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If we care about cancer patients, we must care about climate change
Because we care about our patients, we need to get involved in the climate change movement. If we want to help prevent cancer and deliver the best possible care to our patients, we need to stop burning fossil fuels. As addressed in an earlier version of this column, burning fossil fuels results in the release of particulate matter and particles measuring 2.5 micrometers in diameter (PM2.5), are classified as group 1 carcinogens by the International Association of Research and Cancer.
Fossil fuels also release greenhouse gases (carbon dioxide, methane, nitrous oxide, and fluorinated gases) which trap solar radiation that would otherwise have been reflected back into space after hitting the earth’s surface. Instead, it is redirected back to earth as infrared radiation warming the planet by 1.1° C since preindustrial times.
Climate change has a number of consequences, including more extreme weather events, rising sea levels, warming seas, environmental degradation, and affects water and food quality, supply, and production. A global increase of 1.5° C above the preindustrial average risks catastrophic harm to health that will be impossible to reverse, prompting the editors of over 260 health journals to call for emergency action to limit global temperature increases, restore biodiversity, and protect health.
In October, the 2022 version of the Lancet Countdown on health and climate change was issued and the findings are not good. “After 30 years of UNFCCC negotiations, the Lancet Countdown indicators show that countries and companies continue to make choices that threaten the health and survival of people in every part of the world. As countries devise ways to recover from the coexisting crises, the evidence is unequivocal. At this critical juncture, an immediate, health-centered response can still secure a future in which world populations can not only survive, but thrive,” the authors wrote. Governments and companies continue to prioritize fossil fuels over people’s health.
Among the key findings from the report, Marina Romanello, PhD, of the Institute for Global Health at University College London, and her colleagues, call for “A health-centered response to the coexisting climate, energy, and cost-of-living crises provides an opportunity to deliver a healthy, low-carbon future. The associated reduction in the burden of disease will in turn reduce the strain on overwhelmed health care providers, and enable better care.”
The authors also state that “Well-prepared health systems are essential to protect populations from the health impacts of climate change. However, global health systems have been drastically weakened by the effects of the COVID-19 pandemic, and the funds available for climate action decreased in 239 (30%) of 798 cities, with health systems increasingly being affected by extreme weather events and supply chain disruptions.”
And, the authors are concerned that health systems have left themselves vulnerable to climate change–related health hazards because they have not adapted their operations for climate-related changes. “Only 48 of 95 countries have assessed their climate change adaptation needs and only 63% of countries reported high to very high implementation status for health emergency management in 2021. Increasing adaptation to climate change has the potential to simultaneously improve the capacity of health systems to manage both future infectious disease outbreaks and other health emergencies.”
There is roughly a 50% chance that the 1.5° C threshold proposed in the Paris Agreement will be exceeded within 5 years. The carbon intensity of the global energy system has been reduced by less than 1% from 1992 levels, when the United Nations Framework Convention on Climate Change was adopted. At our current pace, global emissions could be 13.7% above 2010 levels by 2030 and fully decarbonizing the energy system would take 150 years. Clearly, we are nowhere near meeting the goals of the Paris Agreement signed in 2015 by 192 countries and the European Union. Participants pledged to decrease their carbon footprint by 50% by 2030, and net zero by the end of the century.
The effect of increasing greenhouse gases in our atmosphere will have a massive impact on the prevention and care of cancer patients. Air pollution is responsible for about 14% of lung cancer deaths throughout the world. Rising temperatures lead to extreme weather events which disrupts infrastructure and the ability to access health care, leading to delays in treatment, increased morbidity, and death. