypothesis is not new but has not yet been investigated in a population-based setting. In Denmark, we have several population-based registries with many years of high-quality data, including a public dental registry. This was a unique opportunity to investigate the tooth agenesis–cancer hypothesis.”

Let’s look at the new and provocative study.

Background

Tooth loss is a common condition that affects millions of people around the world, and cancer is a major health concern that affects millions of people each year.

Previous research has suggested a link between missing teeth from birth and cancer risk, but this link has not yet been thoroughly investigated in a population-based setting.

A new study from Denmark builds on previous research to shed new light on the potential link between missing teeth at birth and cancer risk.

Study Details

Researchers in Denmark looked at records of people born between 1977 and 2018 to see if there was a link between missing teeth at birth and certain types of cancer.

The idea is brilliant.

They collected information from various databases on missing teeth (excluding wisdom teeth) and cancer diagnoses.

The study involved over 2.5 million individuals, with just over 2.8 percent having missing teeth at birth and 1.1 percent being diagnosed with cancer at a young age.

Out of those, 778 people had both missing teeth at birth and cancer.

Study Results: Surprising Connection Found: Missing Teeth At Birth Linked to Cancer Risk

The study found that children aged 1 to 3 years with missing teeth at birth were more likely to develop certain cancers, including the following types:

• leukemia (a type known as acute myeloid leukemia; 3.5 times higher risk)
• neuroblastoma (4.2 times)
• kidney tumors (4.6 times)
• liver cancer (7.1 times)
• muscle cancer (8.8 times)

Children aged 3 to 6.

Children aged 3 to 6 had a higher risk of muscle cancer (rhabdomyosarcoma risk increased 3.5 times) and leukemia (acute myeloid leukemia risk increased 3.8 times).

Children aged 10 to 20.

Between 10 to 20 years old, individuals with missing teeth had an increased bone cancer risk. Osteosarcoma, a type of bone cancer, risk increased by 2.2 times.

Children aged 20 and older.

Finally, young adults aged 20 to 30 had a higher chance of developing appendix (2.5 times) and bladder cancers (3.4 times), while those aged 30 to 40 had a 2.8-fold increase in colorectal cancer risk.

My Take

Do you have a missing tooth (tooth agenesis)?

Tooth agenesis is quite common. On the other hand, the study revealed few cancer cases.

Even if your risk is up to 8.8 times higher for muscle cancer, it is very unlikely you will ever get it.

There are only 400 to 500 children who develop muscle cancer each year.

Why Is There a Tooth Agenesis: Cancer Connection?

The findings may be erroneous; that is, they occurred by chance.
Still, some findings are biologically explainable.

Did you know tooth development is a complex process involving several signaling pathways? Fascinating, right?

These pathways include Wnt, BMP, FGF, Shh, Eda, and others. It’s amazing how many intricate mechanisms are at play to give us our pearly whites!

For example, the AXIN2 gene is connected to tooth anomalies and colon cancer.

Limitations of the Study

The study is registration-based.

While this approach allowed the researchers to build a massive database, it did not allow the establishment of causality.

The findings may be erroneous; that is, they occurred by chance.

Finally, if a very young child had previous cancer therapy, that could impact oral health.

Takeaway Message — Surprising Connection Found: Missing Teeth At Birth Linked to Cancer Risk

A recent study from Denmark found that missing teeth (excluding wisdom teeth) at birth may be linked to an increased risk of certain cancers.

The study, which involved over 2.5 million individuals, found that children aged 1 to 3 years with missing teeth were more likely to develop acute myeloid leukemia, neuroblastoma, kidney tumors, liver cancer, and muscle cancer.

While the study suggests a possible link between missing teeth and cancer risk, it is important to note that the overall risk of developing these cancers is still quite low.

The post Surprising Connection Found: Missing Teeth At Birth Linked to Cancer Risk appeared first on Medika Life.

I’d be remiss not to point out that Medscape, in this context, is merely reporting medical news. Their article centers around a new analysis, drawn from the Columbia Mass Murder Database (CMMD), which suggests that mental illness is incidental in mass shootings.

“People with serious mental illness constitute only a small portion of the perpetrators of gun violence in this country,” Paul Appelbaum, MD, professor of psychiatry, medicine, and law at Columbia University in New York City. told Medscape.

The analysis covered 82 incidents of mass murder in academic settings including schools, colleges, and universities. The average number of victims of these incidents was eight. All 82 incidents were initiated by men (mean age 28), and 67% were Caucasian. About two thirds (63%) involved guns.

More than three-quarters (77%) of all perpetrators of mass murders in academic settings had no recorded history of psychotic symptoms. (emphasis added by author)

Swiss Cheese

To extrapolate data and draw conclusions from an existing data set, the cohort needs to be at least mildly historically similar. All this analysis suggests is that 77% of the shooters were not yet diagnosed as suffering from a mental illness or had insufficient coping mechanisms to deal with the stresses they faced. The authors conclusions, that only 23% of the shooters suffered from mental illness is an overreach of monumental proportions.

Most modern research suffers from these biased slants, which either lose sight of their controls or interpret data in wildly irresponsible fashion. All the more sad, as the true value of the data is lost behind an overriding narrative the authors wish to justify. What is clear from this analysis data, is that our systems for managing and identifying mental illness and related conditions are flawed. As is the care we offer to those diagnosed.

A significant majority of these shootings may have been prevented had individuals with a myriad of life challenges or psychological struggles been flagged. This begs the argument, why did the 23% slip through the cracks if they had been diagnosed and were, one would assume, under treatment?

These incidents, targeting young children by individuals who are themselves still just teenagers or newly minted adults, are a new phenomenon. Discovering the “why” matters almost as much as restricting access to weapons.

What can the 82 teach us?

Numerical data in this instance, used as it was, for the analysis above, is of little import and can be manipulated to suit any agenda. What researchers should instead be pursuing are the 82 lives that led to these horrific events.

Who were these young people, social backgrounds, family, schooling, infractions with law and authority, medical histories, friendships, potential triggers, medication, anything and everything that can be found that relates to their lives. Examine this and patterns will emerge. Patterns that may very well point the finger of blame to society, broken families, flawed mental health policies and the social stigma of reaching out for help – even in-patient care.

Identifying these patterns and potential triggers matters. Our human capabilities no longer limit us and AI can be incorporated to search social media for matches, allowing for early intervention. Teenagers or young adults do not just pick up a weapon and commit mass murder. They progress, in increments, to this course of action.

There are always signs.

Often we simply fail to see the signs and sadly, when we do pick up on them, we tend to ignore them – we cannot image that they will lead to something so horrible.

But, there is another challenge – access to mental health help. Ask anyone who needs to find a therapist how daunting the task is. It can take months, sometimes more than a year, to secure an appointment with someone with experience to address serious mental health challenges.

Again, this is unsustainable in a society where stable parenting is becoming an archaic concept, whether by design or necessity. Stable homes are in rapid decline.

The real indictment of this analysis are the diagnosed 23%. They represent the ever-increasing cost of our inability to help children who are crying out for guidance, care and a sense of belonging and purpose. How many lives could have been spared? How many lives will still be forfeit? We can, and must, do better.

Reaching for the closest solution

Mental health issues may be the motivating factor to committing mass murder. The preferred tool of choice for these murders is the assault weapon or other firearm. While we can debate the motivation for each individual heinous act, this choice of tool is far simpler to comprehend. Ease of access.

In countries where access to firearms is limited or non-existent, school shootings DO NOT HAPPEN. In America, gun ownership, legal or otherwise has reached pandemic proportions. It is even questionable at this point if tightening ownership laws and policy changes will have any impact whatsoever on teens being able to find and use weapons designed to maim and kill, so prolific is their distribution in American society.

While we struggle to find ways to prevent these tragedies from a mental health perspective, an arduous and difficult task, surely removing the preferred tool from the equation makes far more sense. No access to guns equates to no school shootings. A globally proven fact.

The post Why It is Imperative We Redefine Mental Illness and How We Treat It appeared first on Medika Life.

CAR T is an effective treatment for some hard to treat cancers. This “living drug” is made by extracting killer T cells from the body, manipulating them to target cancer cells, multiplying the newly engineered cells and infusing them back into the body. Development over the last forty years has evolved the precision, efficiency and safety of this technology. Arguably the best example is the treatment of  B cell cancers.

B cells to B cell cancers

CUSABIO Link Added

Figure 1 illustrates the development of antibody cells. B cell maturation begins with stem cells in the bone marrow and is completed with the antibody producing plasma B cells.

Typically, threats to the body leave trails of foreign antigen which can be followed. B cells detect these antigens and proliferate to eliminate pathogens, but these numbers quickly subside. This is done by design. The body regulates this process to ensure the bloodstream is not flooded with too many antibodies to prevent normal function. However, this system can go awry at any point. B cell precursors, intermediate cells or plasma cells can mutate and grow uncontrollably, causing damage to the body rather than shielding from it. When this happens, the immune system weakens and B cell cancers result.

LYMPHOMA CANADA

B cell lymphomas originate from the lymphatic system organs, vessels and tissues, such as the lymph nodes or the spleen. In contrast, leukemias circulate in the bone marrow and blood instead of the lymph organs. Although multiple myeloma is also a cancer of the bone marrow, it entails the abnormal growth of plasma B cells in particular.

Treating B cell cancers

Chemotherapy and radiation most successfully reduce the size and quantity of B cell tumors. Partial remission is very achievable, but complete remission—the total absence of cancer— is much more difficult to attain. For many, the cancer may temporarily recede for months or years after treatment before recurring. And when the cancer recurs, it can be resistant to treatment.

CAR T cell therapy addresses this problem by transforming patient immune cells into an anti-cancer drug. Cells are taken from the body and modified to detect the tumor cells. CAR T cells are fitted with a fusion protein (scFV, Figure 3) made from antigen-recognizing regions of antibodies. This component is typically engineered to target CD19, a B cell antigen known for its role in B cell signaling. This protein is found in B cells of all stages and is present on the surface of many B cell cancers. CD19 is not found on hematopoietic stem cells—those which have yet to mature and gain purpose; as a result, the therapy is less likely to target non-cancerous immune cells, an ideal quality in a therapeutic target.

FIGURE 3: CD19 is an antigen expressed on cancer cells. CAR T cells are fitted with an antigen recognition domain, a single chain variable fragment (scFV), to target the CD19 on the surface of these cancer cells. Once the antigen domain binds to the cancer cell, the CAR T cell can induce apoptosis to eliminate the tumor cell.

BRITTEN, OLIVER, ET AL. 2019 Link Added

Once the CAR T cell binds to CD19 on the tumor cell, several signals are released from the endodomain that trigger cell death of the tumor cell through apoptosis. The co-stimulatory molecules found in the interior of the CAR T cell allow it to multiply and persist in the body.

Normal T cells from the body lack the precision of this antigen recognizing protein and usually require specific proteins—major histocompatibility complexes—to present the antigen and facilitate similar binding. CAR T cells forgo these steps, producing superior hybrid molecules which combine antibody detection with T cell signal transduction. This synthetic engineering defines the chimeric nature of Chimeric Antigen Receptor T cells.

Why CAR T therapy?

As of publication, CAR T is only considered after standard cancer treatments have run their course. Why, then, do people turn to CAR T therapy if it is only considered after several other lines of treatment?

For those who have B cancers which are unresponsive to alternative anti-cancer treatments, CAR T can deliver lasting remission and extend life expectancy by several years—sometimes without additional treatment.

NOVARTIS

For example, one study revealed that 44% of young patients with acute lymphoblastic leukemia (ALL) live at least five years without relapse after CAR T therapy. This is especially remarkable given how difficult it can be to treat the condition and the less than 10% five-year survival rate. Approved CAR T therapies also exist for patients with diffuse large B cell lymphoma (DLCL), follicular lymphoma, mantle cell lymphoma and multiple myeloma.

ACCELERATING CANCER IMMUNOTHERAPY RESEARCH

There is a caveat—it is possible to experience relapse after CAR T therapy. One contributing factor is CD19 antigen escape, a type of CAR T resistance. As illustrated in Figure 5, patients with antigen escape develop cancer cells which no longer express CD19 and thus escape recognition by CAR T cells. So while CD19 targeting has proven effective, this phenomena highlights the need to find alternative antigen targets to improve the drug’s efficiency.

One possible solution is dual targeting CAR T cells. By engineering T cells which detect more than one antigen on cancer cells, the therapy has a greater chance of attacking tumor-only cells and overcoming antigen escape. Current contenders include dual targeting of antigens CD19 and CD22, as well as CD19 and CD20.

Summary 

CAR T shines best in solving what other therapies cannot. When other lines of cancer treatments such as chemotherapy or radiation cause relapse, CAR T therapy often provides a more lasting remission. There’s promise for these engineered T cells to become even more effective in the future with the advent of dual-targeting CAR T cells. And while none of the six FDA approved CAR T therapies are currently used as first-line treatment, developments are underway to establish this innovative technology as a primary line of defense. This is a major step forward for treating B cell cancers, and we can anticipate more to come.

The post The Remarkable Research Of CAR T Therapy: B Cell Cancers appeared first on Medika Life.

Several previous studies have concluded that SSRIs can significantly reduce the risk of depression. However, a recent study refutes this.

A new study from a team of British, Swiss and Italian scientists evaluated the evidence for whether depression is associated with serotonin activity. They questioned the use of antidepressants and the serotonin theory of depression.

So far, the theory we knew is that depression is the result of an imbalance in brain chemicals, especially serotonin. This theory was influential for decades and provided important justification for the use of antidepressants.

The decreased levels of serotonin were first linked to depression in the 1960s. This theory was widely accepted in the 1990s with the advent of Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants, which can temporarily increase the availability of serotonin in the brain.

Serotonin is a chemical courier that carries signals between nerve cells in the brain. It’s thought to have a good influence on mood, emotion and sleep.

NHS said SSRIs are the most commonly prescribed type of antidepressant. They are generally better than other antidepressants because they have fewer side effects. Although people may have the side effects, it is only troublesome at first, but they usually get better by the time. It’s also safe to use during pregnancy.

Fluoxetine is probably the most popular SSRI (sold under the brand name Prozac). Other SSRIs include citalopram (Cipramil), escitalopram (Cipralex), paroxetine (Seroxat), and sertraline (Lustral).

One in six adults in the UK and 13 percent of Americans take antidepressants. Surveys show that 80 percent or more of the general public now believe that depression is caused by an imbalance of brain chemistry.

The latest study, published in Molecular Psychiatry on July 20, 2022, analyzed 17 previous studies starting from 2010 on serotonin levels in people with depression.

In the study, Professor Moncrieff and colleagues aimed to capture all the relevant studies that have been published in the most important research areas on serotonin and depression. The studies included in this review involved tens of thousands of participants.

As a result, there was no evidence that depressed people had lower serotonin levels or abnormal serotonin activity compared to non-depressed people.

“It’s always hard to prove anything negative, but I think we can say that from the many studies done over the decades, there is no convincing evidence that depression is caused by a serotonin disorder, particularly by lower levels or decreased serotonin activity,” says Dr. lead author of the study, Joanna Moncrieff, a professor of psychiatry at University College London and a consultant psychiatrist at the North East London NHS Foundation Trust (NELFT).

The study doesn’t necessarily label SSRI use as ineffective but suggests that SSRIs don’t treat depression by improving serotonin levels. They found no difference in serotonin levels between people diagnosed with depression and healthy people, although polls show that 95 percent of the public believes this. Lowering serotonin levels in healthy volunteers also did not lead them to develop depression.

Is SSRI Still Effective?

However, many experts in this field have different opinions. They agreed that depression is a heterogeneous disorder with potentially multiple underlying causes. It’s not like a simple disease with just one direct cause.

Allan Young, director of the centre for affective disorders at the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, said that depression is not only because of imbalance theory, it’s related to biopsychosocial model.

“Many of us know that taking paracetamol can help with headaches and I don’t think anyone would believe that headaches are caused by not having enough paracetamol in the brain, the same logic applies to depression and drugs used to treat depression” — Michael Bloomfield

Michael Bloomfield, a psychiatrist at University College London said there is consistent evidence that antidepressant medicines can be helpful in the treatment of depression and can be life-saving.

Many other experts agreed that antidepressant medicines are one type of treatment alongside other types of treatment like psychotherapy (talking therapy). Taking SSRIs can still help treat depression, although it may not get to the root of the problem.

The effectiveness of antidepressant medication is different for each individual. That’s why it’s important that patient care is based on each individual’s needs and reviewed regularly.

Every medicine, including SSRIs which have been used for patients is based clinical trial evidence. This review does not change that.

We would not recommend for anyone to stop taking their antidepressants based on this review, and encourage anyone with concerns about their medication to contact their GP.

The post Depression isn’t Caused by Low Serotonin Level, Are SSRIs still Effective? appeared first on Medika Life.

From evolution to the industrial revolution, this is a recurrent theme for humanity and all life on earth. We receive a kick in the ass and move (sometimes crying and screaming) into the future. Sometimes, it’s a singular event that drives a profound transformation—remember those dinosaurs and that asteroid?  And if you use your imagination, you might even see that horrific sphere in the sky and conger some images of the COVID-19 virus. Sometimes it’s a cluster catastrophic events or a confluence of magical things. 

Change is disruptive.  But adoption is gradual.  And that where people get confused.

The year 2021 was certainly disruptive.  And it was defined by COVID-19 and void of innovation that perfectly reflected the difference between disruption and adoption. Certainly, there were important breakthroughs including therapeutics and vaccinations.  But failure was also a defining aspect of a tumultuous year. Adoption can drag its feet…

Clinical uncertainty was met with the demands of rapid action and resulted in the complexities of innovation, confusion, and adoption. COVID-19 compressed years of science, pharmaceutical development, technological advances and clinical practice into just months—sometimes even days. And then, layered moral imperative of action into this equation. The lessons learned from 2021 are vast. But, in many instances, these lessons were driven by events, or, if I may, singularities that helped shape and drive action.

It seemed that almost every day in the past year provided new data, insights, and guidelines that helped informed clinical practice. Yet, this pushed clinicians away from the “clinical comfort zone” into more a “risk/reward” posture where conformation was either antidotal, pre-published, or driven by societal and political pressures. Consensus—from patient to clinician—was sometimes difficult to find. But bravery, from thought to deed, was frequently at hand.

Today, we are around the corner from another asteroid or spike protein.  But we are also at the center of another confluence that offers the potential to transform and protect humanity from those fireballs in the sky.

Social need, technology, genomics, artificial intelligence and a host of factors are aligned for more than a change, but a tectonic shift of unimaginable proportions. These are coming at us with the jolt of disruptive transformative that can make us cling to a safer and more predictable past. But that’s the nature of transformation.  It’s sudden and shocking.  But the human side of that journey may not always align. 

The traditional vision of our future and of transformation is our desire for  “the same but better.”  From the emergence of the electric car (a transition) to the introduction of a new beta-lactam antibiotic with better tolerability and spectrum of coverage (another transition), we adopt in baby steps.  But technology can often loom larger and step more broadly. 

That’s where we are today.  Look up and you’ll see it.  We are just heartbeats from our next inflection point. The question isn’t only about the wonder of technology to help solve these conflicts, but the bravery of humanity to move forward.

The post Perhaps, A Braver New World appeared first on Medika Life.

This research paper is a very confusing read, even for someone who is quite familiar with this kind of research. Yet what is said in the paper is crucial to the case being made by Jean Twenge (and Jon Haidt) that government intervention is urgently needed to curb the harms of social media to the mental health of teens. I’ll use the abstract of the paper to discuss how to find flaws in a research study that is intended to influence public health policy.

Parents and school teachers and administrators cannot be expected to interpret original research studies on their own. But they might learn from discussions like this one to be more skeptical of experts who claim their advice is based on social science, but who make emotional appeals and rely on anecdotes to rouse their readership into action.

The ratio of emotional story-telling to actual scientific evidence is very high in stories in the popular press expressing alarm about the damaging effects of teen girls’ use of social media on their mental health.

There is an excess of hype and drama about this topic, even in op-eds in the New York Times. When in doubt, be skeptical of social scientists who try too hard to convince you that they are correct and that other experts have just not noticed something that is obvious to them.

In a widely discussed article, Jean Twenge says that she has been studying generational trends in mental health for over 25 years and that she never before found such a dramatic change in mental health as she saw around 2012.

Have Smartphones Destroyed a Generation? More comfortable online than out partying, post-Millennials are safer, physically, than adolescents have ever been.

Around 2012, I noticed abrupt shifts in teen behaviors and emotional states. The gentle slopes of the line graphs became steep mountains and sheer cliffs, and many of the distinctive characteristics of the Millennial generation began to disappear. In all my analyses of generational data — some reaching back to the 1930s — I had never seen anything like it.

Twenge has advice for parents and teachers:

If you were going to give advice for a happy adolescence based on this survey, it would be straightforward: Put down the phone, turn off the laptop, and do something — anything — that does not involve a screen.

Twenge commands special authority because her views are said to be derived from the best available evidence.

However, most of the key research that Twenge and her fellow advocate Jonathan Haidt cite was not conducted by either of them. I suspect that many of the authors of these studies they cite would disagree with Twenge and Haidt’s interpretation of their work, some vigorously so. That situation makes one centerpiece study led that was led by Twenge particularly important.

The key research article by Twenge and her colleagues is here.

Increases in Depressive Symptoms, Suicide-Related Outcomes, and Suicide Rates Among U.S…In two nationally representative surveys of U.S. adolescents in grades 8 through 12 ( N = 506,820) and national..

The article is unfortunately paywalled, but here is its abstract. We can do a lot with it.

In two nationally representative surveys of U.S. adolescents in grades 8 through 12 (N = 506,820) and national statistics on suicide deaths for those ages 13 to 18, adolescents’ depressive symptoms, suicide-related outcomes, and suicide rates increased between 2010 and 2015, especially among females. Adolescents who spent more time on new media (including social media and electronic devices such as smartphones) were more likely to report mental health issues, and adolescents who spent more time on nonscreen activities (in-person social interaction, sports/exercise, homework, print media, and attending religious services) were less likely. Since 2010, iGen adolescents have spent more time on new media screen activities and less time on nonscreen activities, which may account for the increases in depression and suicide. In contrast, cyclical economic factors such as unemployment and the Dow Jones Index were not linked to depressive symptoms or suicide rates when matched by year.

The editors at a top psychology journal, Clinical Psychological Science, and the reviewers the editors picked were obviously impressed enough to recommend the article and its abstract be published in the form that we now see.

I noticed lots of things that made me suspicious because I have higher standards for talking about risks to health than most psychologists do.

• I received excellent training in my Ph.D. studies as a research-oriented clinical psychologist. I received my doctorate in 1975 but then began working in situations where medical scientists and public health officials demanded stricter standards than what was required of psychologists trying to get published in a respectable psychology journal. Lives depended on what a different kind of expert decided about risks from the often limited and flawed data that was available to them.

The COVID pandemic and the quick decisions that had to be made about what advice could be given concerning vaccination, social distancing and lockdowns put this kind of expertise on display. The world-class experts giving briefings on the best of cable news were good at policing each other to avoid exaggerating what was known and to admit they did not know. “We don’t know yet” was often the best answer, as frustrating as it was.

For a start, I expect more information from an abstract than this one provided. The authors did not follow standard advice on what to include in an abstract. I’ll have a future story documenting how abstracts attached to paywalled articles like the one we are discussing here can actually kill people, aside from spreading misconceptions.

Rather than doing their own research to collect new data, these authors relied on existing survey data sets collected for other purposes. This leaves lots of questions about they did this that the authors do not address in a transparent way.

How did the authors integrate this data from different sources in one study? Relying on someone else’s data is attractive and may at first seem expedient, but effectively and validly doing requires a lot of difficult decision-making.

Inevitably, the original researchers did not ask the right survey questions for new research. What questions in the surveys best fit the new issues researchers wanted to address? How could the new researchers verify that their selection from already collected data was most valid and relevant to their issues?

Twenge and her co-authors imply in the abstract that they had been able somehow to integrate the survey questions with information from the national statistics on deaths by suicide. I knew that was bunk. Ethics committees overseeing the protection of human subjects insist the data be anonymized so that identification and matching of people across data sets becomes virtually impossible.

Then, there is the problem of the small number of suicides in this relatively low-risk group. Let’s stop here and apply some numbers I revealed last time.

Any potential risk factors the authors can find in these pre-existing survey questions must pass the test of predicting relatively infrequent events with some percision. The abstract suggests the authors may have succeeded (“which may account for the increases in depression and suicide), but that would be statistically improbable, given the basic rate of death by suicide and any conceivable fluctuation in the study period of this article.

For 2017, we have about 420 suicides to explain among 20.5 million girls. I wish the authors luck in using whatever fancy statistics they can muster to predict which girls will die by suicide with the risk factors they can pull from other people’s data. Chances are no one died by suicide or only a chance handful from participants in the survey data they acquired. Neither Twenge and her co-authors or readers can tell.

Not being able to identify which of the teens completing the survey died by suicide means the authors will be left making speculative statements beyond what their data allow.

The authors used the term “iGen adolescents” in the abstract to describe the teens they studied. That fits with Jean Twente’s best-selling books, but I was skeptical about such a sweeping term being able to capture much of the similarities and differences in an increasingly diverse and divided America in the association of use of social media and mental health.

Was any similarity of teens falling in this age range more important than the vast range of differences? Consider one white teen having alcoholics or Trump supporters for parents versus another teen having teetotaler Hindu parents who insisted that their teen study hard enough to go to medical school and become a physician? White teens with two Ivy League faculty as parents versus a Black teen raised by a single grandmother who dropped out of high school and does not have internet? Versus a Black teen raised by a single grandmother who dropped out of high school, but the great of the story is the teen’s mother was an innocent victim of random gun violence and the grandmother insists the teen fulfill the mother’s dream and go to college, no excuses accepted?

I could generate thousands of these kinds of contrasts, and some would be quite absurd.

The final conclusion where I seem to be headed is that a generational label like iGen or Generation Z cannot capture much of variations among teens — or across an individual teen’s transition into adulthood and afterward.

“iGen” [Don’t you like the cool choice of labels so that you automatically think of having “iPhones” as what 25 million American teen girls have in common?] might serve to highlight some things teens that might be missed that teens have in common. Surely it misses a lot of things teens don’t have in common, whether they are from radically different backgrounds or with nearly identical demographics but just different in the place of social media in their lives.

The authors end their abstract with straight-faced reassurance that they controlled for “cyclical economic factors such as unemployment and the Dow Jones Index,” matched by year. I can just imagine some badass experts at conferences I have attended who would lie in wait for a speaker to say such a silly thing.

Academics who think their research saves lives can be real a*holes when dealing with other academics whose research they think will never save any lives.

Imagine the response of experts accustomed to identifying health risks from correlations found in survey or surveillance data. Unprepared for what they would hear, some would have spilled coffee on their fancy suits and chocked on the stale Danish from the free conference breakfast as they scrambled to correct the speaker, not allowing anyone to discuss what else the presenter had to say.

I can imagine the string of cliched criticism that could be unleashed.

“Of course, you know that correlation does not equal causality.”

“You can’t do magic with statical controls of correlations when all you have is somebody else’s survey data they collected for some other purposes.”

“What a dumb choice! Are you a psychologist who does not understand regression analysis or do you have books to sell at the conference? Will your next slide tell us where to find your Tedtalk?

Maybe the badass expert would be in an uncharacteristically charitable mood and simply explain:

“I appreciate your effort to find support for a hypothesis that excites you.You should realize that you are relying on statistical controls to settle some issues of causality that are not readily solved. If you were to rely on such controls, you are first making the assumption that you have isolated all the variables that could possibly explain away your findings. I don’t think these crude economic indicators begin to do that. Secondly, you are assuming that these variables are measured without error. I don’t think an economist would say these two variables perfectly measure year to year differences in the economy affecting either teen’s use of social media or dying by suicide.”

One final cynical a*hole comment before we move on —

“If we had used your approach to statistical analysis, we would have concluded at the early days of mystery in the HIV/AIDS epidemic that someone using poppers to enhance orgasm during casual sex or simply having too many Judy Garland LPs in their vinyl collection was a modifiable risk factor.”

Frightened and humiliated, the psychologist trying to finish their talk would miss a very serious and useful message that was being disguised here.

Not knowing what you are doing with bad data and a computer program can lead to all kinds of compelling, but spurious correlations to get worked up about, some more plausible for a while than the modifiable risk factor you are listening for in very noisy data.

So, just what did Twenge and colleagues do with “two nationally representative surveys of U.S. adolescents in grades 8 through 12 (N = 506,820) and national statistics on suicide deaths for those ages 13 to 18, adolescents’ depressive symptoms, suicide-related outcomes, and suicide rates increased between 2010 and 2015?”

That is a true mystery that is never clarified in this abstract. I was stumped at first. I gave the authors the benefit of a doubt and thought maybe they did some kind of prospective analysis, looking ahead and predicting later things that happened to individuals from their earlier responses on surveys.

I had to get a copy of the paywalled article. The overall design of the study was still difficult to decipher from the methods section, where it should have been laid out in detail and given a name, like case-control or cohort study.

I eventually figured out that the authors did not have two “nationally representative surveys of U.S. adolescents.” They had over two dozen cross-sectional retrospective studies (a one-time survey asking about the past year) with nonoverlapping samples and important differences in the questions that were asked. No questions at all about social media in the survey for some years (!).

This dog’s breakfast of a design for this study will be the topic of my next article about this study, as we dig deeper into what can reasonably be claimed from this study and what cannot — if we stick to principles of best science, not just good story-telling.

The post A Stunningly Bad Study Claims Social Media Devastates Teen Girls’ Mental Health appeared first on Medika Life.

I chose to discuss Why We Get Sick, a lecture Maté delivered in London because it puts Maté’s ideas on full display.

The complete video of the lecture was uploaded in August 2019 by How To Academy Mindset. The video is part of a series that includes Jordan Peterson and Bessel van der Kolk. On Google, the YouTube video is re-titled Dr. Gabor Maté on The Connection Between Stress and Disease.

Struggling to get through this video, my mind wandered to thoughts of how lucky I would have been to be in London, maybe at the same theatre, when a true Canadian gift to the world, Leonard Cohen performed the concert captured in the Live in London 2-CD set.

Like Maté, Cohen is a member of the Order of Canada, the highest honor the Crown gives to a civilian. Both must somehow exemplify the order’s Latin motto, desiderantes meliorem patriam, meaning “they desire a better country.

”Live in London (Leonard Cohen album) – WikipediaLive in London is a (double) live album

After a few minutes, I could not stand watching Gabor Maté piling bonkers claims on bonkers claims anymore. It was just too painful to endure the stream of nonsense he was spouting, but I felt it was my duty.

I had taken the challenge of exploring and explaining the hidden-trauma/polyvagal theory/psychedelic psychotherapy nexus of nonsense. . I needed to provide a report of an investigation in progress.

Taking a break, I sought relief in listening to The Future, my favorite song in Cohen’s 2-CD set.

My wife is grateful that I have noise-suppressing headphones that keep my noise out of her ears. She finds Leonard Cohen’s music depressing. She is not a music snob, having played a variety of instruments in rock and country-western bands. She is just more susceptible to the mood contagion from music and language than I am.

I can’t explain to her why I find Cohen’s apocalyptic, dystopic vision in The Future an antidote for Maté, who has a similar vision. I guess Cohen is entertaining and does not tempt me to argue with his “Truth” delivered in well-crafted songs with brilliant lyrics.

Maté offends me by preaching a “Truth” with a call to action.

Maté urges us to abandon what has evolved over time to be evidence-based solutions to health and social problems. We should get involved in long-term, perhaps interminable therapy to exorcise the demons of trauma hidden in our subconscious.

There is no evidence that this prescription would improve our health or extend our life, but Maté claims we would be living more authentically.

The large, well-dressed crowd packing the London theatre enthusiastically cheered as if Gabor Maté were a rock star when the emcee announced:

I am honored and thrilled to introduce you tonight to the renowned physician Dr. Gabor Maté, one of the world’s leading experts in trauma, child development, addiction, and the relationship between stress and disease, please give him a huge welcome.

I am not embarrassed to admit I did not know that Dr. Maté was an expert of such eminence. I looked up his name in the usual places where such eminence should be documented, like Google Scholar. I could find insufficient evidence that he deserves such accolades.

A lot of people are convinced otherwise. They listen intently and find validation in the wild things that he says. I thought it was worthwhile to probe a bit of stuff he said in this lecture.

Maté comes to the podium, looking distinguished, but a bit haggard and world-weary. At first, his eyes are nearly closed. He squints and discloses that he has 55 minutes to lecture. He announces the topic:

We’re looking at two questions, basically one is what is disease, number one, and number two, how do we understand the human beings’ relationship to illness, which really comes through the heart of what is humanity really now.

Whoa, drag me into shallow waters before I go too deep. I do not think you will lend me enough of your attention to answer these questions, nor do I feel up to it.

I admit I was tempted to pounce on this next statement:

Western medicine in which I was trained sees illness or the whole person is somehow a random victim of either genetics or external invaders such as bacteria or virus or toxins or possibly as even a culpable instigator of their own pathology by certain so-called lifestyle choices like eating too much drinking too much or smoking

I developed acute genre confusion. I could not decide whether Maté was making a falsifiable scientific claim, trying to practice philosophy with only a degree in medicine, or reciting bad poetry.

I regained my confidence in my ability to discuss Maté when he said soon thereafter:

Let me just give you three medical facts here and you’ll see immediately how inadequate and insufficient the Western medical perspective is in explaining these facts…

The first fact there is a study that was done in the United States last year that shows that the more episodes of racism an American black woman experiences, the greater the risk for asthma.

Let me give another fact. In the 1930s and 40s the gender ratio of multiple sclerosis — which is an inflammatory degenerative disease of the nervous system — was 1:1. In other words for every man, there was a woman diagnosed. You know what the ratio now is? it’s three and a half women to every man. That immediately tells us it can’t be genetic because the genes don’t change in a population over seven decades or even ten decades or longer.

Number two, it can’t be diet because that doesn’t change for a population. It didn’t change more for women than for men. Nor can it be the climate. There is something going on and whatever it is it can’t just be biological now.

What’s interesting is that when you look at how you treat asthma. If you give to open up the airways and to suppress inflammation that happens in the asthmatic airway you give inhalers or medications by mouth, which are copies of adrenalin and cortisol.

Adrenaline and cortisol are stress hormones of the body. I’ll talk about them later. They’re secreted by the adrenal gland in response to a threat so there’s a drone and cortisol. So, we’re treating asthma with stress hormones. How do we treat multiple sclerosis?

Where this is headed is Maté will explain that everything we don’t understand about health and disease, everything that is inadequate in Western medicine is a matter of ignoring the role of stress and hidden trauma in causing illness and death. Shortly into the lecture, we will un into an impenetrable fog of pseudoscience and nonsequiturs. I will get off the train before the inevitable wreck ahead.

I found the article to which Maté was referring to his comment about asthma in black women.

Coogan PF, Yu J, O’Connor GT, Brown TA, Cozier YC, Palmer JR, Rosenberg L. Experiences of racism and the incidence of adult-onset asthma in the Black Women’s Health Study. Chest. 2014 Mar 1;145(3):480–5.

Experiences of Racism and the Incidence of Adult-Onset Asthma in the Black Women’s Health StudyChronic stress resulting from experiences of racism may increase the incidence of adult-onset asthma through effects on…www.sciencedirect.com

The authors hypothesized

Chronic stress resulting from experiences of racism may increase the incidence of adult-onset asthma through effects on the immune system and the airways.

We conducted prospective analyses of the relation of experiences of racism with asthma incidence in the Black Women’s Health Study, a prospective cohort of black women in the United States followed since 1995 with mailed biennial questionnaires.

The authors used a large data set that had been collected without their specific hypothesis in mind. They had to improvise in reducing and analyzing the data.

An everyday racism score was created based on five questions asked in 1997 and 2009 about the frequency in daily life of experiences of racism (eg, poor service in stores), and a lifetime racism score was based on questions about racism on the job, in housing, and by police. We used Cox regression models to derive multivariable incidence rate ratios (IRRs) and 95% CIs for categories of each racism score in relation to incident asthma.

*The IRRs were 1.45 (95% CI, 1.19–1.78) for the highest compared with the lowest quartile of the 1997 everyday racism score (P for trend <.0001) and 1.44 (95% CI, 1.18–1.75) for the highest compared with the lowest category of 1997 lifetime racism. Among women who reported the same levels of racism in 1997 and 2009, the IRRs for the highest categories of everyday and lifetime racism were 2.12 (95% CI, 1.55–2.91) and 1.66 (95% CI, 1.20–2.30), respectively.\

*Given the high prevalence of experiences of racism and asthma in black women in the United States, a positive association between racism and asthma is of public health importance.

There is no surprise in these results. I do not think that anyone having the expertise to interpret these results would find cause to lose their faith in Western medicine.

The authors discarded the middle half of their sample, based on subjects’ scores on everyday racism. That is not a terrible decision, but the strategy inevitably exaggerates the size of the effect that will be reported. I prefer analyses that do not involve throwing away half the data.

If we are looking for determining effect sizes of noteworthy public health significance, I think a reasonable rule of thumb is IRR = 2.5. If we are going to ramp up and demand intervention, the consensus is IRR = 4.0. We can quibble about these somewhat arbitrary cutoffs, but I think experts would still agree that the effect size found in this study is not impressive.

These are correlational data, so we have to be careful about making causal interpretations. We have to acknowledge that we have a crappy self-report measure constructed after the authors obtained this data set. We have to contend with an incomplete specification of variables that need to be statistically controlled and crude measurement. These are standard critiques of such studies.

I would say at least as it is measured in this study “everyday racism” is not causal, but a risk marker related to other risk factors that might be suitable for intervention. I would say that modifiable risk factors were exposure to dust mites, asbestos, cigarette smoke, and poor air quality in cramped, inadequately ventilated living spaces. I would add poor access to quality medical care, specifically inadequately managed respiratory infections and lack of insurance.

I have some experience with this population. I collaborated with Dr. Jen Culane on the Philadelphia Preterm Birth Prevention Project and wasthe Principal Investigator in my own NIMH study of socially disadvantaged inner-city postpartum women in Philadelphia, mostly black.

As the authors of this study, I am convinced without ever seeing their results, that both racism and high rates of incidence (onset) of asthma are serious problems. Subtle and blatant racist acts against black women are highly prevalent and objective, not subjective. We do not have to go rooting in the subconscious of black women to find evidence of this racism.

However, I am not convinced that these particular findings add to what we already know.

Figuring out what to do about increasing rates of new cases of asthma among black women involves problem-solving that applies evidence accumulated using the diagnostic categories supplied by medicine.

The diagnostic categories have undergone considerable evolution over time, revision of what signs and symptoms, what lab test values to include or exclude, based on how they worked in predicting associations among variables and improving health outcomes. Biomedical research is involved but includes microbiology, immunology, and also epidemiology, including social determinants of health. The goal is to bridge these fields, to establish connections that make a difference in health outcomes.

To call this “Western Medicine’ is an act of cultural imperialism. If the rest of the world had survived to now without the influence of the West or Capitalism or whatever, it would be because similar methods had evolved and had produced similar knowledge.

Casually attaching such labels to phenomena his audiences do not understand scores points with them. It allows Maté to dismiss the knowledge and tools we need to prevent new cases of asthma among these women and reduce the toll of asthma among those women who have already developed this chronic, recurring condition.

Maté paints a cartoonish caricature of medicine locked in silos. He confuses the maps that specialist researchers and clinicians use with the territory they cover. There is so much complexity in methods and findings in immunology. While those who study immune function should be able to communicate with those who are experts on the sources of environmental exposures like mites or black mold, but they cannot reasonably be expected to be experts in those areas.

Overspecialization in research and clinical practice is an important issue, especially for the management of difficult-to-diagnosis, multiple comorbidities with multiple medications. Management must collaborative care between professionals and especially with active patient involvement.

There is no cause for lighting anyone’s hair on fire and putting it out with hammers or other cynical, nihilistic high drama of the kind that Maté acts out in front of audiences who come for the spectacle.

I have less to say about Mate’s claims about the changing gender ratio in multiple sclerosis. For a start, studies in different populations do not consistently support a dramatic trend.

Here is one relevant Canadian study in a top-quality journal.

Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, Ebers GC, Canadian Collaborative Study Group. Sex ratio of multiple sclerosis in Canada: a longitudinal study. The Lancet Neurology. 2006 Nov 1;5(11):932–6.

Sex ratio of multiple sclerosis in Canada: a longitudinal studyIncidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a…www.sciencedirect.com

The article summarized the existing literature

Incidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a longitudinal population-based dataset of patients with multiple sclerosis obtained over more than three decades, we did not show a difference in time to diagnosis by sex. We reasoned that if a sex-specific change in incidence was occurring, the female to male sex ratio would serve as a surrogate of incidence change.

The study found:

The female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3·2:1 in Canada. Year of birth was a significant predictor for sex ratio (p<0·0001, χ2=124·4; rank correlation r=0·84).

The authors’ interpretation:

The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women. This rapid change must have environmental origins even if it is associated with a gene–environment interaction, and implies that a large proportion of multiple sclerosis cases may be preventable in situ. Although the reasons why incidence of the disease is increasing are unknown, there are major implications for health-care provision because lifetime costs of multiple sclerosis exceed £1 million per case in the UK.

This is solid, normal science, representing one step on the path to finding a solution, not at all revolutionary or cause for the fuss that Maté is making.

I’ll pass on commenting on Maté’s claims that we treat asthma or multiple sclerosis with stress hormones. Similarly, for his leap that these “facts” justify a deep dive into the subterranean world of subconscious hidden trauma accumulated in early life.

I have collaborated in the successful writing of major grant applications for these diseases. I am sure the grateful principal investigators would answer any questions I forwarded them, but I think they would think I was smoking medical cannabis if I asked them to comment on choice direct quotes from Maté’s talk.

Leonard Cohen engaged in banter with his audience expressing thanks for the ‘geographical and economic inconvenience’ they had suffered to come to hear his concert in London. Of course, he did not have time set aside for questions and answers at the end. Maybe he did an encore.

Members of Maté’s audience competed at the end of his lecture to get his opinion on a variety of health and social issues.

I guess they thought they had enjoyed a scientific lecture from a rock star celebrity, not a rock concert. I cannot fathom why and I will have to do some more investigation but I will have to prepare if this means I have to watch any more Maté lectures.

Perhaps I can find a lecture that is mercifully short. I will keep some Leonard Cohen music handy, like an epi-pen that I can use if I find myself experiencing an adverse reaction.

Postscript

I was expecting to upload this article last night, but an intense storm rushed through my village, uprooting trees, and cutting off power and internet. I refuse to think that was some divine sign that I should post it.

Sitting in the dark, I reflected on these presumably intelligent English people sitting through Maté’s lecture without leaving, and then some of them asking questions with no challenge to the outrageous things he had said.

The next time they went to a GP or medical specialist, would they chastise her if she did not start by asking them about their hidden trauma? If their parents had cancer, would they rush them into trauma-informed treatment or would they seek the best oncologist available and maybe even get a second opinion.

I think not. The audience knew they had not been to a Leonard Cohen concert or a lecture that should change their patterns of health care.

The audience knew they had been to church and had heard an eminent preacher from Canada, Gabor Maté’s who did his best to whip up an old-time sermon with terrifying hellfire and damnation. Some of the audience talked about his religion with him but they knew they did not have to do anything different in their lives. They were familiar with this genre. They would continue to seek the best health care available, even outside the National Health Service if they had to.

You don’t go to sermons like this and then go home and do anything differently. No intelligent person does that.

My worry is that many people who are respectful of the authority reflected in membership in the Order of Canada, might take Gabor Maté’s words literally and seriously.

I worry about my Canadian neighbors who are not so savvy or cynical. I worry about Americans who are already heeding what Prince Charles and Prince Harry say. Their lives are put at risk by the serious nonsense that Gabor Maté is spreading about cancer and other illnesses and his contempt for medicine and science more generally.

The post Gabor Maté’s Bizarre Ideas on Connections Between Stress and Disease appeared first on Medika Life.

Many people do not inspect what is reported before forming an opinion or accepting someone else’s opinion. The actual results are certainly worth a look.

But I think we need to consider whether the authors even were asking the right clinical question.

By narrowly construing the trial as a test of the efficacy of MDMA for PTSD, the authors may have missed some limitations. The trial is NOT primarily being a drug trial, but more properly, a trial of a drug always being delivered in conjunction with a poorly specified and unproven psychotherapy.

I have some relevant background and expertise for forming an opinion about this.

I was involved in various stages of writing and reviewing grant proposals, applications for use of human subjects, and justifications for the burden that studies place on medical patients. I was a co-principal investigator on a center grant with the responsibility of developing and implementing psychosocial interventions combined with drugs. I served on the committee monitoring the progress of a major clinical multisite trial of treatment of depression to prevent heart attacks for safety and data quality. I was an external scientific advisor conducting process evaluations that might reveal what happened in trials for anomalous results.

I have never encountered anything at all like the psychotherapy manual for the Nature Medicine trial of MDMA for PTSD.

If you like, you can wade through the actual manual here, but it is very vague and demands of your time to get to crucial details. Or you can see how promoters describe the treatment in promotional material on their websites, including graphic videos.

I am a clinical health psychologist concerned with delivering the best treatment within the limits of scarce funding. That makes me a mental health services researcher. I am deeply concerned with the lack of assurance that the same psychotherapy was delivered across settings in the trial reported in Nature Medicine.

I could imagine making a bit of a fuss if I were on a committee to evaluate ahead of time whether a major clinical trial of MDMA, a drug that was illegal and otherwise unpatentable could depend on the validity of this treatment and whether it was faithfully delivered.

