Why people lie about COVID

Article Type
Changed
Thu, 10/13/2022 - 14:15

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

Have you ever lied about COVID-19?

Before you get upset, before the “how dare you,” I want you to think carefully.

Did you have COVID-19 (or think you did) and not mention it to someone you were going to be with? Did you tell someone you were taking more COVID precautions than you really were? Did you tell someone you were vaccinated when you weren’t? Have you avoided getting a COVID test even though you knew you should have?

A new study, appearing in JAMA Network Open, suggests that nearly half of people have lied about something to do with COVID. And those are just the people who admit it.

Researchers appreciated the fact that public health interventions in COVID are important but are only as good as the percentage of people who actually abide by them. So, they designed a survey to ask the questions that many people don’t want to hear the answer to.

A total of 1,733 participants – 80% of those invited – responded to the survey. By design, approximately one-third of respondents (477) had already had COVID, one-third (499) were vaccinated and not yet infected, and one-third (509) were unvaccinated and not yet infected.

Of those surveyed, 41.6% admitted that they lied about COVID or didn’t adhere to COVID guidelines - a conservative estimate, if you ask me.

Breaking down some of the results, about 20% of people who previously were infected with COVID said they didn’t mention it when meeting with someone. A similar number said they didn’t tell anyone when they were entering a public place. A bit more concerning to me, roughly 20% reported not disclosing their COVID-positive status when going to a health care provider’s office.

About 10% of those who had not been vaccinated reported lying about their vaccination status. That’s actually less than the 15% of vaccinated people who lied and told someone they weren’t vaccinated.

About 17% of people lied about the need to quarantine, and many more broke quarantine rules.

The authors tried to see if certain personal characteristics predicted people who were more likely to lie about COVID-19–related issues. Turns out there was only one thing that predicted honesty: age.

Older people were more honest about their COVID status and COVID habits. Other factors – gender, education, race, political affiliation, COVID-19 conspiracy beliefs, and where you got your COVID information – did not seem to make much of a difference. Why are older people more honest? Because older people take COVID more seriously. And they should; COVID is more severe in older people.

The problem arises, of course, because people who are at lower risk for COVID complications interact with people at higher risk – and in those situations, honesty matters more.

On the other hand, isn’t lying about COVID stuff inevitable? If you know that a positive test means you can’t go to work, and not going to work means you won’t get paid, might you not be more likely to lie about the test? Or not get the test at all?

The authors explored the reasons for dishonesty and they are fairly broad, ranging from the desire for life to feel normal (more than half of people who lied) to not believing that COVID was real (a whopping 30%). Some of the reasons for lying included:

  • Wanted life to feel normal (50%).
  • Freedom (45%).
  • It’s no one’s business (40%).
  • COVID isn’t real (30%).

In the end, though, we need to realize that public health recommendations are not going to be universally followed, and people may tell us they are following them when, in fact, they are not.

What this adds is another data point to a trend we’ve seen across the course of the pandemic, a shift from collective to individual responsibility. If you can’t be sure what others are doing in regard to COVID, you need to focus on protecting yourself. Perhaps that shift was inevitable. Doesn’t mean we have to like it.

A version of this article first appeared on Medscape.com.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

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This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

Have you ever lied about COVID-19?

Before you get upset, before the “how dare you,” I want you to think carefully.

Did you have COVID-19 (or think you did) and not mention it to someone you were going to be with? Did you tell someone you were taking more COVID precautions than you really were? Did you tell someone you were vaccinated when you weren’t? Have you avoided getting a COVID test even though you knew you should have?

A new study, appearing in JAMA Network Open, suggests that nearly half of people have lied about something to do with COVID. And those are just the people who admit it.

Researchers appreciated the fact that public health interventions in COVID are important but are only as good as the percentage of people who actually abide by them. So, they designed a survey to ask the questions that many people don’t want to hear the answer to.

A total of 1,733 participants – 80% of those invited – responded to the survey. By design, approximately one-third of respondents (477) had already had COVID, one-third (499) were vaccinated and not yet infected, and one-third (509) were unvaccinated and not yet infected.

Of those surveyed, 41.6% admitted that they lied about COVID or didn’t adhere to COVID guidelines - a conservative estimate, if you ask me.

Breaking down some of the results, about 20% of people who previously were infected with COVID said they didn’t mention it when meeting with someone. A similar number said they didn’t tell anyone when they were entering a public place. A bit more concerning to me, roughly 20% reported not disclosing their COVID-positive status when going to a health care provider’s office.

About 10% of those who had not been vaccinated reported lying about their vaccination status. That’s actually less than the 15% of vaccinated people who lied and told someone they weren’t vaccinated.

About 17% of people lied about the need to quarantine, and many more broke quarantine rules.

The authors tried to see if certain personal characteristics predicted people who were more likely to lie about COVID-19–related issues. Turns out there was only one thing that predicted honesty: age.

Older people were more honest about their COVID status and COVID habits. Other factors – gender, education, race, political affiliation, COVID-19 conspiracy beliefs, and where you got your COVID information – did not seem to make much of a difference. Why are older people more honest? Because older people take COVID more seriously. And they should; COVID is more severe in older people.

The problem arises, of course, because people who are at lower risk for COVID complications interact with people at higher risk – and in those situations, honesty matters more.

On the other hand, isn’t lying about COVID stuff inevitable? If you know that a positive test means you can’t go to work, and not going to work means you won’t get paid, might you not be more likely to lie about the test? Or not get the test at all?

The authors explored the reasons for dishonesty and they are fairly broad, ranging from the desire for life to feel normal (more than half of people who lied) to not believing that COVID was real (a whopping 30%). Some of the reasons for lying included:

  • Wanted life to feel normal (50%).
  • Freedom (45%).
  • It’s no one’s business (40%).
  • COVID isn’t real (30%).

In the end, though, we need to realize that public health recommendations are not going to be universally followed, and people may tell us they are following them when, in fact, they are not.

What this adds is another data point to a trend we’ve seen across the course of the pandemic, a shift from collective to individual responsibility. If you can’t be sure what others are doing in regard to COVID, you need to focus on protecting yourself. Perhaps that shift was inevitable. Doesn’t mean we have to like it.

A version of this article first appeared on Medscape.com.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

Have you ever lied about COVID-19?

Before you get upset, before the “how dare you,” I want you to think carefully.

Did you have COVID-19 (or think you did) and not mention it to someone you were going to be with? Did you tell someone you were taking more COVID precautions than you really were? Did you tell someone you were vaccinated when you weren’t? Have you avoided getting a COVID test even though you knew you should have?

A new study, appearing in JAMA Network Open, suggests that nearly half of people have lied about something to do with COVID. And those are just the people who admit it.

Researchers appreciated the fact that public health interventions in COVID are important but are only as good as the percentage of people who actually abide by them. So, they designed a survey to ask the questions that many people don’t want to hear the answer to.

A total of 1,733 participants – 80% of those invited – responded to the survey. By design, approximately one-third of respondents (477) had already had COVID, one-third (499) were vaccinated and not yet infected, and one-third (509) were unvaccinated and not yet infected.

Of those surveyed, 41.6% admitted that they lied about COVID or didn’t adhere to COVID guidelines - a conservative estimate, if you ask me.

Breaking down some of the results, about 20% of people who previously were infected with COVID said they didn’t mention it when meeting with someone. A similar number said they didn’t tell anyone when they were entering a public place. A bit more concerning to me, roughly 20% reported not disclosing their COVID-positive status when going to a health care provider’s office.

About 10% of those who had not been vaccinated reported lying about their vaccination status. That’s actually less than the 15% of vaccinated people who lied and told someone they weren’t vaccinated.

About 17% of people lied about the need to quarantine, and many more broke quarantine rules.

The authors tried to see if certain personal characteristics predicted people who were more likely to lie about COVID-19–related issues. Turns out there was only one thing that predicted honesty: age.

Older people were more honest about their COVID status and COVID habits. Other factors – gender, education, race, political affiliation, COVID-19 conspiracy beliefs, and where you got your COVID information – did not seem to make much of a difference. Why are older people more honest? Because older people take COVID more seriously. And they should; COVID is more severe in older people.

The problem arises, of course, because people who are at lower risk for COVID complications interact with people at higher risk – and in those situations, honesty matters more.

On the other hand, isn’t lying about COVID stuff inevitable? If you know that a positive test means you can’t go to work, and not going to work means you won’t get paid, might you not be more likely to lie about the test? Or not get the test at all?

The authors explored the reasons for dishonesty and they are fairly broad, ranging from the desire for life to feel normal (more than half of people who lied) to not believing that COVID was real (a whopping 30%). Some of the reasons for lying included:

  • Wanted life to feel normal (50%).
  • Freedom (45%).
  • It’s no one’s business (40%).
  • COVID isn’t real (30%).

In the end, though, we need to realize that public health recommendations are not going to be universally followed, and people may tell us they are following them when, in fact, they are not.

What this adds is another data point to a trend we’ve seen across the course of the pandemic, a shift from collective to individual responsibility. If you can’t be sure what others are doing in regard to COVID, you need to focus on protecting yourself. Perhaps that shift was inevitable. Doesn’t mean we have to like it.

A version of this article first appeared on Medscape.com.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

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Like texting and driving: The human cost of AI

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Thu, 10/13/2022 - 13:21

A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we’d known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

Dr. Melissa Walton-Shirley

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.
 

The 2-minute echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn “a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, into an AI-automated process taking 2 minutes, 1 click, with 0% variability.”

Let’s contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She’s shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical corporate chief financial officers will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, “I hope I can sleep in my bed tonight.” Thinking there may be more to the patient’s insomnia than grief-driven anxiety, the sonographer asks her to explain. “I had to sleep in a chair last night because I couldn’t breathe,” Mrs. Smith replies.

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn’t seek attention and is now in heart failure. The consulting cardiologist is alerted. Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here’s a true-life example (some details have been changed to protect the patient’s identity): Mr. Rodriquez was referred for echocardiography because of dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez’s left eye, he replies that he “must have fallen, but can’t remember.” The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted. Instead of chancing a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent annual congress of the European Society of Cardiology, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.
 

 

 

Flawed algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: “Causal AI is the only technology that can reason and make choices like humans do,” the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiological function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019 Science article on racial bias in an algorithm that U.S. health care systems use.  Remedying that bias “would increase the percentage of Black people receiving additional help from 17.7% to 46.5%,” according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don’t live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.

Melissa Walton-Shirley, MD, is a clinical cardiologist in Nashville, Tenn., who has retired from full-time invasive cardiology. She disclosed no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

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A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we’d known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

Dr. Melissa Walton-Shirley

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.
 

The 2-minute echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn “a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, into an AI-automated process taking 2 minutes, 1 click, with 0% variability.”

Let’s contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She’s shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical corporate chief financial officers will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, “I hope I can sleep in my bed tonight.” Thinking there may be more to the patient’s insomnia than grief-driven anxiety, the sonographer asks her to explain. “I had to sleep in a chair last night because I couldn’t breathe,” Mrs. Smith replies.

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn’t seek attention and is now in heart failure. The consulting cardiologist is alerted. Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here’s a true-life example (some details have been changed to protect the patient’s identity): Mr. Rodriquez was referred for echocardiography because of dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez’s left eye, he replies that he “must have fallen, but can’t remember.” The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted. Instead of chancing a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent annual congress of the European Society of Cardiology, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.
 

 

 

Flawed algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: “Causal AI is the only technology that can reason and make choices like humans do,” the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiological function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019 Science article on racial bias in an algorithm that U.S. health care systems use.  Remedying that bias “would increase the percentage of Black people receiving additional help from 17.7% to 46.5%,” according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don’t live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.

Melissa Walton-Shirley, MD, is a clinical cardiologist in Nashville, Tenn., who has retired from full-time invasive cardiology. She disclosed no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we’d known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

Dr. Melissa Walton-Shirley

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.
 

The 2-minute echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn “a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, into an AI-automated process taking 2 minutes, 1 click, with 0% variability.”

Let’s contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She’s shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical corporate chief financial officers will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, “I hope I can sleep in my bed tonight.” Thinking there may be more to the patient’s insomnia than grief-driven anxiety, the sonographer asks her to explain. “I had to sleep in a chair last night because I couldn’t breathe,” Mrs. Smith replies.

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn’t seek attention and is now in heart failure. The consulting cardiologist is alerted. Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here’s a true-life example (some details have been changed to protect the patient’s identity): Mr. Rodriquez was referred for echocardiography because of dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez’s left eye, he replies that he “must have fallen, but can’t remember.” The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted. Instead of chancing a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent annual congress of the European Society of Cardiology, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.
 

 

 

Flawed algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: “Causal AI is the only technology that can reason and make choices like humans do,” the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiological function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019 Science article on racial bias in an algorithm that U.S. health care systems use.  Remedying that bias “would increase the percentage of Black people receiving additional help from 17.7% to 46.5%,” according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don’t live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.

Melissa Walton-Shirley, MD, is a clinical cardiologist in Nashville, Tenn., who has retired from full-time invasive cardiology. She disclosed no relevant conflicts of interest.
 

A version of this article first appeared on Medscape.com.

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Ruminations on health care spending

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Mon, 10/10/2022 - 13:02

What could you do with $18 billion?

I could pay off my mortgage roughly 60,000 times, or take my wife on a never-ending world cruise so we don’t need a mortgage, or at least hire someone to clean my pool regularly so I don’t have to.

A recent report from the OIG found that, in the last 3 years, the Centers for Medicare & Medicaid Services spent $18 billion on drugs for which there’s no proof of significant clinical benefit.

That’s a lot of money on things that may or may not be placebos, some of which are WAY overdue on Food and Drug Administration–mandated efficacy studies. A few have even been on the market so long that they’ve become equally unproven generics.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block

Now, if you put this in the big picture, that immense amount of money is still only 2% of their total spending in health care. Hell, probably at least 2% of my personal spending is on pointless things, too. So, realistically, you could say 98% of CMS spending is on worthwhile care, which is as it should be.

But the bottom line is that $18 billion is still a lot of money if it’s being spent on fruitless treatments. I’m sure it could be better used in many other programs (refunding it to taxpayers comes out to maybe $55 for each of us, which probably isn’t worth the effort).

As pointed out in the movie “Dave,” shoving that kind of money in even a low-yield savings account would generate at least $180 million in interest each year.

That’s a lot of money, too, that could be used for something. Of course, no one in the government thinks that way. That’s why we all loved the movie.

The problem is that the phrase “no proof of significant clinical benefit” doesn’t mean something doesn’t work. It just means we aren’t sure. Some of those people on one of these drugs may be getting benefit – or not. After all, the placebo effect is remarkably strong. But if they are helping someone, who wants to be the one to tell them “we’re not going to pay for this anymore?”

Another issue is this: Let’s say the drugs only work for 10% of the people who take them ($1.8 billion worth), and for the other 90% it’s iffy ($16.2 billion worth), but the latter want to stay on them anyway, just to be sure. Do we cut them? Or just say that $18 billion is too much money when only 10% are being helped, and cut them all off? I’m sure we could use the money elsewhere (see “Dave” above), so let them find a way to work it out with the manufacturer. The greatest good for the greatest number and all that jazz.

I don’t know, either. Health care dollars are finite, and human suffering is infinite. It’s a balancing act that can’t be won. There are no easy answers.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

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What could you do with $18 billion?

I could pay off my mortgage roughly 60,000 times, or take my wife on a never-ending world cruise so we don’t need a mortgage, or at least hire someone to clean my pool regularly so I don’t have to.

A recent report from the OIG found that, in the last 3 years, the Centers for Medicare & Medicaid Services spent $18 billion on drugs for which there’s no proof of significant clinical benefit.

That’s a lot of money on things that may or may not be placebos, some of which are WAY overdue on Food and Drug Administration–mandated efficacy studies. A few have even been on the market so long that they’ve become equally unproven generics.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block

Now, if you put this in the big picture, that immense amount of money is still only 2% of their total spending in health care. Hell, probably at least 2% of my personal spending is on pointless things, too. So, realistically, you could say 98% of CMS spending is on worthwhile care, which is as it should be.

But the bottom line is that $18 billion is still a lot of money if it’s being spent on fruitless treatments. I’m sure it could be better used in many other programs (refunding it to taxpayers comes out to maybe $55 for each of us, which probably isn’t worth the effort).

As pointed out in the movie “Dave,” shoving that kind of money in even a low-yield savings account would generate at least $180 million in interest each year.

That’s a lot of money, too, that could be used for something. Of course, no one in the government thinks that way. That’s why we all loved the movie.

The problem is that the phrase “no proof of significant clinical benefit” doesn’t mean something doesn’t work. It just means we aren’t sure. Some of those people on one of these drugs may be getting benefit – or not. After all, the placebo effect is remarkably strong. But if they are helping someone, who wants to be the one to tell them “we’re not going to pay for this anymore?”

Another issue is this: Let’s say the drugs only work for 10% of the people who take them ($1.8 billion worth), and for the other 90% it’s iffy ($16.2 billion worth), but the latter want to stay on them anyway, just to be sure. Do we cut them? Or just say that $18 billion is too much money when only 10% are being helped, and cut them all off? I’m sure we could use the money elsewhere (see “Dave” above), so let them find a way to work it out with the manufacturer. The greatest good for the greatest number and all that jazz.

I don’t know, either. Health care dollars are finite, and human suffering is infinite. It’s a balancing act that can’t be won. There are no easy answers.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

What could you do with $18 billion?

I could pay off my mortgage roughly 60,000 times, or take my wife on a never-ending world cruise so we don’t need a mortgage, or at least hire someone to clean my pool regularly so I don’t have to.

A recent report from the OIG found that, in the last 3 years, the Centers for Medicare & Medicaid Services spent $18 billion on drugs for which there’s no proof of significant clinical benefit.

That’s a lot of money on things that may or may not be placebos, some of which are WAY overdue on Food and Drug Administration–mandated efficacy studies. A few have even been on the market so long that they’ve become equally unproven generics.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block

Now, if you put this in the big picture, that immense amount of money is still only 2% of their total spending in health care. Hell, probably at least 2% of my personal spending is on pointless things, too. So, realistically, you could say 98% of CMS spending is on worthwhile care, which is as it should be.

But the bottom line is that $18 billion is still a lot of money if it’s being spent on fruitless treatments. I’m sure it could be better used in many other programs (refunding it to taxpayers comes out to maybe $55 for each of us, which probably isn’t worth the effort).

As pointed out in the movie “Dave,” shoving that kind of money in even a low-yield savings account would generate at least $180 million in interest each year.

That’s a lot of money, too, that could be used for something. Of course, no one in the government thinks that way. That’s why we all loved the movie.

The problem is that the phrase “no proof of significant clinical benefit” doesn’t mean something doesn’t work. It just means we aren’t sure. Some of those people on one of these drugs may be getting benefit – or not. After all, the placebo effect is remarkably strong. But if they are helping someone, who wants to be the one to tell them “we’re not going to pay for this anymore?”

Another issue is this: Let’s say the drugs only work for 10% of the people who take them ($1.8 billion worth), and for the other 90% it’s iffy ($16.2 billion worth), but the latter want to stay on them anyway, just to be sure. Do we cut them? Or just say that $18 billion is too much money when only 10% are being helped, and cut them all off? I’m sure we could use the money elsewhere (see “Dave” above), so let them find a way to work it out with the manufacturer. The greatest good for the greatest number and all that jazz.

I don’t know, either. Health care dollars are finite, and human suffering is infinite. It’s a balancing act that can’t be won. There are no easy answers.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

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Clinical psychoeconomics: Accounting for money matters in psychiatric assessment and treatment

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Despite money’s central role in our psychic lives, many trainees – and some seasoned practitioners – skirt around financial issues. Some clinicians confess that inquiring about patients’ finances feels “too personal.” They fear that asking about money could suggest that the clinician is primarily concerned with getting paid. Some clinicians feel that looking into patients’ finances might be unprofessional, outside one’s scope of practice. But it is not.

Dr. Joel Yager

Trainees often receive little guidance concerning money matters in patients’ lives and treatments, considerations we have labeled clinical psychoeconomics. Considerable evidence suggests that financial concerns often provoke emotional distress and dysfunctional behaviors, and directly influence patient’s health care decisions. Financial issues also influence how clinicians view and react to patients.

We have recently reviewed (and illustrated through case vignettes) how money matters might impact psychiatric assessment, case formulation, treatment planning, and ongoing psychiatric treatments including psychotherapies.1 Consider how money affects people’s lives: Money helps people meet multiple practical, psychological, and social needs by enabling them to obtain food, clothing, shelter, other material goods, services, discretionary time, and opportunities. And money strongly influences relationships. Regardless of poverty or wealth, thoughts and behaviors connected to acquiring, possessing, and disposing of money, and feelings accompanying these processes such as greed, neediness, envy, pride, shame, guilt, and self-satisfaction often underly intrapsychic and interpersonal conflicts.

Dr. Jerald Kay

Individuals constantly engage in numerous simultaneous conscious, preconscious, and unconscious neuro-economic trade-offs that determine goals, efforts, and timing. Many are financially influenced. Money influences how virtually all patients seek, receive, and sustain their mental health care including psychotherapy.

Money problems can be associated with insecurity, impotence, feeling unloved, and lack of freedom or subjugation. Individuals may resent how they’re forced to acquire money, and feel shamed or morally injured by their jobs, financial dependence on other family members, public assistance, or their questionable ways of obtaining money.

Impoverished individuals may face choosing between food, housing, medications, and medical care. Domestically abused individuals may reluctantly remain with their abusers, risking physical harm or death rather than face destitution. Some families tolerate severely disabled individuals at home because they rely on their disability checks and caregiver payments. Suicides may turn on how individuals forecast financial repercussions affecting their families. Desires to avoid debt may lead to treatment avoidance.

Individuals with enough money to get by face daily financially related choices involving competing needs, desires, values, and loyalties. They may experience conflicts concerning spending on necessities vs. indulgences or spending on oneself vs. significant others.

Whereas some wealthy individuals may assume unwarranted airs of superiority and entitlement, others may feel guilty about wealth, or fearful that others like them only for their money. Individuals on the receiving end of wealth may feel emotionally and behaviorally manipulated by their benefactors.
 

Assessment

Assessments should consider how financial matters have shaped patients’ early psychological development as well their current lives. How do patients’ emotions, thoughts, and behaviors reflect money matters? What money-related pathologies are evident? What aspects of the patient’s “financial world” seem modifiable?

Financial questions should be posed colloquially. Screeners include: “Where do you live?”, “Who’s in the home?”, “How do you (all) manage financially?”, “What do you all do for a living?”, “How do you make ends meet?”, and “What financial problems are you facing?” Clinicians can quickly learn about patients’ financial self-sufficiencies, individuals for whom they bear financial responsibility, and others they rely on for support, for example, relatives. If patients avoid answering such questions forthrightly, particularly when financial arrangements are “complicated,” clinicians will want to revisit these issues later after establishing a firmer alliance but continue to wonder about the meaning of the patient’s reluctance.

Clinically, money matters manifest intrapsychically or interpersonally in three ways: as explicit conflicts, implicit issues, and unequivocal money-related pathologies. When explicit, patients, families, and couples are fully aware of the conflicts but have difficulty resolving financial disputes. When conflicts are implicit, money problems may be unacknowledged, avoided, denied, or minimized. Conflicts concerning money are often transmitted trans-generationally.

Psychopathological conditions unequivocally linked to money include compulsive shopping, gambling disorders, miserly hoarding, impulse buying, and spending sprees during hypomanic and manic states. Mounting debts may create progressively insurmountable sources of distress. Money can be weaponized to sadistically create enticement, envy, or deprivation. Some monetarily antisocial individuals compromise interpersonal relationships as well as treatments. Individuals with alcohol/substance use disorders may spend so much on substances that little is left for necessities. Financially needy individuals may engage in morally questionable behaviors they might otherwise shun.
 

Case formulation and treatment planning

Incorporating money matters into case formulations entails demonstrating how financial concerns influenced maladaptive development and distort current attitudes, perceptions, and behaviors.

Concurrently, clinicians should acknowledge patients’ reality-based fiscal decisions, appreciating cultural and family value differences concerning how money should be acquired and spent. Since money often determines frequency and duration of treatment visits, clinicians are ethically obligated to discuss with patients what they might expect from different medications and psychotherapies, and their comparative costs.
 

Money matters’ impact on psychotherapies

Money matters often affect transference and countertransference reactions. Some reactions stem from how patients and clinicians compare their own financial situations with those of the other.

To help identify and ameliorate money-related countertransference responses, clinicians can reflect on questions such as: “How comfortable are you with people who are much poorer or richer than you are?” “How comfortable are you with impoverished individuals or with multimillionaires or their children?” And “why?” For trainees, all these reactions should be discussed in supervision.
 

Conclusions

To summarize, four clinical psychoeconomic issues should be routinely assessed and factored into psychiatric case formulations and treatment plans: how financial issues 1) have impacted patients’ psychological development; 2) impact patients’ current lives; 3) are likely to impact access, type, intensity, and duration of treatment visits; and 4) might provoke money-related transference and countertransference concerns.

In advising patients about treatment options, clinicians should discuss each treatment’s relative effectiveness and estimated costs of care. Patients’ decisions will likely be heavily influenced by financial considerations.

Dr. Yager is based in the department of psychiatry, University of Colorado at Denver, Aurora. Dr. Kay is based in the department of psychiatry, Wright State University, Dayton, Ohio. No external funds were received for this project, and the authors have no conflicts to disclose.

Reference

1. Yager J and Kay J. Money matters in psychiatric assessment, case formulation, treatment planning, and ongoing psychotherapy: Clinical psychoeconomics. J Nerv Ment Dis. 2022 Jun 10. doi: 10.1097/NMD.0000000000001552.

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Despite money’s central role in our psychic lives, many trainees – and some seasoned practitioners – skirt around financial issues. Some clinicians confess that inquiring about patients’ finances feels “too personal.” They fear that asking about money could suggest that the clinician is primarily concerned with getting paid. Some clinicians feel that looking into patients’ finances might be unprofessional, outside one’s scope of practice. But it is not.

Dr. Joel Yager

Trainees often receive little guidance concerning money matters in patients’ lives and treatments, considerations we have labeled clinical psychoeconomics. Considerable evidence suggests that financial concerns often provoke emotional distress and dysfunctional behaviors, and directly influence patient’s health care decisions. Financial issues also influence how clinicians view and react to patients.

We have recently reviewed (and illustrated through case vignettes) how money matters might impact psychiatric assessment, case formulation, treatment planning, and ongoing psychiatric treatments including psychotherapies.1 Consider how money affects people’s lives: Money helps people meet multiple practical, psychological, and social needs by enabling them to obtain food, clothing, shelter, other material goods, services, discretionary time, and opportunities. And money strongly influences relationships. Regardless of poverty or wealth, thoughts and behaviors connected to acquiring, possessing, and disposing of money, and feelings accompanying these processes such as greed, neediness, envy, pride, shame, guilt, and self-satisfaction often underly intrapsychic and interpersonal conflicts.

Dr. Jerald Kay

Individuals constantly engage in numerous simultaneous conscious, preconscious, and unconscious neuro-economic trade-offs that determine goals, efforts, and timing. Many are financially influenced. Money influences how virtually all patients seek, receive, and sustain their mental health care including psychotherapy.

Money problems can be associated with insecurity, impotence, feeling unloved, and lack of freedom or subjugation. Individuals may resent how they’re forced to acquire money, and feel shamed or morally injured by their jobs, financial dependence on other family members, public assistance, or their questionable ways of obtaining money.

Impoverished individuals may face choosing between food, housing, medications, and medical care. Domestically abused individuals may reluctantly remain with their abusers, risking physical harm or death rather than face destitution. Some families tolerate severely disabled individuals at home because they rely on their disability checks and caregiver payments. Suicides may turn on how individuals forecast financial repercussions affecting their families. Desires to avoid debt may lead to treatment avoidance.

Individuals with enough money to get by face daily financially related choices involving competing needs, desires, values, and loyalties. They may experience conflicts concerning spending on necessities vs. indulgences or spending on oneself vs. significant others.

Whereas some wealthy individuals may assume unwarranted airs of superiority and entitlement, others may feel guilty about wealth, or fearful that others like them only for their money. Individuals on the receiving end of wealth may feel emotionally and behaviorally manipulated by their benefactors.
 

Assessment

Assessments should consider how financial matters have shaped patients’ early psychological development as well their current lives. How do patients’ emotions, thoughts, and behaviors reflect money matters? What money-related pathologies are evident? What aspects of the patient’s “financial world” seem modifiable?

Financial questions should be posed colloquially. Screeners include: “Where do you live?”, “Who’s in the home?”, “How do you (all) manage financially?”, “What do you all do for a living?”, “How do you make ends meet?”, and “What financial problems are you facing?” Clinicians can quickly learn about patients’ financial self-sufficiencies, individuals for whom they bear financial responsibility, and others they rely on for support, for example, relatives. If patients avoid answering such questions forthrightly, particularly when financial arrangements are “complicated,” clinicians will want to revisit these issues later after establishing a firmer alliance but continue to wonder about the meaning of the patient’s reluctance.

Clinically, money matters manifest intrapsychically or interpersonally in three ways: as explicit conflicts, implicit issues, and unequivocal money-related pathologies. When explicit, patients, families, and couples are fully aware of the conflicts but have difficulty resolving financial disputes. When conflicts are implicit, money problems may be unacknowledged, avoided, denied, or minimized. Conflicts concerning money are often transmitted trans-generationally.

Psychopathological conditions unequivocally linked to money include compulsive shopping, gambling disorders, miserly hoarding, impulse buying, and spending sprees during hypomanic and manic states. Mounting debts may create progressively insurmountable sources of distress. Money can be weaponized to sadistically create enticement, envy, or deprivation. Some monetarily antisocial individuals compromise interpersonal relationships as well as treatments. Individuals with alcohol/substance use disorders may spend so much on substances that little is left for necessities. Financially needy individuals may engage in morally questionable behaviors they might otherwise shun.
 

Case formulation and treatment planning

Incorporating money matters into case formulations entails demonstrating how financial concerns influenced maladaptive development and distort current attitudes, perceptions, and behaviors.

Concurrently, clinicians should acknowledge patients’ reality-based fiscal decisions, appreciating cultural and family value differences concerning how money should be acquired and spent. Since money often determines frequency and duration of treatment visits, clinicians are ethically obligated to discuss with patients what they might expect from different medications and psychotherapies, and their comparative costs.
 

Money matters’ impact on psychotherapies

Money matters often affect transference and countertransference reactions. Some reactions stem from how patients and clinicians compare their own financial situations with those of the other.

To help identify and ameliorate money-related countertransference responses, clinicians can reflect on questions such as: “How comfortable are you with people who are much poorer or richer than you are?” “How comfortable are you with impoverished individuals or with multimillionaires or their children?” And “why?” For trainees, all these reactions should be discussed in supervision.
 

Conclusions

To summarize, four clinical psychoeconomic issues should be routinely assessed and factored into psychiatric case formulations and treatment plans: how financial issues 1) have impacted patients’ psychological development; 2) impact patients’ current lives; 3) are likely to impact access, type, intensity, and duration of treatment visits; and 4) might provoke money-related transference and countertransference concerns.

In advising patients about treatment options, clinicians should discuss each treatment’s relative effectiveness and estimated costs of care. Patients’ decisions will likely be heavily influenced by financial considerations.

Dr. Yager is based in the department of psychiatry, University of Colorado at Denver, Aurora. Dr. Kay is based in the department of psychiatry, Wright State University, Dayton, Ohio. No external funds were received for this project, and the authors have no conflicts to disclose.

Reference

1. Yager J and Kay J. Money matters in psychiatric assessment, case formulation, treatment planning, and ongoing psychotherapy: Clinical psychoeconomics. J Nerv Ment Dis. 2022 Jun 10. doi: 10.1097/NMD.0000000000001552.

Despite money’s central role in our psychic lives, many trainees – and some seasoned practitioners – skirt around financial issues. Some clinicians confess that inquiring about patients’ finances feels “too personal.” They fear that asking about money could suggest that the clinician is primarily concerned with getting paid. Some clinicians feel that looking into patients’ finances might be unprofessional, outside one’s scope of practice. But it is not.

Dr. Joel Yager

Trainees often receive little guidance concerning money matters in patients’ lives and treatments, considerations we have labeled clinical psychoeconomics. Considerable evidence suggests that financial concerns often provoke emotional distress and dysfunctional behaviors, and directly influence patient’s health care decisions. Financial issues also influence how clinicians view and react to patients.

We have recently reviewed (and illustrated through case vignettes) how money matters might impact psychiatric assessment, case formulation, treatment planning, and ongoing psychiatric treatments including psychotherapies.1 Consider how money affects people’s lives: Money helps people meet multiple practical, psychological, and social needs by enabling them to obtain food, clothing, shelter, other material goods, services, discretionary time, and opportunities. And money strongly influences relationships. Regardless of poverty or wealth, thoughts and behaviors connected to acquiring, possessing, and disposing of money, and feelings accompanying these processes such as greed, neediness, envy, pride, shame, guilt, and self-satisfaction often underly intrapsychic and interpersonal conflicts.

Dr. Jerald Kay

Individuals constantly engage in numerous simultaneous conscious, preconscious, and unconscious neuro-economic trade-offs that determine goals, efforts, and timing. Many are financially influenced. Money influences how virtually all patients seek, receive, and sustain their mental health care including psychotherapy.

Money problems can be associated with insecurity, impotence, feeling unloved, and lack of freedom or subjugation. Individuals may resent how they’re forced to acquire money, and feel shamed or morally injured by their jobs, financial dependence on other family members, public assistance, or their questionable ways of obtaining money.

Impoverished individuals may face choosing between food, housing, medications, and medical care. Domestically abused individuals may reluctantly remain with their abusers, risking physical harm or death rather than face destitution. Some families tolerate severely disabled individuals at home because they rely on their disability checks and caregiver payments. Suicides may turn on how individuals forecast financial repercussions affecting their families. Desires to avoid debt may lead to treatment avoidance.

Individuals with enough money to get by face daily financially related choices involving competing needs, desires, values, and loyalties. They may experience conflicts concerning spending on necessities vs. indulgences or spending on oneself vs. significant others.

Whereas some wealthy individuals may assume unwarranted airs of superiority and entitlement, others may feel guilty about wealth, or fearful that others like them only for their money. Individuals on the receiving end of wealth may feel emotionally and behaviorally manipulated by their benefactors.
 

Assessment

Assessments should consider how financial matters have shaped patients’ early psychological development as well their current lives. How do patients’ emotions, thoughts, and behaviors reflect money matters? What money-related pathologies are evident? What aspects of the patient’s “financial world” seem modifiable?

Financial questions should be posed colloquially. Screeners include: “Where do you live?”, “Who’s in the home?”, “How do you (all) manage financially?”, “What do you all do for a living?”, “How do you make ends meet?”, and “What financial problems are you facing?” Clinicians can quickly learn about patients’ financial self-sufficiencies, individuals for whom they bear financial responsibility, and others they rely on for support, for example, relatives. If patients avoid answering such questions forthrightly, particularly when financial arrangements are “complicated,” clinicians will want to revisit these issues later after establishing a firmer alliance but continue to wonder about the meaning of the patient’s reluctance.

Clinically, money matters manifest intrapsychically or interpersonally in three ways: as explicit conflicts, implicit issues, and unequivocal money-related pathologies. When explicit, patients, families, and couples are fully aware of the conflicts but have difficulty resolving financial disputes. When conflicts are implicit, money problems may be unacknowledged, avoided, denied, or minimized. Conflicts concerning money are often transmitted trans-generationally.

Psychopathological conditions unequivocally linked to money include compulsive shopping, gambling disorders, miserly hoarding, impulse buying, and spending sprees during hypomanic and manic states. Mounting debts may create progressively insurmountable sources of distress. Money can be weaponized to sadistically create enticement, envy, or deprivation. Some monetarily antisocial individuals compromise interpersonal relationships as well as treatments. Individuals with alcohol/substance use disorders may spend so much on substances that little is left for necessities. Financially needy individuals may engage in morally questionable behaviors they might otherwise shun.
 

Case formulation and treatment planning

Incorporating money matters into case formulations entails demonstrating how financial concerns influenced maladaptive development and distort current attitudes, perceptions, and behaviors.

Concurrently, clinicians should acknowledge patients’ reality-based fiscal decisions, appreciating cultural and family value differences concerning how money should be acquired and spent. Since money often determines frequency and duration of treatment visits, clinicians are ethically obligated to discuss with patients what they might expect from different medications and psychotherapies, and their comparative costs.
 

Money matters’ impact on psychotherapies

Money matters often affect transference and countertransference reactions. Some reactions stem from how patients and clinicians compare their own financial situations with those of the other.

To help identify and ameliorate money-related countertransference responses, clinicians can reflect on questions such as: “How comfortable are you with people who are much poorer or richer than you are?” “How comfortable are you with impoverished individuals or with multimillionaires or their children?” And “why?” For trainees, all these reactions should be discussed in supervision.
 

Conclusions

To summarize, four clinical psychoeconomic issues should be routinely assessed and factored into psychiatric case formulations and treatment plans: how financial issues 1) have impacted patients’ psychological development; 2) impact patients’ current lives; 3) are likely to impact access, type, intensity, and duration of treatment visits; and 4) might provoke money-related transference and countertransference concerns.

In advising patients about treatment options, clinicians should discuss each treatment’s relative effectiveness and estimated costs of care. Patients’ decisions will likely be heavily influenced by financial considerations.

Dr. Yager is based in the department of psychiatry, University of Colorado at Denver, Aurora. Dr. Kay is based in the department of psychiatry, Wright State University, Dayton, Ohio. No external funds were received for this project, and the authors have no conflicts to disclose.

Reference

1. Yager J and Kay J. Money matters in psychiatric assessment, case formulation, treatment planning, and ongoing psychotherapy: Clinical psychoeconomics. J Nerv Ment Dis. 2022 Jun 10. doi: 10.1097/NMD.0000000000001552.

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The price we pay for an MD

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It is no secret that medical school is expensive. Depending on where in the world you live, the cost of a medical degree varies. In the United States, it is well known that medical students end up with an average of $241,600 in debt after at least 8 years of education; attending a public, private, Ivy League or non–Ivy League school may cause this to differ among students.

In the United Kingdom, however, the true cost of medical training isn’t as obvious. All students pay the same amount of tuition, which is usually paid for by a government loan for the entirety of their course. For those who need it, a maintenance loan is also available for living expenses. Naturally, those from lower income households receive higher maintenance loans and therefore, have a higher debt burden by the end of their studies – debt you don’t think about until your first real paycheck post medical school. (It is also important to note that these loans are completely optional – throughout my time in medical school, I’ve encountered students who didn’t need all or any of their student loans to pay for their medical school tuition or living expenses.)

The real cost, however, the one we have to live with everyday as students, comes from expenses that we were not warned about when embarking on our journey through medical school – for example, the cost of a stethoscope, revision resources, transport, and housing. In addition, as the commitment of a medical degree intensifies, there is less and less time for students to work-part time outside of their studies, meaning less income coming in while expenses increase and student loans accumulate interest.

Furthermore, it is common knowledge that a higher proportion of students from affluent backgrounds are accepted into medical school and that socioeconomic status and one’s finances create a huge disparity in achievement and general well-being during medical school. Indeed, studies show that higher levels of debt are negatively correlated with mental well-being and academic performance; students from lower socioeconomic backgrounds have higher debts and as a result, worry more about money.

Four years into my medical education, I have experienced and now understand the financial strain of a medical degree. The path to becoming a doctor truly is one of life-long sacrifice, so why doesn’t our society look after those who make it their life’s work to look after them? It is incredibly unfortunate that there is a lack of financial support and assistance for medical trainees, especially those from lower socioeconomic backgrounds. In fact, according to a BMJ study, about 5% of students were considering dropping out of medical school because of financial hardship alone and have cut back on simple living essentials such as heating and food.

Unfortunately, these are the students that are more representative of the patient population; the average patient that we see is not one had that a private school education or had affluent parents. Although more people from diverse backgrounds are enrolling in medical school, finances act as yet another barrier preventing them from completing this degree; such factors are why we see such limited diversity in medicine.

Talking about finances appears to be a taboo in the medical field, but doing so is important, for it not only raises awareness and creates a voice for those 5% of students who are struggling financially but also helps premed students have a realistic understanding of the financial sacrifice of pursuing medicine, allowing them to make more informed choices about their future careers. In the meantime, as we create this new culture, it will be important for institutions to consider supporting students financially through bursaries and scholarships (and reducing tuition prices) throughout their time at university. In this way, we can create a more equitable and encouraging environments for all medical trainees.

Ms. Ntorinkansah is a medical student at the University of Nottingham (England). She reported no conflicts of interest.



A version of this article first appeared on Medscape.com.

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It is no secret that medical school is expensive. Depending on where in the world you live, the cost of a medical degree varies. In the United States, it is well known that medical students end up with an average of $241,600 in debt after at least 8 years of education; attending a public, private, Ivy League or non–Ivy League school may cause this to differ among students.

In the United Kingdom, however, the true cost of medical training isn’t as obvious. All students pay the same amount of tuition, which is usually paid for by a government loan for the entirety of their course. For those who need it, a maintenance loan is also available for living expenses. Naturally, those from lower income households receive higher maintenance loans and therefore, have a higher debt burden by the end of their studies – debt you don’t think about until your first real paycheck post medical school. (It is also important to note that these loans are completely optional – throughout my time in medical school, I’ve encountered students who didn’t need all or any of their student loans to pay for their medical school tuition or living expenses.)

The real cost, however, the one we have to live with everyday as students, comes from expenses that we were not warned about when embarking on our journey through medical school – for example, the cost of a stethoscope, revision resources, transport, and housing. In addition, as the commitment of a medical degree intensifies, there is less and less time for students to work-part time outside of their studies, meaning less income coming in while expenses increase and student loans accumulate interest.

Furthermore, it is common knowledge that a higher proportion of students from affluent backgrounds are accepted into medical school and that socioeconomic status and one’s finances create a huge disparity in achievement and general well-being during medical school. Indeed, studies show that higher levels of debt are negatively correlated with mental well-being and academic performance; students from lower socioeconomic backgrounds have higher debts and as a result, worry more about money.

Four years into my medical education, I have experienced and now understand the financial strain of a medical degree. The path to becoming a doctor truly is one of life-long sacrifice, so why doesn’t our society look after those who make it their life’s work to look after them? It is incredibly unfortunate that there is a lack of financial support and assistance for medical trainees, especially those from lower socioeconomic backgrounds. In fact, according to a BMJ study, about 5% of students were considering dropping out of medical school because of financial hardship alone and have cut back on simple living essentials such as heating and food.

Unfortunately, these are the students that are more representative of the patient population; the average patient that we see is not one had that a private school education or had affluent parents. Although more people from diverse backgrounds are enrolling in medical school, finances act as yet another barrier preventing them from completing this degree; such factors are why we see such limited diversity in medicine.

Talking about finances appears to be a taboo in the medical field, but doing so is important, for it not only raises awareness and creates a voice for those 5% of students who are struggling financially but also helps premed students have a realistic understanding of the financial sacrifice of pursuing medicine, allowing them to make more informed choices about their future careers. In the meantime, as we create this new culture, it will be important for institutions to consider supporting students financially through bursaries and scholarships (and reducing tuition prices) throughout their time at university. In this way, we can create a more equitable and encouraging environments for all medical trainees.

Ms. Ntorinkansah is a medical student at the University of Nottingham (England). She reported no conflicts of interest.



A version of this article first appeared on Medscape.com.

 

It is no secret that medical school is expensive. Depending on where in the world you live, the cost of a medical degree varies. In the United States, it is well known that medical students end up with an average of $241,600 in debt after at least 8 years of education; attending a public, private, Ivy League or non–Ivy League school may cause this to differ among students.

In the United Kingdom, however, the true cost of medical training isn’t as obvious. All students pay the same amount of tuition, which is usually paid for by a government loan for the entirety of their course. For those who need it, a maintenance loan is also available for living expenses. Naturally, those from lower income households receive higher maintenance loans and therefore, have a higher debt burden by the end of their studies – debt you don’t think about until your first real paycheck post medical school. (It is also important to note that these loans are completely optional – throughout my time in medical school, I’ve encountered students who didn’t need all or any of their student loans to pay for their medical school tuition or living expenses.)

The real cost, however, the one we have to live with everyday as students, comes from expenses that we were not warned about when embarking on our journey through medical school – for example, the cost of a stethoscope, revision resources, transport, and housing. In addition, as the commitment of a medical degree intensifies, there is less and less time for students to work-part time outside of their studies, meaning less income coming in while expenses increase and student loans accumulate interest.

Furthermore, it is common knowledge that a higher proportion of students from affluent backgrounds are accepted into medical school and that socioeconomic status and one’s finances create a huge disparity in achievement and general well-being during medical school. Indeed, studies show that higher levels of debt are negatively correlated with mental well-being and academic performance; students from lower socioeconomic backgrounds have higher debts and as a result, worry more about money.

Four years into my medical education, I have experienced and now understand the financial strain of a medical degree. The path to becoming a doctor truly is one of life-long sacrifice, so why doesn’t our society look after those who make it their life’s work to look after them? It is incredibly unfortunate that there is a lack of financial support and assistance for medical trainees, especially those from lower socioeconomic backgrounds. In fact, according to a BMJ study, about 5% of students were considering dropping out of medical school because of financial hardship alone and have cut back on simple living essentials such as heating and food.

Unfortunately, these are the students that are more representative of the patient population; the average patient that we see is not one had that a private school education or had affluent parents. Although more people from diverse backgrounds are enrolling in medical school, finances act as yet another barrier preventing them from completing this degree; such factors are why we see such limited diversity in medicine.

Talking about finances appears to be a taboo in the medical field, but doing so is important, for it not only raises awareness and creates a voice for those 5% of students who are struggling financially but also helps premed students have a realistic understanding of the financial sacrifice of pursuing medicine, allowing them to make more informed choices about their future careers. In the meantime, as we create this new culture, it will be important for institutions to consider supporting students financially through bursaries and scholarships (and reducing tuition prices) throughout their time at university. In this way, we can create a more equitable and encouraging environments for all medical trainees.

Ms. Ntorinkansah is a medical student at the University of Nottingham (England). She reported no conflicts of interest.



A version of this article first appeared on Medscape.com.

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Is another COVID-19 booster really needed?

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Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)

In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

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Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)

In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

 

Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question “Is another jab really needed?” (The short answer is a firm “yes,” of course.)

In what we could call the “chronic” phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It’s the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn’t mean that those who have their vaccination records up to date (which included a booster probably earlier in 2022) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this roughly 10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it’s easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it’s also an age issue. On the basis of different studies of the most common ages of admission, the cutoff point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defenses, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Dr. Macip is associate professor, department of molecular and cellular biology, University of Leicester (England). He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

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ESMO’s new focus on cancer prevention

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Wed, 10/05/2022 - 14:07

This transcript has been edited for clarity.

John Whyte, MD: Welcome, everyone. I’m Dr John Whyte. I’m the chief medical officer at WebMD, and I’m joined today by Fabrice André. He is the chair of the scientific committee at the European Society for Medical Oncology, where we are today in Paris, France. Bonjour, Fabrice.

So, remind our viewers: What is ESMO? What does it do? And why is it so important?

Fabrice André, MD, PhD: First ESMO, is a scientific society – a member-based organization with around 25,000 members.

Dr. Whyte: Equivalent to ASCO (American Society of Clinical Oncology) in the United States, correct?

Dr. André: It has members worldwide, from all over the world. And it aims at disseminating science, educating. The name is European, so it has some roots in Europe; but it is really a global organization for education, dissemination, and also more and more to generate frameworks for the standards of treatment and the common terminology for healthcare professionals to better care for patients.

Dr. Whyte: What are you most excited by at this conference in terms of the innovations that are being discussed?

Dr. André: Today we are at ESMO 2022 in Paris, with 28,000 people registered and the vast majority on site, and what has been the editorial line – the tagline – for the scientific committee is “understand the disease to better treat the patient.” This is extremely important; all of the educational program is built on this tagline, meaning that we need to understand what are the mechanisms of cancer progression? What are the determinants of outcomes if we want to integrate all the wealth of innovation that is coming?

So, then, what are the new things? In the Presidential Symposium, where we usually have the very new things, we will have very important presentations on the role of pollution on cancer and the biological mechanism that induces cancer. Why is it important? First, it has impact on public health. But also, it’s important because, for us, it’s raising the signal that the oncology community must start to invest in this field of prevention.

Dr. Whyte: I was at your booth, by the way, the ESMO booth here, and you have two bicycles, which impressed me. Nobody was on them, I might point out, but the focus was on prevention. But let’s also address how historically, the academic community, the scientific community hasn’t really been focused on prevention. It’s about treatment. So it’s fascinating that you’re talking about prevention, because usually we talk about precision medicine, right? We talk about checkpoint inhibitors; we talk about immunomodulators. And here you’re saying, “Hey, John, we need to understand how we prevent cancer,” which is really a misnomer in a way, because there are many different diseases. Would you agree with that?

Dr. André: I fully agree with you. But what is the premise we are trying to address here? The premise is that prevention has always been very low in the agenda of international conferences. And we think we want to give the signal that it’s really time now that clinical infrastructure, hospitals, invest in this field, create teams dedicated to prevention, new structures for prevention. Why? Because we are discovering step by step that it could be that some drugs we use for patients with cancer could also be developed in the field of prevention. And for this, we need the oncologists. So, more and more, our conviction is that it is the oncology community that will transform the field of prevention, and we need to invest now. Having said that, we have two very important abstracts on this question. The other one is about early cancer detection. But of course, we have our traditional session on immunotherapeutics, precision medicine, and all the wealth of randomized trials. And so in this field, for patients with cancer, what is the new information?

Dr. Whyte: We have this whole continuum. So you talk about prevention – how much cancer is preventable? Eighty percent? Seventy percent? What do you estimate?

Dr. André: You know, I’m also a scientist. So as a scientist, I will say that there is no limit for this question. No, the only limit is the knowledge.

Dr. Whyte: Well, there is some inherited mutation, so we do know that.

Dr. André: We can just go to the current status – what we know now – but I don’t see why we would put some limit on how much we can prevent cancer. But indeed, so far, what are the risk factors? Genetics, hereditary cancer, all habits, and we know them. It’s about tobacco, alcohol, sun, some sexual behavior, etc., that indeed account. In France, we say that around 40% of cancer could be preventable.

Dr. Whyte: More and more, we learn about the issues of gout, other inflammatory diseases; it can have an association, but then we have early screening as well. So, if we’re on this continuum, how excited are you by what’s happening with liquid biopsies, with other testing? Because if we can get a cancer instead of at 500,000 cells at the time of imaging, at 10 or 50 cells, while there are fragments, that’s revolutionary, isn’t it?

Dr. André: I fully agree with you. We will have an important trial presented during ESMO that is the first prospective trial testing the device called Galleri, a tool for early cancer detection based on ctDNA (circulating tumor DNA) analysis by methylation pattern.

Dr. Whyte: General screening of the population or a more tailored population with certain indications? Because right now, most of those have focused on a limited population or are used for patients who already have a cancer, and testing that way – you think it’s going to be broader?

Dr. André: What this trial is investigating is in participants who do not have cancer, 6,000 participants ...

Dr. Whyte: Pas de tout? No cancer at all?

Dr. André: No cancer.

Dr. Whyte: No family history?

Dr. André: They can have family history, but no detectable cancer – can ctDNA analysis detect cancer? And the answer is, indeed, there is around 1% positivity, and around 40% of them, indeed, had cancer. So why is it important? Because it’s really a landmark prospective trial that is telling us that a device based on ctDNA can detect cancer at early stage. Then, how many cancers? What percentage?

Dr. Whyte: Which type of cancer?

Dr. André: And is it going to have an impact on outcome? And for all the questions, we don’t have the answer here. But the answer we have here today is that with this device, done prospectively, you can detect some cancer that would not be detectable without symptoms.

Dr. Whyte: It’s only going to get better, too.

Dr. André: Yeah. So then the next step is improving technology, integrating this technology with other ones we already have, in order to increase the percentage of patients in which we detect cancer at an earlier stage.

Dr. Whyte: What about pancreatic cancer, cancers we can’t detect through screening? People forget that most cancers cannot be detected through screening, so we need better tools. We do know that there are inherited mutations. Those really aren’t preventable in many ways; the goal is to get them early. So then we move to treatments, and you talked about precision medicine. What excites you about what’s going on these days at ESMO right now.

Dr. André: We have many trials on precision medicine. We will have two randomized trials that investigate two new targets; one is gamma secretase inhibitor. So, it’s a first-in-class, first time we even hear about this target at a clinical conference. And the second highly expected trial is a clinical trial in patients with metastatic lung cancer, KRAS mutated, testing sotorasib, which is a KRAS inhibitor, and showing the magnitude of improvement associated with sotorasib. The trial is positive, and it improved PFS [progression-free survival] in these patients. So these are two new targets that are validated at this conference.

 

 

Then, if we go on another topic of genomics, there is a question that is extremely important: Can we define patients who present an outlier sensitivity to immunotherapeutics? There will be one trial presented in the Presidential Symposium of immunotherapeutics in patients with colon cancer and microsatellite instability (MSI), showing that a few weeks of immunotherapeutics followed by surgery can cure patients. Why is it important? It’s important because we are all facing a shortage in the healthcare workforce. We have fewer nurses, fewer doctors, and we all have issues of sustainability. So, really now is the time to think about precision medicine, how precision medicine, by identifying outlier responders, can decrease the amount of resources we need to cure a patient. And this trial on immunotherapeutics, guided by genomics, is exactly this point: 8 weeks of treatment to cure a patient.

Dr. Whyte: Do you think there’s going to be a cure for cancer 10 years from now?

Dr. André: What I’m convinced of is that, in the 10 years that are coming, we are going step by step; we’re going to continue to increase the life expectancy of patients with cancer.

Dr. Whyte: And quality of life too, right?

Dr. André: Quality of life is a major issue. We had today a keynote on digital medicine and how ePRO (electronic patient-reported outcomes) can help the patient to really decrease the burden of symptoms. Quality of life is, of course, extremely important because of the very high number of patients who are cured of cancer; we need to decrease the burden of symptom in patients.

Dr. Whyte: And even though cancer rates are going down in most areas of the world, we still globally have millions of deaths from cancer every year. And sometimes people forget that, because they hear about some of the innovations. But I want to end with this: Are we investing enough in cancer care? Because let’s be honest – there are other diseases that we also need to spend time on. Cardiovascular disease is a global burden; infectious disease is a global burden. Are governments, are industries spending enough on cancer research and development?

Dr. André: Well, we can always claim for more, no? This is how everyone is trying to be, I think. But the reality is that we are living in a world where we have limited resources. I think what is more important for me is to be sure that any euro or dollar invested in cancer research is well used and generates an impact for patients. That is the most important, I think.

Dr. Whyte: And that’s why outcomes are so important in this research.

Dr. André: My conviction is that we have the tools, meaning the knowledge, the biotechnology, to really go the next step in terms of improving outcomes for patients. And for this, we now need clinical trials and translational research, but the tools, meaning basic science, basic knowledge, biotechnology – the basement for progress is here. We need now to transform this into direct impact for the patient. But I would not like to finish by saying we need more money in the field; what we need are people who can transform one euro, one dollar into concrete and measurable advances.

Dr. Whyte: We’re going to need more time on another day because I want to ask you about diversity in clinical trials, how important that is. I want to ask you about pediatric cancers; there are a whole bunch of things that I want to talk to you about. So hopefully we’ll find more time when we’re not at a big international conference such as ESMO. So, Dr Fabrice André, I want to thank you for taking time today.

Dr. André: Thank you and have a nice day.

Dr. Whyte: Stay tuned for a future discussion with Dr André on more about where we’re going in terms of cancer research and development. Thanks for watching, everyone.

A version of this article first appeared on Medscape.com.

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This transcript has been edited for clarity.

John Whyte, MD: Welcome, everyone. I’m Dr John Whyte. I’m the chief medical officer at WebMD, and I’m joined today by Fabrice André. He is the chair of the scientific committee at the European Society for Medical Oncology, where we are today in Paris, France. Bonjour, Fabrice.

So, remind our viewers: What is ESMO? What does it do? And why is it so important?

Fabrice André, MD, PhD: First ESMO, is a scientific society – a member-based organization with around 25,000 members.

Dr. Whyte: Equivalent to ASCO (American Society of Clinical Oncology) in the United States, correct?

Dr. André: It has members worldwide, from all over the world. And it aims at disseminating science, educating. The name is European, so it has some roots in Europe; but it is really a global organization for education, dissemination, and also more and more to generate frameworks for the standards of treatment and the common terminology for healthcare professionals to better care for patients.

Dr. Whyte: What are you most excited by at this conference in terms of the innovations that are being discussed?

Dr. André: Today we are at ESMO 2022 in Paris, with 28,000 people registered and the vast majority on site, and what has been the editorial line – the tagline – for the scientific committee is “understand the disease to better treat the patient.” This is extremely important; all of the educational program is built on this tagline, meaning that we need to understand what are the mechanisms of cancer progression? What are the determinants of outcomes if we want to integrate all the wealth of innovation that is coming?

So, then, what are the new things? In the Presidential Symposium, where we usually have the very new things, we will have very important presentations on the role of pollution on cancer and the biological mechanism that induces cancer. Why is it important? First, it has impact on public health. But also, it’s important because, for us, it’s raising the signal that the oncology community must start to invest in this field of prevention.

Dr. Whyte: I was at your booth, by the way, the ESMO booth here, and you have two bicycles, which impressed me. Nobody was on them, I might point out, but the focus was on prevention. But let’s also address how historically, the academic community, the scientific community hasn’t really been focused on prevention. It’s about treatment. So it’s fascinating that you’re talking about prevention, because usually we talk about precision medicine, right? We talk about checkpoint inhibitors; we talk about immunomodulators. And here you’re saying, “Hey, John, we need to understand how we prevent cancer,” which is really a misnomer in a way, because there are many different diseases. Would you agree with that?

Dr. André: I fully agree with you. But what is the premise we are trying to address here? The premise is that prevention has always been very low in the agenda of international conferences. And we think we want to give the signal that it’s really time now that clinical infrastructure, hospitals, invest in this field, create teams dedicated to prevention, new structures for prevention. Why? Because we are discovering step by step that it could be that some drugs we use for patients with cancer could also be developed in the field of prevention. And for this, we need the oncologists. So, more and more, our conviction is that it is the oncology community that will transform the field of prevention, and we need to invest now. Having said that, we have two very important abstracts on this question. The other one is about early cancer detection. But of course, we have our traditional session on immunotherapeutics, precision medicine, and all the wealth of randomized trials. And so in this field, for patients with cancer, what is the new information?

Dr. Whyte: We have this whole continuum. So you talk about prevention – how much cancer is preventable? Eighty percent? Seventy percent? What do you estimate?

Dr. André: You know, I’m also a scientist. So as a scientist, I will say that there is no limit for this question. No, the only limit is the knowledge.

Dr. Whyte: Well, there is some inherited mutation, so we do know that.

Dr. André: We can just go to the current status – what we know now – but I don’t see why we would put some limit on how much we can prevent cancer. But indeed, so far, what are the risk factors? Genetics, hereditary cancer, all habits, and we know them. It’s about tobacco, alcohol, sun, some sexual behavior, etc., that indeed account. In France, we say that around 40% of cancer could be preventable.

Dr. Whyte: More and more, we learn about the issues of gout, other inflammatory diseases; it can have an association, but then we have early screening as well. So, if we’re on this continuum, how excited are you by what’s happening with liquid biopsies, with other testing? Because if we can get a cancer instead of at 500,000 cells at the time of imaging, at 10 or 50 cells, while there are fragments, that’s revolutionary, isn’t it?

Dr. André: I fully agree with you. We will have an important trial presented during ESMO that is the first prospective trial testing the device called Galleri, a tool for early cancer detection based on ctDNA (circulating tumor DNA) analysis by methylation pattern.

Dr. Whyte: General screening of the population or a more tailored population with certain indications? Because right now, most of those have focused on a limited population or are used for patients who already have a cancer, and testing that way – you think it’s going to be broader?

Dr. André: What this trial is investigating is in participants who do not have cancer, 6,000 participants ...

Dr. Whyte: Pas de tout? No cancer at all?

Dr. André: No cancer.

Dr. Whyte: No family history?

Dr. André: They can have family history, but no detectable cancer – can ctDNA analysis detect cancer? And the answer is, indeed, there is around 1% positivity, and around 40% of them, indeed, had cancer. So why is it important? Because it’s really a landmark prospective trial that is telling us that a device based on ctDNA can detect cancer at early stage. Then, how many cancers? What percentage?

Dr. Whyte: Which type of cancer?

Dr. André: And is it going to have an impact on outcome? And for all the questions, we don’t have the answer here. But the answer we have here today is that with this device, done prospectively, you can detect some cancer that would not be detectable without symptoms.

Dr. Whyte: It’s only going to get better, too.

Dr. André: Yeah. So then the next step is improving technology, integrating this technology with other ones we already have, in order to increase the percentage of patients in which we detect cancer at an earlier stage.

Dr. Whyte: What about pancreatic cancer, cancers we can’t detect through screening? People forget that most cancers cannot be detected through screening, so we need better tools. We do know that there are inherited mutations. Those really aren’t preventable in many ways; the goal is to get them early. So then we move to treatments, and you talked about precision medicine. What excites you about what’s going on these days at ESMO right now.

Dr. André: We have many trials on precision medicine. We will have two randomized trials that investigate two new targets; one is gamma secretase inhibitor. So, it’s a first-in-class, first time we even hear about this target at a clinical conference. And the second highly expected trial is a clinical trial in patients with metastatic lung cancer, KRAS mutated, testing sotorasib, which is a KRAS inhibitor, and showing the magnitude of improvement associated with sotorasib. The trial is positive, and it improved PFS [progression-free survival] in these patients. So these are two new targets that are validated at this conference.

 

 

Then, if we go on another topic of genomics, there is a question that is extremely important: Can we define patients who present an outlier sensitivity to immunotherapeutics? There will be one trial presented in the Presidential Symposium of immunotherapeutics in patients with colon cancer and microsatellite instability (MSI), showing that a few weeks of immunotherapeutics followed by surgery can cure patients. Why is it important? It’s important because we are all facing a shortage in the healthcare workforce. We have fewer nurses, fewer doctors, and we all have issues of sustainability. So, really now is the time to think about precision medicine, how precision medicine, by identifying outlier responders, can decrease the amount of resources we need to cure a patient. And this trial on immunotherapeutics, guided by genomics, is exactly this point: 8 weeks of treatment to cure a patient.

Dr. Whyte: Do you think there’s going to be a cure for cancer 10 years from now?

Dr. André: What I’m convinced of is that, in the 10 years that are coming, we are going step by step; we’re going to continue to increase the life expectancy of patients with cancer.

Dr. Whyte: And quality of life too, right?

Dr. André: Quality of life is a major issue. We had today a keynote on digital medicine and how ePRO (electronic patient-reported outcomes) can help the patient to really decrease the burden of symptoms. Quality of life is, of course, extremely important because of the very high number of patients who are cured of cancer; we need to decrease the burden of symptom in patients.

Dr. Whyte: And even though cancer rates are going down in most areas of the world, we still globally have millions of deaths from cancer every year. And sometimes people forget that, because they hear about some of the innovations. But I want to end with this: Are we investing enough in cancer care? Because let’s be honest – there are other diseases that we also need to spend time on. Cardiovascular disease is a global burden; infectious disease is a global burden. Are governments, are industries spending enough on cancer research and development?

Dr. André: Well, we can always claim for more, no? This is how everyone is trying to be, I think. But the reality is that we are living in a world where we have limited resources. I think what is more important for me is to be sure that any euro or dollar invested in cancer research is well used and generates an impact for patients. That is the most important, I think.

Dr. Whyte: And that’s why outcomes are so important in this research.

Dr. André: My conviction is that we have the tools, meaning the knowledge, the biotechnology, to really go the next step in terms of improving outcomes for patients. And for this, we now need clinical trials and translational research, but the tools, meaning basic science, basic knowledge, biotechnology – the basement for progress is here. We need now to transform this into direct impact for the patient. But I would not like to finish by saying we need more money in the field; what we need are people who can transform one euro, one dollar into concrete and measurable advances.

Dr. Whyte: We’re going to need more time on another day because I want to ask you about diversity in clinical trials, how important that is. I want to ask you about pediatric cancers; there are a whole bunch of things that I want to talk to you about. So hopefully we’ll find more time when we’re not at a big international conference such as ESMO. So, Dr Fabrice André, I want to thank you for taking time today.

Dr. André: Thank you and have a nice day.

Dr. Whyte: Stay tuned for a future discussion with Dr André on more about where we’re going in terms of cancer research and development. Thanks for watching, everyone.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

John Whyte, MD: Welcome, everyone. I’m Dr John Whyte. I’m the chief medical officer at WebMD, and I’m joined today by Fabrice André. He is the chair of the scientific committee at the European Society for Medical Oncology, where we are today in Paris, France. Bonjour, Fabrice.

So, remind our viewers: What is ESMO? What does it do? And why is it so important?

Fabrice André, MD, PhD: First ESMO, is a scientific society – a member-based organization with around 25,000 members.

Dr. Whyte: Equivalent to ASCO (American Society of Clinical Oncology) in the United States, correct?

Dr. André: It has members worldwide, from all over the world. And it aims at disseminating science, educating. The name is European, so it has some roots in Europe; but it is really a global organization for education, dissemination, and also more and more to generate frameworks for the standards of treatment and the common terminology for healthcare professionals to better care for patients.

Dr. Whyte: What are you most excited by at this conference in terms of the innovations that are being discussed?

Dr. André: Today we are at ESMO 2022 in Paris, with 28,000 people registered and the vast majority on site, and what has been the editorial line – the tagline – for the scientific committee is “understand the disease to better treat the patient.” This is extremely important; all of the educational program is built on this tagline, meaning that we need to understand what are the mechanisms of cancer progression? What are the determinants of outcomes if we want to integrate all the wealth of innovation that is coming?

So, then, what are the new things? In the Presidential Symposium, where we usually have the very new things, we will have very important presentations on the role of pollution on cancer and the biological mechanism that induces cancer. Why is it important? First, it has impact on public health. But also, it’s important because, for us, it’s raising the signal that the oncology community must start to invest in this field of prevention.

Dr. Whyte: I was at your booth, by the way, the ESMO booth here, and you have two bicycles, which impressed me. Nobody was on them, I might point out, but the focus was on prevention. But let’s also address how historically, the academic community, the scientific community hasn’t really been focused on prevention. It’s about treatment. So it’s fascinating that you’re talking about prevention, because usually we talk about precision medicine, right? We talk about checkpoint inhibitors; we talk about immunomodulators. And here you’re saying, “Hey, John, we need to understand how we prevent cancer,” which is really a misnomer in a way, because there are many different diseases. Would you agree with that?

Dr. André: I fully agree with you. But what is the premise we are trying to address here? The premise is that prevention has always been very low in the agenda of international conferences. And we think we want to give the signal that it’s really time now that clinical infrastructure, hospitals, invest in this field, create teams dedicated to prevention, new structures for prevention. Why? Because we are discovering step by step that it could be that some drugs we use for patients with cancer could also be developed in the field of prevention. And for this, we need the oncologists. So, more and more, our conviction is that it is the oncology community that will transform the field of prevention, and we need to invest now. Having said that, we have two very important abstracts on this question. The other one is about early cancer detection. But of course, we have our traditional session on immunotherapeutics, precision medicine, and all the wealth of randomized trials. And so in this field, for patients with cancer, what is the new information?

Dr. Whyte: We have this whole continuum. So you talk about prevention – how much cancer is preventable? Eighty percent? Seventy percent? What do you estimate?

Dr. André: You know, I’m also a scientist. So as a scientist, I will say that there is no limit for this question. No, the only limit is the knowledge.

Dr. Whyte: Well, there is some inherited mutation, so we do know that.

Dr. André: We can just go to the current status – what we know now – but I don’t see why we would put some limit on how much we can prevent cancer. But indeed, so far, what are the risk factors? Genetics, hereditary cancer, all habits, and we know them. It’s about tobacco, alcohol, sun, some sexual behavior, etc., that indeed account. In France, we say that around 40% of cancer could be preventable.

Dr. Whyte: More and more, we learn about the issues of gout, other inflammatory diseases; it can have an association, but then we have early screening as well. So, if we’re on this continuum, how excited are you by what’s happening with liquid biopsies, with other testing? Because if we can get a cancer instead of at 500,000 cells at the time of imaging, at 10 or 50 cells, while there are fragments, that’s revolutionary, isn’t it?

Dr. André: I fully agree with you. We will have an important trial presented during ESMO that is the first prospective trial testing the device called Galleri, a tool for early cancer detection based on ctDNA (circulating tumor DNA) analysis by methylation pattern.

Dr. Whyte: General screening of the population or a more tailored population with certain indications? Because right now, most of those have focused on a limited population or are used for patients who already have a cancer, and testing that way – you think it’s going to be broader?

Dr. André: What this trial is investigating is in participants who do not have cancer, 6,000 participants ...

Dr. Whyte: Pas de tout? No cancer at all?

Dr. André: No cancer.

Dr. Whyte: No family history?

Dr. André: They can have family history, but no detectable cancer – can ctDNA analysis detect cancer? And the answer is, indeed, there is around 1% positivity, and around 40% of them, indeed, had cancer. So why is it important? Because it’s really a landmark prospective trial that is telling us that a device based on ctDNA can detect cancer at early stage. Then, how many cancers? What percentage?

Dr. Whyte: Which type of cancer?

Dr. André: And is it going to have an impact on outcome? And for all the questions, we don’t have the answer here. But the answer we have here today is that with this device, done prospectively, you can detect some cancer that would not be detectable without symptoms.

Dr. Whyte: It’s only going to get better, too.

Dr. André: Yeah. So then the next step is improving technology, integrating this technology with other ones we already have, in order to increase the percentage of patients in which we detect cancer at an earlier stage.

Dr. Whyte: What about pancreatic cancer, cancers we can’t detect through screening? People forget that most cancers cannot be detected through screening, so we need better tools. We do know that there are inherited mutations. Those really aren’t preventable in many ways; the goal is to get them early. So then we move to treatments, and you talked about precision medicine. What excites you about what’s going on these days at ESMO right now.

Dr. André: We have many trials on precision medicine. We will have two randomized trials that investigate two new targets; one is gamma secretase inhibitor. So, it’s a first-in-class, first time we even hear about this target at a clinical conference. And the second highly expected trial is a clinical trial in patients with metastatic lung cancer, KRAS mutated, testing sotorasib, which is a KRAS inhibitor, and showing the magnitude of improvement associated with sotorasib. The trial is positive, and it improved PFS [progression-free survival] in these patients. So these are two new targets that are validated at this conference.

 

 

Then, if we go on another topic of genomics, there is a question that is extremely important: Can we define patients who present an outlier sensitivity to immunotherapeutics? There will be one trial presented in the Presidential Symposium of immunotherapeutics in patients with colon cancer and microsatellite instability (MSI), showing that a few weeks of immunotherapeutics followed by surgery can cure patients. Why is it important? It’s important because we are all facing a shortage in the healthcare workforce. We have fewer nurses, fewer doctors, and we all have issues of sustainability. So, really now is the time to think about precision medicine, how precision medicine, by identifying outlier responders, can decrease the amount of resources we need to cure a patient. And this trial on immunotherapeutics, guided by genomics, is exactly this point: 8 weeks of treatment to cure a patient.

Dr. Whyte: Do you think there’s going to be a cure for cancer 10 years from now?

Dr. André: What I’m convinced of is that, in the 10 years that are coming, we are going step by step; we’re going to continue to increase the life expectancy of patients with cancer.

Dr. Whyte: And quality of life too, right?

Dr. André: Quality of life is a major issue. We had today a keynote on digital medicine and how ePRO (electronic patient-reported outcomes) can help the patient to really decrease the burden of symptoms. Quality of life is, of course, extremely important because of the very high number of patients who are cured of cancer; we need to decrease the burden of symptom in patients.

Dr. Whyte: And even though cancer rates are going down in most areas of the world, we still globally have millions of deaths from cancer every year. And sometimes people forget that, because they hear about some of the innovations. But I want to end with this: Are we investing enough in cancer care? Because let’s be honest – there are other diseases that we also need to spend time on. Cardiovascular disease is a global burden; infectious disease is a global burden. Are governments, are industries spending enough on cancer research and development?

Dr. André: Well, we can always claim for more, no? This is how everyone is trying to be, I think. But the reality is that we are living in a world where we have limited resources. I think what is more important for me is to be sure that any euro or dollar invested in cancer research is well used and generates an impact for patients. That is the most important, I think.

Dr. Whyte: And that’s why outcomes are so important in this research.

Dr. André: My conviction is that we have the tools, meaning the knowledge, the biotechnology, to really go the next step in terms of improving outcomes for patients. And for this, we now need clinical trials and translational research, but the tools, meaning basic science, basic knowledge, biotechnology – the basement for progress is here. We need now to transform this into direct impact for the patient. But I would not like to finish by saying we need more money in the field; what we need are people who can transform one euro, one dollar into concrete and measurable advances.

Dr. Whyte: We’re going to need more time on another day because I want to ask you about diversity in clinical trials, how important that is. I want to ask you about pediatric cancers; there are a whole bunch of things that I want to talk to you about. So hopefully we’ll find more time when we’re not at a big international conference such as ESMO. So, Dr Fabrice André, I want to thank you for taking time today.

Dr. André: Thank you and have a nice day.

Dr. Whyte: Stay tuned for a future discussion with Dr André on more about where we’re going in terms of cancer research and development. Thanks for watching, everyone.

A version of this article first appeared on Medscape.com.

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Sleep apnea: Is the sleep industry part of the problem? A reporter seeks answers

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Thu, 10/13/2022 - 14:48

Editor's Note: We periodically publish patient viewpoints on specific issues of interest to our audience.

I woke up in a strange bedroom with 24 electrodes glued all over my body and a plastic mask attached to a hose covering my face.

The lab technician who watched me all night via video feed told me that I had “wicked sleep apnea” and that it was “central sleep apnea” – a type that originates in the brain and fails to tell the muscles to inhale.

As a journalist– and one terrified by the diagnosis – I set out to do my own research. After a few weeks of sleuthing and interviewing experts, I reached two important conclusions.

First, I had moderate apnea, if that, and it could be treated without the elaborate machines, mouthpieces, or other devices that specialists who had consulted on my care were talking about.

Second, the American health care system has joined with commercial partners to define a medical condition – in this case, sleep apnea – in a way that allows both parties to generate revenue from a multitude of pricey diagnostic studies, equipment sales, and questionable treatments. I was on a conveyor belt.

It all began with a desire for answers: I had been feeling drowsy during the day, and my wife told me I snored. Both can mean obstructive sleep apnea. With obstructive sleep apnea, the mouth and throat relax when a person is unconscious, sometimes blocking or narrowing the airway. That interrupts breathing, as well as sleep. Without treatment, the resulting disruption in oxygen flow might increase the risk of developing certain cardiovascular diseases.

So I contacted a sleep-treatment center, and doctors gave me an at-home test ($365). Two weeks later, they told me I had “high-moderate” sleep apnea and needed to acquire a continuous positive airway pressure (CPAP) machine, at a cost of about $600.

Though I had hoped to get the equipment and adjust the settings to see what worked best, my doctors said I had to come to the sleep lab for an overnight test ($1,900) to have them “titrate” the optimal CPAP air pressure.

“How do you treat central sleep apnea?” I worriedly asked the technician after that first overnight stay. She said something about an adaptive servo-ventilation machine ($4,000). And one pricey lab sleepover wasn’t enough, she said. I needed to come back for another.

(Most procedures and devices mentioned in this article were covered or would have been covered by insurance – in my case, Medicare, plus a supplemental plan. Unnecessary care is a big reason Americans’ insurance costs – premiums, copays, and deductibles – tend to rise year after year.)

As a journalist who spent years covering the business of health care, I found there was more motivating my expensive testing cascade than concerns about my health.

The American Academy of Sleep Medicine, a nonprofit based near Chicago, decides what is sleep apnea and how to treat it. Working with sleep societies around the world, it publishes the International Classification of Sleep Disorders, relied on by doctors everywhere to diagnose and categorize disease.

But behind that effort lie considerable conflicts of interest. Like so much of U.S. health care, sleep medicine turns out to be a thriving industry. AASM finances its operations in part with payments from CPAP machine manufacturers and other companies that stand to profit from expensive treatments and expansive definitions of apnea and other sleep disorders.

Zoll Itamar, which makes the at-home testing device I used, as well as implantable nerve-stimulation hardware for central sleep apnea, is a $60,000, “platinum” partner in AASM’s Industry Engagement Program. So is Avadel Pharmaceuticals, which is testing a drug to treat narcolepsy, characterized by intense daytime sleepiness.

Other sponsors include the maker of an anti-insomnia drug; another company with a narcolepsy drug; Fisher & Paykel Healthcare, which makes CPAP machines and masks; and Inspire Medical Systems, maker of a heavily advertised surgical implant, costing tens of thousands of dollars, to treat apnea.

Corporate sponsors for Sleep 2022, a convention AASM put on in Charlotte, N.C., with other professional societies, included many of those companies, plus Philips Respironics and ResMed, two of the biggest CPAP machine makers.

In a statement, AASM spokesperson Jennifer Gibson said a conflict-of-interest policy and a noninterference pledge from industry funders protect the integrity of the academy’s work. Industry donations account for about $170,000 of AASM’s annual revenue of about $15 million. Other revenue comes from educational materials and membership and accreditation fees.

Here’s what else I found. Almost everybody breathes irregularly sometime at night, especially during REM sleep, characterized by rapid eye movement and dreams. Blood oxygen levels also fluctuate slightly.

But recent European studies have shown that standards under the International Classification of Sleep Disorders would doom huge portions of the general population to a sleep apnea diagnosis – whether or not people had complaints of daytime tiredness or other sleep problems.

A study in Lausanne, Switzerland, showed that 50% of local men and 23% of the women 40 or older were positive for sleep apnea under such criteria.

Such rates of disease are “extraordinarily high,” “astronomical,” and “implausible,” Dirk Pevernagie, PhD, a scientist at Ghent (Belgium) University Hospital, wrote with colleagues 2 years ago in a comprehensive study in the Journal of Sleep Research.

“Right now, there is no real evidence for the criteria that have been put forward to diagnose obstructive sleep apnea and rate its severity,” he said in an interview.

Likewise, 19% of middle-aged subjects in a 2016 Icelandic study appeared to have moderate to severe “apnea” under one definition in the International Classification of Sleep Disorders even though many reported no drowsiness.

“Most of them were really surprised,” said Erna Sif Arnardóttir, who led the study and is running a large European program to refine detection and treatment of apnea.

Nevertheless, the official AASM journal recommends extremely broad screening for sleep apnea, looking for patients who have what it defines as illness. Everybody 18 and older should be screened every year for apnea if they have diabetes, obesity, untreated high blood pressure, or heart disease – even if they have never complained about sleep problems, the group says.

AASM “continually evaluates the definitions, criteria and recommendations used in the identification of sleep apnea and other sleep disorders,” Ms. Gibson said in the statement. Meanwhile, routine screening by primary care doctors “is a simple way” of gauging whether a high-risk patient may have obstructive sleep apnea, the statement said.

The U.S. Preventive Services Task Force, an authoritative body that reviews the effectiveness of preventive care, takes a conservative view, more like that of the European researchers, concluding there is “insufficient” evidence to support widespread screening among patients with no symptoms.

Many insurers refuse to pay for CPAP machines and other treatments prescribed for people at the outer edges of the AASM’s apnea definition. But AASM is pressuring them to come around.

After all my reporting, I concluded that my apnea is real, though moderate. My alarming reading in the overnight lab – diagnosed quickly as central sleep apnea – was a byproduct of the testing machinery itself. That’s a well-described phenomenon that occurs in 5% to 15% of patients.

And when I looked closely at the results of my at-home diagnostic test, I had an epiphany: My overall score was 26 breathing interruptions and blood-oxygen level declines, on average, per hour – enough to put me in the “high-moderate” category for apnea. But when I looked at the data sorted according to sleeping positions, I saw that I scored much better when I slept on my side: only 10 interruptions in an hour.

So I did a little experiment: I bought a $25 pulse oximeter with a smartphone app that records oxygen dips and breathing interruptions. When I slept on my side, there were hardly any.

Now I sleep on my side. I snore less. I wake up refreshed. I’m not daytime drowsy.

None of my specialists mentioned turning on to my side – known in medical parlance as “positional therapy” – though the intervention is recognized as effective by many researchers. Sleeping on one’s back contributes to snoring and blockages, especially as people age and the muscles in the throat become looser.

 

 

“Positional patients ... can sleep in the lateral position and sleep quite well,” said Arie Oksenberg, PhD, a sleep researcher formerly at Loewenstein Hospital in Ra’anana, Israel.

But it’s not easy to find this in the official AASM treatment guidelines, which instead go right to the money-making options like CPAP machines, surgery, central apnea, and mouth appliances.

Dealing with apnea by shifting slightly in bed gets little more than a couple of paragraphs in AASM’s guideline on “other” treatments and a little box on a long and complex decision chart.

A third or more of patients wear CPAPs only a few hours a night or stop using them. It turns out people don’t like machines in their beds.

“Positional therapy is an effective treatment option for some patients,” said Ms. Gibson. But she said there are concerns about whether patients will sleep on their sides long term and whether trying to stay in one position might cause sleep interruptions itself.

It’s true that side-sleeping doesn’t help everybody. And it often takes practice. (Some people tape a tennis ball to their pajamas to keep them off their backs.) Even conservative sleep doctors say CPAP machines are the best solution for many patients.

But there is a largely overlooked alternative.

“Are we missing a simple treatment for most adult sleep apnea patients?” was the name of a 2013 paper that Dr. Oksenberg and a colleague wrote about positional therapy.

In my case, the answer was “yes.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

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Editor's Note: We periodically publish patient viewpoints on specific issues of interest to our audience.

I woke up in a strange bedroom with 24 electrodes glued all over my body and a plastic mask attached to a hose covering my face.

The lab technician who watched me all night via video feed told me that I had “wicked sleep apnea” and that it was “central sleep apnea” – a type that originates in the brain and fails to tell the muscles to inhale.

As a journalist– and one terrified by the diagnosis – I set out to do my own research. After a few weeks of sleuthing and interviewing experts, I reached two important conclusions.

First, I had moderate apnea, if that, and it could be treated without the elaborate machines, mouthpieces, or other devices that specialists who had consulted on my care were talking about.

Second, the American health care system has joined with commercial partners to define a medical condition – in this case, sleep apnea – in a way that allows both parties to generate revenue from a multitude of pricey diagnostic studies, equipment sales, and questionable treatments. I was on a conveyor belt.

It all began with a desire for answers: I had been feeling drowsy during the day, and my wife told me I snored. Both can mean obstructive sleep apnea. With obstructive sleep apnea, the mouth and throat relax when a person is unconscious, sometimes blocking or narrowing the airway. That interrupts breathing, as well as sleep. Without treatment, the resulting disruption in oxygen flow might increase the risk of developing certain cardiovascular diseases.

So I contacted a sleep-treatment center, and doctors gave me an at-home test ($365). Two weeks later, they told me I had “high-moderate” sleep apnea and needed to acquire a continuous positive airway pressure (CPAP) machine, at a cost of about $600.

Though I had hoped to get the equipment and adjust the settings to see what worked best, my doctors said I had to come to the sleep lab for an overnight test ($1,900) to have them “titrate” the optimal CPAP air pressure.

“How do you treat central sleep apnea?” I worriedly asked the technician after that first overnight stay. She said something about an adaptive servo-ventilation machine ($4,000). And one pricey lab sleepover wasn’t enough, she said. I needed to come back for another.

(Most procedures and devices mentioned in this article were covered or would have been covered by insurance – in my case, Medicare, plus a supplemental plan. Unnecessary care is a big reason Americans’ insurance costs – premiums, copays, and deductibles – tend to rise year after year.)

As a journalist who spent years covering the business of health care, I found there was more motivating my expensive testing cascade than concerns about my health.

The American Academy of Sleep Medicine, a nonprofit based near Chicago, decides what is sleep apnea and how to treat it. Working with sleep societies around the world, it publishes the International Classification of Sleep Disorders, relied on by doctors everywhere to diagnose and categorize disease.

But behind that effort lie considerable conflicts of interest. Like so much of U.S. health care, sleep medicine turns out to be a thriving industry. AASM finances its operations in part with payments from CPAP machine manufacturers and other companies that stand to profit from expensive treatments and expansive definitions of apnea and other sleep disorders.

Zoll Itamar, which makes the at-home testing device I used, as well as implantable nerve-stimulation hardware for central sleep apnea, is a $60,000, “platinum” partner in AASM’s Industry Engagement Program. So is Avadel Pharmaceuticals, which is testing a drug to treat narcolepsy, characterized by intense daytime sleepiness.

Other sponsors include the maker of an anti-insomnia drug; another company with a narcolepsy drug; Fisher & Paykel Healthcare, which makes CPAP machines and masks; and Inspire Medical Systems, maker of a heavily advertised surgical implant, costing tens of thousands of dollars, to treat apnea.

Corporate sponsors for Sleep 2022, a convention AASM put on in Charlotte, N.C., with other professional societies, included many of those companies, plus Philips Respironics and ResMed, two of the biggest CPAP machine makers.

In a statement, AASM spokesperson Jennifer Gibson said a conflict-of-interest policy and a noninterference pledge from industry funders protect the integrity of the academy’s work. Industry donations account for about $170,000 of AASM’s annual revenue of about $15 million. Other revenue comes from educational materials and membership and accreditation fees.

Here’s what else I found. Almost everybody breathes irregularly sometime at night, especially during REM sleep, characterized by rapid eye movement and dreams. Blood oxygen levels also fluctuate slightly.

But recent European studies have shown that standards under the International Classification of Sleep Disorders would doom huge portions of the general population to a sleep apnea diagnosis – whether or not people had complaints of daytime tiredness or other sleep problems.

A study in Lausanne, Switzerland, showed that 50% of local men and 23% of the women 40 or older were positive for sleep apnea under such criteria.

Such rates of disease are “extraordinarily high,” “astronomical,” and “implausible,” Dirk Pevernagie, PhD, a scientist at Ghent (Belgium) University Hospital, wrote with colleagues 2 years ago in a comprehensive study in the Journal of Sleep Research.

“Right now, there is no real evidence for the criteria that have been put forward to diagnose obstructive sleep apnea and rate its severity,” he said in an interview.

Likewise, 19% of middle-aged subjects in a 2016 Icelandic study appeared to have moderate to severe “apnea” under one definition in the International Classification of Sleep Disorders even though many reported no drowsiness.

“Most of them were really surprised,” said Erna Sif Arnardóttir, who led the study and is running a large European program to refine detection and treatment of apnea.

Nevertheless, the official AASM journal recommends extremely broad screening for sleep apnea, looking for patients who have what it defines as illness. Everybody 18 and older should be screened every year for apnea if they have diabetes, obesity, untreated high blood pressure, or heart disease – even if they have never complained about sleep problems, the group says.

AASM “continually evaluates the definitions, criteria and recommendations used in the identification of sleep apnea and other sleep disorders,” Ms. Gibson said in the statement. Meanwhile, routine screening by primary care doctors “is a simple way” of gauging whether a high-risk patient may have obstructive sleep apnea, the statement said.

The U.S. Preventive Services Task Force, an authoritative body that reviews the effectiveness of preventive care, takes a conservative view, more like that of the European researchers, concluding there is “insufficient” evidence to support widespread screening among patients with no symptoms.

Many insurers refuse to pay for CPAP machines and other treatments prescribed for people at the outer edges of the AASM’s apnea definition. But AASM is pressuring them to come around.

After all my reporting, I concluded that my apnea is real, though moderate. My alarming reading in the overnight lab – diagnosed quickly as central sleep apnea – was a byproduct of the testing machinery itself. That’s a well-described phenomenon that occurs in 5% to 15% of patients.

And when I looked closely at the results of my at-home diagnostic test, I had an epiphany: My overall score was 26 breathing interruptions and blood-oxygen level declines, on average, per hour – enough to put me in the “high-moderate” category for apnea. But when I looked at the data sorted according to sleeping positions, I saw that I scored much better when I slept on my side: only 10 interruptions in an hour.

So I did a little experiment: I bought a $25 pulse oximeter with a smartphone app that records oxygen dips and breathing interruptions. When I slept on my side, there were hardly any.

Now I sleep on my side. I snore less. I wake up refreshed. I’m not daytime drowsy.

None of my specialists mentioned turning on to my side – known in medical parlance as “positional therapy” – though the intervention is recognized as effective by many researchers. Sleeping on one’s back contributes to snoring and blockages, especially as people age and the muscles in the throat become looser.

 

 

“Positional patients ... can sleep in the lateral position and sleep quite well,” said Arie Oksenberg, PhD, a sleep researcher formerly at Loewenstein Hospital in Ra’anana, Israel.

But it’s not easy to find this in the official AASM treatment guidelines, which instead go right to the money-making options like CPAP machines, surgery, central apnea, and mouth appliances.

Dealing with apnea by shifting slightly in bed gets little more than a couple of paragraphs in AASM’s guideline on “other” treatments and a little box on a long and complex decision chart.

A third or more of patients wear CPAPs only a few hours a night or stop using them. It turns out people don’t like machines in their beds.

“Positional therapy is an effective treatment option for some patients,” said Ms. Gibson. But she said there are concerns about whether patients will sleep on their sides long term and whether trying to stay in one position might cause sleep interruptions itself.

It’s true that side-sleeping doesn’t help everybody. And it often takes practice. (Some people tape a tennis ball to their pajamas to keep them off their backs.) Even conservative sleep doctors say CPAP machines are the best solution for many patients.

But there is a largely overlooked alternative.

“Are we missing a simple treatment for most adult sleep apnea patients?” was the name of a 2013 paper that Dr. Oksenberg and a colleague wrote about positional therapy.

In my case, the answer was “yes.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Editor's Note: We periodically publish patient viewpoints on specific issues of interest to our audience.

I woke up in a strange bedroom with 24 electrodes glued all over my body and a plastic mask attached to a hose covering my face.

The lab technician who watched me all night via video feed told me that I had “wicked sleep apnea” and that it was “central sleep apnea” – a type that originates in the brain and fails to tell the muscles to inhale.

As a journalist– and one terrified by the diagnosis – I set out to do my own research. After a few weeks of sleuthing and interviewing experts, I reached two important conclusions.

First, I had moderate apnea, if that, and it could be treated without the elaborate machines, mouthpieces, or other devices that specialists who had consulted on my care were talking about.

Second, the American health care system has joined with commercial partners to define a medical condition – in this case, sleep apnea – in a way that allows both parties to generate revenue from a multitude of pricey diagnostic studies, equipment sales, and questionable treatments. I was on a conveyor belt.

It all began with a desire for answers: I had been feeling drowsy during the day, and my wife told me I snored. Both can mean obstructive sleep apnea. With obstructive sleep apnea, the mouth and throat relax when a person is unconscious, sometimes blocking or narrowing the airway. That interrupts breathing, as well as sleep. Without treatment, the resulting disruption in oxygen flow might increase the risk of developing certain cardiovascular diseases.

So I contacted a sleep-treatment center, and doctors gave me an at-home test ($365). Two weeks later, they told me I had “high-moderate” sleep apnea and needed to acquire a continuous positive airway pressure (CPAP) machine, at a cost of about $600.

Though I had hoped to get the equipment and adjust the settings to see what worked best, my doctors said I had to come to the sleep lab for an overnight test ($1,900) to have them “titrate” the optimal CPAP air pressure.

“How do you treat central sleep apnea?” I worriedly asked the technician after that first overnight stay. She said something about an adaptive servo-ventilation machine ($4,000). And one pricey lab sleepover wasn’t enough, she said. I needed to come back for another.

(Most procedures and devices mentioned in this article were covered or would have been covered by insurance – in my case, Medicare, plus a supplemental plan. Unnecessary care is a big reason Americans’ insurance costs – premiums, copays, and deductibles – tend to rise year after year.)

As a journalist who spent years covering the business of health care, I found there was more motivating my expensive testing cascade than concerns about my health.

The American Academy of Sleep Medicine, a nonprofit based near Chicago, decides what is sleep apnea and how to treat it. Working with sleep societies around the world, it publishes the International Classification of Sleep Disorders, relied on by doctors everywhere to diagnose and categorize disease.

But behind that effort lie considerable conflicts of interest. Like so much of U.S. health care, sleep medicine turns out to be a thriving industry. AASM finances its operations in part with payments from CPAP machine manufacturers and other companies that stand to profit from expensive treatments and expansive definitions of apnea and other sleep disorders.

Zoll Itamar, which makes the at-home testing device I used, as well as implantable nerve-stimulation hardware for central sleep apnea, is a $60,000, “platinum” partner in AASM’s Industry Engagement Program. So is Avadel Pharmaceuticals, which is testing a drug to treat narcolepsy, characterized by intense daytime sleepiness.

Other sponsors include the maker of an anti-insomnia drug; another company with a narcolepsy drug; Fisher & Paykel Healthcare, which makes CPAP machines and masks; and Inspire Medical Systems, maker of a heavily advertised surgical implant, costing tens of thousands of dollars, to treat apnea.

Corporate sponsors for Sleep 2022, a convention AASM put on in Charlotte, N.C., with other professional societies, included many of those companies, plus Philips Respironics and ResMed, two of the biggest CPAP machine makers.

In a statement, AASM spokesperson Jennifer Gibson said a conflict-of-interest policy and a noninterference pledge from industry funders protect the integrity of the academy’s work. Industry donations account for about $170,000 of AASM’s annual revenue of about $15 million. Other revenue comes from educational materials and membership and accreditation fees.

Here’s what else I found. Almost everybody breathes irregularly sometime at night, especially during REM sleep, characterized by rapid eye movement and dreams. Blood oxygen levels also fluctuate slightly.

But recent European studies have shown that standards under the International Classification of Sleep Disorders would doom huge portions of the general population to a sleep apnea diagnosis – whether or not people had complaints of daytime tiredness or other sleep problems.

A study in Lausanne, Switzerland, showed that 50% of local men and 23% of the women 40 or older were positive for sleep apnea under such criteria.

Such rates of disease are “extraordinarily high,” “astronomical,” and “implausible,” Dirk Pevernagie, PhD, a scientist at Ghent (Belgium) University Hospital, wrote with colleagues 2 years ago in a comprehensive study in the Journal of Sleep Research.

“Right now, there is no real evidence for the criteria that have been put forward to diagnose obstructive sleep apnea and rate its severity,” he said in an interview.

Likewise, 19% of middle-aged subjects in a 2016 Icelandic study appeared to have moderate to severe “apnea” under one definition in the International Classification of Sleep Disorders even though many reported no drowsiness.

“Most of them were really surprised,” said Erna Sif Arnardóttir, who led the study and is running a large European program to refine detection and treatment of apnea.

Nevertheless, the official AASM journal recommends extremely broad screening for sleep apnea, looking for patients who have what it defines as illness. Everybody 18 and older should be screened every year for apnea if they have diabetes, obesity, untreated high blood pressure, or heart disease – even if they have never complained about sleep problems, the group says.

AASM “continually evaluates the definitions, criteria and recommendations used in the identification of sleep apnea and other sleep disorders,” Ms. Gibson said in the statement. Meanwhile, routine screening by primary care doctors “is a simple way” of gauging whether a high-risk patient may have obstructive sleep apnea, the statement said.

The U.S. Preventive Services Task Force, an authoritative body that reviews the effectiveness of preventive care, takes a conservative view, more like that of the European researchers, concluding there is “insufficient” evidence to support widespread screening among patients with no symptoms.

Many insurers refuse to pay for CPAP machines and other treatments prescribed for people at the outer edges of the AASM’s apnea definition. But AASM is pressuring them to come around.

After all my reporting, I concluded that my apnea is real, though moderate. My alarming reading in the overnight lab – diagnosed quickly as central sleep apnea – was a byproduct of the testing machinery itself. That’s a well-described phenomenon that occurs in 5% to 15% of patients.

And when I looked closely at the results of my at-home diagnostic test, I had an epiphany: My overall score was 26 breathing interruptions and blood-oxygen level declines, on average, per hour – enough to put me in the “high-moderate” category for apnea. But when I looked at the data sorted according to sleeping positions, I saw that I scored much better when I slept on my side: only 10 interruptions in an hour.

So I did a little experiment: I bought a $25 pulse oximeter with a smartphone app that records oxygen dips and breathing interruptions. When I slept on my side, there were hardly any.

Now I sleep on my side. I snore less. I wake up refreshed. I’m not daytime drowsy.

None of my specialists mentioned turning on to my side – known in medical parlance as “positional therapy” – though the intervention is recognized as effective by many researchers. Sleeping on one’s back contributes to snoring and blockages, especially as people age and the muscles in the throat become looser.

 

 

“Positional patients ... can sleep in the lateral position and sleep quite well,” said Arie Oksenberg, PhD, a sleep researcher formerly at Loewenstein Hospital in Ra’anana, Israel.

But it’s not easy to find this in the official AASM treatment guidelines, which instead go right to the money-making options like CPAP machines, surgery, central apnea, and mouth appliances.

Dealing with apnea by shifting slightly in bed gets little more than a couple of paragraphs in AASM’s guideline on “other” treatments and a little box on a long and complex decision chart.

A third or more of patients wear CPAPs only a few hours a night or stop using them. It turns out people don’t like machines in their beds.

“Positional therapy is an effective treatment option for some patients,” said Ms. Gibson. But she said there are concerns about whether patients will sleep on their sides long term and whether trying to stay in one position might cause sleep interruptions itself.

It’s true that side-sleeping doesn’t help everybody. And it often takes practice. (Some people tape a tennis ball to their pajamas to keep them off their backs.) Even conservative sleep doctors say CPAP machines are the best solution for many patients.

But there is a largely overlooked alternative.

“Are we missing a simple treatment for most adult sleep apnea patients?” was the name of a 2013 paper that Dr. Oksenberg and a colleague wrote about positional therapy.

In my case, the answer was “yes.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

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The hunt for N-acetylcysteine: Medicine or dietary supplement?

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Changed
Wed, 10/05/2022 - 10:59

Medicine or dietary supplement? N-acetylcysteine (NAC) is marketed as both and in 2021, the supplement abruptly became difficult to find, causing distress to people who had been using it for a variety of conditions. The story behind its disappearance is one of a cat-and-mouse chase between manufacturers, advocacy agencies, and the Food and Drug Administration.

NAC is a medication that was approved by the FDA in 1963. It has two FDA-approved uses: To prevent hepatotoxicity after overdose with acetaminophen, administered intravenously or by mouth, and as a mucolytic agent – previously available as Mucomyst, now available only as a generic – given by inhaler or nebulizer for pulmonary illnesses. Since the 1990s, NAC has been labeled by manufacturers as a dietary supplement. It is a derivative of the amino acid L-cysteine and a precursor to glutathione, an antioxidant.

Dr. Dinah Miller


NAC has caught the attention of psychiatrists because of claims that it may be useful in treating obsessive compulsive disorder (OCD), trichotillomania, and excoriation skin picking disorder (SPD), and as an adjunctive treatment for bipolar disorder. Studies have had small sample sizes, and the supplement has not been considered an “off label” use of an already available medication. People have purchased NAC from retail drug and big box stores, Amazon, and online companies. So what’s the problem?

In July 2020, the FDA issued a warning letter to Purple Biosciences LLC, because of claims on the company’s website that the product “Purple Tree,” sold by Amazon, could cure hangovers that result from alcohol intoxication. The letter discussed justification for why a hangover is a disease, and goes on to note:

Based on the product label on your website, it appears that you intend to market your Purple Tree® product, which contains N-acetyl-L-cysteine (NAC), as a dietary supplement. However, even if your product labeling did not have therapeutic claims that make your product an unapproved new drug, your product could not be a dietary supplement, because it does not meet the definition of dietary supplement ... products containing that article are outside the definition of a dietary supplement, unless before such approval that article was marketed as a dietary supplement or as a food. NAC was approved as a new drug under section 505 of the Act [21 U.S.C. § 355] on September 14, 1963.

The issue here is that because NAC was first approved as a drug in 1963, it cannot be marketed as a supplement. If it had been marketed as a supplement before it was approved as a drug by the FDA, then it could remain on the market. The fact that it had been sold as a supplement since the 1990s and could be classified as an “old dietary ingredient” according to the Dietary Supplement Health and Education Act of 1994 did not seem to matter. Following the warning letter, NAC was pulled from shelves and websites.

Citizen petitions allow people and organizations to request that the FDA change their policy. During summer 2021, there were two citizen petitions – one from the Council for Responsible Nutrition (CRN) and another from the Natural Products Association (NPA) – asking that the FDA look at policy around NAC. In response, in November 2021, the FDA put out a request for more information about how long NAC had been used and if there were safety concerns, to determine if making it a lawful supplement would be appropriate. CRN promptly released a response that they were “extremely dissatisfied” and felt this was an unnecessary tactic to delay a decision. Two members of Congress wrote letters to the FDA in support of leaving NAC as an available supplement. Congressman Jeff Duncan noted that there were over 1,170 products containing NAC.

The FDA continued to issue responses. On March 31, 2022, the agency formally denied the requests of the two citizen petitions, and 3 weeks later the Guidance for Industry: Policy Regarding N-acetyl-L-cysteine was released, saying that the FDA would “... exercise enforcement discretion with respect to the sale and distribution of certain products that contain NAC.” While NAC was still not considered a supplement, no safety issues had been identified to date. Thus, while the FDA investigation continues, the agency will essentially look the other way.

The agency will consider rulemaking to include NAC as a supplement, a process that may take years. In a notice of final guidance released in August 2022, the FDA reiterated, “unless we identify safety-related concerns during our ongoing review, FDA intends to exercise enforcement discretion until either of the following occurs: we complete notice-and-comment rulemaking to allow the use of NAC in or as a dietary supplement (should we move forward with such proceedings) or we deny the NPA citizen petition’s request for rulemaking.”

It’s a win for the consumer who wants the supplement, and a half-win for the supplement manufacturers and their advocacy organizations who would like NAC to be an official dietary supplement. But just to be clear, the issue is one of a technicality: If NAC had been marketed as a supplement before it was a drug, it would just be a dietary supplement without all the controversy and scrutiny. It was not pulled because of a clinical concern.

For now, NAC is again readily available.
 

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

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Medicine or dietary supplement? N-acetylcysteine (NAC) is marketed as both and in 2021, the supplement abruptly became difficult to find, causing distress to people who had been using it for a variety of conditions. The story behind its disappearance is one of a cat-and-mouse chase between manufacturers, advocacy agencies, and the Food and Drug Administration.

NAC is a medication that was approved by the FDA in 1963. It has two FDA-approved uses: To prevent hepatotoxicity after overdose with acetaminophen, administered intravenously or by mouth, and as a mucolytic agent – previously available as Mucomyst, now available only as a generic – given by inhaler or nebulizer for pulmonary illnesses. Since the 1990s, NAC has been labeled by manufacturers as a dietary supplement. It is a derivative of the amino acid L-cysteine and a precursor to glutathione, an antioxidant.

Dr. Dinah Miller


NAC has caught the attention of psychiatrists because of claims that it may be useful in treating obsessive compulsive disorder (OCD), trichotillomania, and excoriation skin picking disorder (SPD), and as an adjunctive treatment for bipolar disorder. Studies have had small sample sizes, and the supplement has not been considered an “off label” use of an already available medication. People have purchased NAC from retail drug and big box stores, Amazon, and online companies. So what’s the problem?

In July 2020, the FDA issued a warning letter to Purple Biosciences LLC, because of claims on the company’s website that the product “Purple Tree,” sold by Amazon, could cure hangovers that result from alcohol intoxication. The letter discussed justification for why a hangover is a disease, and goes on to note:

Based on the product label on your website, it appears that you intend to market your Purple Tree® product, which contains N-acetyl-L-cysteine (NAC), as a dietary supplement. However, even if your product labeling did not have therapeutic claims that make your product an unapproved new drug, your product could not be a dietary supplement, because it does not meet the definition of dietary supplement ... products containing that article are outside the definition of a dietary supplement, unless before such approval that article was marketed as a dietary supplement or as a food. NAC was approved as a new drug under section 505 of the Act [21 U.S.C. § 355] on September 14, 1963.

The issue here is that because NAC was first approved as a drug in 1963, it cannot be marketed as a supplement. If it had been marketed as a supplement before it was approved as a drug by the FDA, then it could remain on the market. The fact that it had been sold as a supplement since the 1990s and could be classified as an “old dietary ingredient” according to the Dietary Supplement Health and Education Act of 1994 did not seem to matter. Following the warning letter, NAC was pulled from shelves and websites.

Citizen petitions allow people and organizations to request that the FDA change their policy. During summer 2021, there were two citizen petitions – one from the Council for Responsible Nutrition (CRN) and another from the Natural Products Association (NPA) – asking that the FDA look at policy around NAC. In response, in November 2021, the FDA put out a request for more information about how long NAC had been used and if there were safety concerns, to determine if making it a lawful supplement would be appropriate. CRN promptly released a response that they were “extremely dissatisfied” and felt this was an unnecessary tactic to delay a decision. Two members of Congress wrote letters to the FDA in support of leaving NAC as an available supplement. Congressman Jeff Duncan noted that there were over 1,170 products containing NAC.

The FDA continued to issue responses. On March 31, 2022, the agency formally denied the requests of the two citizen petitions, and 3 weeks later the Guidance for Industry: Policy Regarding N-acetyl-L-cysteine was released, saying that the FDA would “... exercise enforcement discretion with respect to the sale and distribution of certain products that contain NAC.” While NAC was still not considered a supplement, no safety issues had been identified to date. Thus, while the FDA investigation continues, the agency will essentially look the other way.

The agency will consider rulemaking to include NAC as a supplement, a process that may take years. In a notice of final guidance released in August 2022, the FDA reiterated, “unless we identify safety-related concerns during our ongoing review, FDA intends to exercise enforcement discretion until either of the following occurs: we complete notice-and-comment rulemaking to allow the use of NAC in or as a dietary supplement (should we move forward with such proceedings) or we deny the NPA citizen petition’s request for rulemaking.”

It’s a win for the consumer who wants the supplement, and a half-win for the supplement manufacturers and their advocacy organizations who would like NAC to be an official dietary supplement. But just to be clear, the issue is one of a technicality: If NAC had been marketed as a supplement before it was a drug, it would just be a dietary supplement without all the controversy and scrutiny. It was not pulled because of a clinical concern.

For now, NAC is again readily available.
 

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

Medicine or dietary supplement? N-acetylcysteine (NAC) is marketed as both and in 2021, the supplement abruptly became difficult to find, causing distress to people who had been using it for a variety of conditions. The story behind its disappearance is one of a cat-and-mouse chase between manufacturers, advocacy agencies, and the Food and Drug Administration.

NAC is a medication that was approved by the FDA in 1963. It has two FDA-approved uses: To prevent hepatotoxicity after overdose with acetaminophen, administered intravenously or by mouth, and as a mucolytic agent – previously available as Mucomyst, now available only as a generic – given by inhaler or nebulizer for pulmonary illnesses. Since the 1990s, NAC has been labeled by manufacturers as a dietary supplement. It is a derivative of the amino acid L-cysteine and a precursor to glutathione, an antioxidant.

Dr. Dinah Miller


NAC has caught the attention of psychiatrists because of claims that it may be useful in treating obsessive compulsive disorder (OCD), trichotillomania, and excoriation skin picking disorder (SPD), and as an adjunctive treatment for bipolar disorder. Studies have had small sample sizes, and the supplement has not been considered an “off label” use of an already available medication. People have purchased NAC from retail drug and big box stores, Amazon, and online companies. So what’s the problem?

In July 2020, the FDA issued a warning letter to Purple Biosciences LLC, because of claims on the company’s website that the product “Purple Tree,” sold by Amazon, could cure hangovers that result from alcohol intoxication. The letter discussed justification for why a hangover is a disease, and goes on to note:

Based on the product label on your website, it appears that you intend to market your Purple Tree® product, which contains N-acetyl-L-cysteine (NAC), as a dietary supplement. However, even if your product labeling did not have therapeutic claims that make your product an unapproved new drug, your product could not be a dietary supplement, because it does not meet the definition of dietary supplement ... products containing that article are outside the definition of a dietary supplement, unless before such approval that article was marketed as a dietary supplement or as a food. NAC was approved as a new drug under section 505 of the Act [21 U.S.C. § 355] on September 14, 1963.

The issue here is that because NAC was first approved as a drug in 1963, it cannot be marketed as a supplement. If it had been marketed as a supplement before it was approved as a drug by the FDA, then it could remain on the market. The fact that it had been sold as a supplement since the 1990s and could be classified as an “old dietary ingredient” according to the Dietary Supplement Health and Education Act of 1994 did not seem to matter. Following the warning letter, NAC was pulled from shelves and websites.

Citizen petitions allow people and organizations to request that the FDA change their policy. During summer 2021, there were two citizen petitions – one from the Council for Responsible Nutrition (CRN) and another from the Natural Products Association (NPA) – asking that the FDA look at policy around NAC. In response, in November 2021, the FDA put out a request for more information about how long NAC had been used and if there were safety concerns, to determine if making it a lawful supplement would be appropriate. CRN promptly released a response that they were “extremely dissatisfied” and felt this was an unnecessary tactic to delay a decision. Two members of Congress wrote letters to the FDA in support of leaving NAC as an available supplement. Congressman Jeff Duncan noted that there were over 1,170 products containing NAC.

The FDA continued to issue responses. On March 31, 2022, the agency formally denied the requests of the two citizen petitions, and 3 weeks later the Guidance for Industry: Policy Regarding N-acetyl-L-cysteine was released, saying that the FDA would “... exercise enforcement discretion with respect to the sale and distribution of certain products that contain NAC.” While NAC was still not considered a supplement, no safety issues had been identified to date. Thus, while the FDA investigation continues, the agency will essentially look the other way.

The agency will consider rulemaking to include NAC as a supplement, a process that may take years. In a notice of final guidance released in August 2022, the FDA reiterated, “unless we identify safety-related concerns during our ongoing review, FDA intends to exercise enforcement discretion until either of the following occurs: we complete notice-and-comment rulemaking to allow the use of NAC in or as a dietary supplement (should we move forward with such proceedings) or we deny the NPA citizen petition’s request for rulemaking.”

It’s a win for the consumer who wants the supplement, and a half-win for the supplement manufacturers and their advocacy organizations who would like NAC to be an official dietary supplement. But just to be clear, the issue is one of a technicality: If NAC had been marketed as a supplement before it was a drug, it would just be a dietary supplement without all the controversy and scrutiny. It was not pulled because of a clinical concern.

For now, NAC is again readily available.
 

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

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Had my patient come in today, we may have had other options

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Changed
Tue, 10/04/2022 - 15:47

Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.

Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.

NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.

Dr. Joan H. Schiller

In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.

Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
 

Companion tests

Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

 

 

Other approvals

T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).

T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.

For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
 

Trastuzumab emtansine vs. trastuzumab deruxtecan

Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.

ILDs

In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).

Chemotherapy-like adverse effects

Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

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Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.

Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.

NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.

Dr. Joan H. Schiller

In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.

Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
 

Companion tests

Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

 

 

Other approvals

T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).

T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.

For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
 

Trastuzumab emtansine vs. trastuzumab deruxtecan

Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.

ILDs

In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).

Chemotherapy-like adverse effects

Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.

Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.

NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.

Dr. Joan H. Schiller

In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.

Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
 

Companion tests

Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

 

 

Other approvals

T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).

T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.

For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
 

Trastuzumab emtansine vs. trastuzumab deruxtecan

Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.

ILDs

In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).

Chemotherapy-like adverse effects

Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

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