Basically, investors are asking for a monopoly because they will ensure the safety and efficacy of MDMA by embedding it in a package with their psychotherapy. They claim to be so convinced by a lack of evidence that MDMA is safe or effective outside of such a package. So much so that they will not bother to gather new evidence against the null hypothesis of MDMA being unsafe and ineffective for PTSD.

In the loose, informal atmosphere that occasionally develops in closed meetings, I could imagine my younger self reading juicy sections from the manual, and insisting on playing promotional videos to the committee from the 15 sites that were available to prospective participants during recruitment.

With some degree of mock seriousness, I might have asked whether different music might have elicited a different response from patients, whether the flowers and fake artifacts were necessary.

What if a patient did not welcome what was intended to be the soothing touch of a same or different gender person while under the influence of a disorienting drug and while possibly being stimulated to sexual arousal?

I could expect blowback and protests if I raised the last point. I would come prepared with documentation that sex with a patient had occurred in at least one MAPS trial and that the unlicensed counselor had pleaded, of course, that the sex was consensual.

This claim is outrageous without substantiation. I invite you to find it here. Psychedelic therapy has a sexual abuse problem

I doubt anyone involved in reviewing the data from the trial for the US Food and Drug Administration has ever seen such psychotherapy being proposed to accompany all marketing of a drug. I would love to hear the discussion the review will generate.

Claims that findings are groundbreaking, breakthrough, or otherwise extraordinary deserve more scrutiny and maybe even skeptics thinking longer and harder about what was going on in a study.

Many on social media assume that claims that have made it into a world-class medical journal no longer need to be vetted. They believe that they can take what is said about the psychotherapy in an article in an impressive journal with their critical tools to appraise the study being left in their toolbox.

I am not one of those people. I am hoping to convince some readers that they do not want to be that kind of person either. That is generally my goal in teaching and writing about clinical trials, but I think that the Nature Medicine article is a particularly good teachable moment. The authors and their backers are screaming so loudly and incessantly that there has never before been such a study.

I am getting some pushback to my skepticism about the trial, only some of which will be disclosed here. There has been an effort to stop the publication of my critiques and remove what I have published so far. If what I have written were patently stupid, I think that would be discovered soon or later and what I have published could be left published to embarrass me.

The threshold should be high for making an article disappear, rather than simply flagging with a statement of concern or retracting it.

I first probed a fawning New York Times article about the trial with improbable claims, obviously written with the collaboration of the Nature Medicine authors. I complained that the journalist should have protected readers by getting her own experts and by providing an independent critical appraisal.

Is the New York Times a Shill for Promoters of Psychedelics?
Evidence that the newspaper is not sufficiently detached from promoters to provide an open-minded but skeptical…medium.com

Next, I limited myself to a single sentence in the abstract of the Nature Medicine article. I wondered aloud why so few “experts” were speaking out about a reporting of this study that was so wrong in so many ways.

The MDMA-Assisted Therapy for PTSD Study: What You’ll Get Wrong
Seldom have so many experts had such strong opinions about an open-access drug trial they did not read carefully…medium.com

In the last installment, I focused on only the list of authors, the contributions that justified their getting authorship, and the authors’ affiliations. I concluded that there was good reason to treat the study not as strictly as a pharmacological trial but as a trial of psychotherapy in combination with either a drug or an inert pill-placebo. I proposed:

This reframing involves a very different set of criteria that could expose a different set of inadequacies in the trial of MDMA as a treatment for PTSD — such as the lack of standardization of the therapy across settings and therapists.

Surprises in the Authorship of a Paper About MDMA to Treat PTSD
Some of the 39 authors practice alternative medicine and unvalidated psychotherapies, with little research experience

I am pleased that my intuitions have generally been confirmed that there is something wrong going on with the way the study is being sold. Yet, I wince at some of the things I have written and mistakes that may have been made. Even if I have been wrong in some respects, I could be on to something. We could reach a consensus that the study is flawed, at least enough to temper the authors’ claim made in the abstract and echoed all over the world:

“We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.”

The authors and their sponsors are pushing for expedited review and approval by the US Food and Drug Administration. This was hastily done with intravenous infusion of ketamine, which — as I covered here — did not go so well.

One reader,Julian Willet, MD is unconvinced enough by what I have been writing to post a comment:

Nature Medicine is a well-respected journal and generally decently trusted (though naturally, some papers can get through the cracks). Perhaps that occurred, but I cannot say. I skimmed the paper and the results are significant/impactful, which would make it an attractive paper to publish even if there could be potential controversy.

I asked the opinion of an expert statistician who has consulted on trials of psychedelics and he replied:

*I have read the results section a few times since published (and compared) to protocol. I would say that generally it looks sound and I would guess they have a professional statistician in the team or use a consultant. That’s from what I can deduce from the paper.

His comment left me self-doubting and defensive. I went back to the Acknowledgment section of the article. I counted the number of therapists listed. I replied to him, “What if there are 40 therapists?”

Suffice to say, that reply changed his mind and got him doubting too.

Only as I sat down to write this article, did I realize the implications of what I had written to him.

The Nature Medicine article portrayed the clinical trial as evaluating whether MDMA was superior to an inert pill-placebo under tightly controlled conditions. It would be reassuring to know if the results did not vary across the clinics and providers, but we probably should not expect any surprises.

It is simple enough to standardize the providing of a pill and not expect much variation across sites and providers. Not so with psychotherapy that is so incompletely specified. I expect lots of variation in how the psychotherapy is implemented with which patient, with which therapist, in which setting.

The trial is initially blinded so that neither the clinician nor the patient knows whether the patient is assigned to get the MDMA or an inert substance in an identical capsule. The trial quickly becomes unblinded in the first half-hour of the first eight-hour session. There are three such sessions. I would be especially concerned with the improvisation that would occur once the patient and therapist knew whether the patient was getting the MDMA.

I do not have to prove my skepticism is correct. The burden is on the authors of the Nature Medicine article to prove me wrong. They are facing an evaluation by the FDA with a lot at stake.

Stay tuned and we will probe the Results section, aided by the lens I have developed in this article.

The post Before Looking at the Results of the Paper on MDMA to Treat PTSD… appeared first on Medika Life.

This author has built a reputation on his disdain for evidence-based psychotherapies. His books and workshops promote questionable psychotherapies with dubious mechanisms of mind-body interactions, backed up by dramatic anecdotes, not evidence.

Who could that be?

This revelation only encourages me to examine the trial more closely as an evaluation of psychotherapy combined with medication — not as primarily as a drug trial, as most everyone else has been doing.

This reframing involves a very different set of criteria that could expose a different set of inadequacies in the trial of MDMA as a treatment for PTSD — such as the lack of standardization of the therapy across settings and therapists.

Nature Medicine is among the most prestigious medical journals in the world. It seldom publishes clinical trials and never before has published a trial of a medication combined with psychotherapy.

I have already been discussing my concerns about this clinical trial in two Medium articles.

Is the New York Times a Shill for Promoters of Psychedelics? Evidence that the newspaper is not sufficiently detached from promoters to provide an open-minded but skeptical.

The MDMA-Assisted Therapy for PTSD Study: What You’ll Get Wrong. Seldom have so many experts had such strong opinions about an open-access drug trial they did not read carefully

The Nature Medicine article is available open access, meaning you can view it for free.

Mitchell, Jennifer M., et al. “MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.” Nature Medicine (2021): 1–9

Clicking on the link takes you to the article on the website, where you can also download a free PDF. However, if you just read the article on the website, the authors are listed like this:

Click on the […] at the website and it expands to the full list of 39 authors.

That number of authors in itself is mindboggling, especially when you consider that 39 is the number of patients assigned to pill placebo who completed the trial. That ratio of authors to patients in a clinical trial is extraordinary.

Check out the list of authors’ affiliations and their specific contributor statements available in the article that justified awarding authorship. You will find some real surprises.

I will touch on some of these details before ending with a bombshell revelation that changed my thinking about this study, raised my already high level of skepticism about it, and pointed me in some new directions in probing the study.

The 39 authors list 25 different affiliations, of which seven are academic medical settings with research capacity. Authors’ academic degrees are not listed in the article, but a Google search reveals few MDs and fewer psychiatrists. Only a few of the MDs list university medical affiliations.

Four authors list the same academic setting as their affiliation. One is the Ph.D. neuroscientist who is the first author. The other authors in that setting are the Ph.D. regulatory affairs coordinator and an internist and an assistant professor MD Ph.D. who is in residence at a nearby Veterans Administration Hospital.

Beyond the other six academic medical settings that are each listed by one author, there are some interesting affiliations.

The largest number of authors (12) are with the MAPS Public Benefit Corporation, San Jose, California. The for-profit corporation will manage sales for prescription MDMA when it is approved by the Food and Drug and Administration. For now, the corporation provides training for therapists as well as:

A team of wonderful night attendants who stay with study participants at the clinic during the required overnight stay following MDMA sessions. The night attendants continue the care and support of participants by delivering or preparing dinner and breakfast, setting up their sleeping arrangements, and remaining available throughout the night should participants need anything at all. During this time, the therapy team and study physician remain on call should there be any problems or concerns.

Most affiliations are for only one or two authors and seem to be private practice settings awaiting approval of psychedelics by the FDA. Their names are suggestive of particular kinds of mystical spa experiences: Zen Therapeutic Solutions, Fluence (defined as a mysterious, magical, or hypnotic power), Nautilus Sanctuary, Wholeness Center, and the San Francisco Insight and Integration Center.

Some of these settings currently — or will in the future — offer spa experiences for people without requiring a diagnosis of a psychiatric disorder. At Aguazul-Bluewater, Inc, one of the authors of the Nature Medicine article offers Rolfing Structural Integration sessions.

In the relaxed biographic sketches provided at their affiliations, a number of authors express the intention to use prescription MDMA not as a formal mental health treatment, but for wellness treatments administered in spa settings specializing in alternative medicine.

Some of the authors of the Nature Medicine articleespouse the use of psychedelics as a transformative experience conceived as an integration of mysticism and neuroscience that is decidedly outside the range of testable and disprovable scientific explanation.

Many of the authors are clinical psychologists who are not quantitative research scientists, but who instead dabble in impressionistic qualitative or mixed-method research related to psychedelics.

I did not see or endorsements of conventional, evidence-based therapies in any of the authors’ personal statements. I found abundant references to the view of personal change as a mystical or spiritual experience somehow involving neuroscience and the brain, but not really spelled out in conventional scientific terms.

It is safe to say that these clinical psychologists do not confine the psychotherapy they offer for PTSD to the manualized treatments with the strongest scientific support, exposure, and cognitive reprocessing therapy. That would be just too stifling and downright boring, especially given the exciting transformative experience that psychotherapy is supposed to provide.

What does it mean to be listed as an author on an article in a highly selective, prestigious medical journal like Nature Medicine?

It is generally understood that authorship on scientific papers requires an intellectual contribution to the conduct of research. In addition, an author must take responsibility for the final version of the paper that will appear in the journal.

I am “only” a clinical psychologist, and I do not have an M.D. Critics might say I am hypocritically pretending to be more scientific than these authors in calling for a more rigorous, i.e., medical approach to this treatment.

The Nature Medicine article presents the case that MDMA is an amazingly effective treatment for PTSD, yet also that it is potentially so dangerous and subject to abuse that it must remain a prescription-only drug delivered under the supervision of a physician.

MDMA has been around for a while and cannot be patented. The Nature Medicine clinical trial tests a packaged delivery system in which the drug augments or facilitates psychotherapy that is said to dramatically reduce the suffering and burden of PTSD.

No one is claiming that taking MDMA by itself is effective in treating PTSD. There is ample evidence to the contrary. So, what is the nature of the psychotherapy that is presumed to allow MDMA to achieve its therapeutic effect?

The psychotherapy offered in this trial is not presumed to be effective in treating PTSD by itself, without MDMA. There is no prior evidence that the particular psychotherapy administered as part of this trial as effective for any clinical problem in any situation.

Although it has been given little attention in the enormous press coverage that has been given to the trial reported in the Nature Medicine paper, a lot depends on the credibility of the psychotherapy provided in the trial. At stake are hundreds of millions of dollars already invested in what is expected to be the multibillion-dollar business of marketing prescription psychedelics plus psychotherapy in a package ensuring their safety and effectiveness as mental health treatment and pleasurable spa experiences.

If MDMA is not patentable, why not patent the package of the drug plus less expensive psychotherapy with greater evidence of efficacy as a mental health treatment, like a modified version of exposure therapy?

Enter the mastermind behind the psychotherapy being offered in this trial

The intellectual responsibility for this parrticular psychotherapy as it is described in the Nature Medicine article largely depends on the nineteenth author, psychiatrist Bessel van der Kolk.

According to the author-contribution statement, Bessel can de Kolk (KvdK) has unrivaled contributions to the article.

BvdK was among the four authors having full access to all of the data in the study and taking responsibility for the integrity of the data and the accuracy of the data analysis. Other contributions attributed to him include the basic design of the study. He was among the authors who collected the data and carried out sponsor oversight of data collection. He was part of the group that carried out statistical analysis and interpretation of data.

He was among the four authors who drafted the original paper. He was a member of the larger group critically revising the paper for important intellectual content.

The two contributions not listed for BvdK are obtaining funding and carrying out supervision and training.

Outside of this trial, BvdK has an enormous following among credentialed and non-credentialed therapists and counselors, as well as a substantial proportion of laypersons who believe their lives have been impacted in a profound way by adversity and trauma. He has sold millions of copies of popular books worldwide, his workshops draw large crowds, and his videos get huge traffic on YouTube.

Yet, many research-oriented mental health professionals consider BvdK a popularizer, not a research-oriented clinician-scientist. Many of us experience enormous frustration with his talks and writing. He promises too much from unproven psychotherapies. Lasting change does not necessarily come with such theatrics as he suggests.

BvdK denigrates scientific evidence and well-established evidence-based therapies. At the same time, he presents unproven somatic therapies and discredited therapies such as tapping and emotional freedom techniques in vivid anecdotes in which miraculous results never fail to be achieved in dramatic, sudden moments of therapist intervention.

BvdK’s best-selling books, like The Body Has its Reasons, present discredited theories like Polyvagal Theory and Mirror Neuron Theory in simplistic terms. Rebuttal and refutation by experts would require long technical explanations that would bore lay audiences to tears and put them to sleep.

Not everyone would agree with me, and certainly not even all evidence-based clinician-researchers. Yet, I think I could muster a considerable consensus that BvdK’s depictions are not to be trusted of the research status of psychotherapies and the scientific status of their presumed basic mechanisms of change.

Such skepticism is just a useful starting point. We might have to revise our opinion with a closer look at the Nature Medicine article, its supplementary materials, and the enormous publicity its authors have so skillfully orchestrated.

Regardless, there are big questions:

How can a drug which is ineffective when simply taken by itself be combined with a psychotherapy without evidence of effectiveness as a standalone treatment to yield results in the treatment of PTSD that have never before been seen?

And

What if the FDA approval of the marketing of the previously illegal street drug Ecstasy as a treatment for PTSD is restricted excuslively to the drug being delivered with a psychotherapy that was developed under the supervision of Bessel van der Kolk?

That would be very strange, but there is a lot of startup funding betting on that possibility. The Franchising of specialty clinics has already begun.

We will have to see how FDA grapples with whether to tie the marketing of a drug to a specific psychotherapy — or is open to continued experimentation with other packages, breaking the monoply of MAPS.

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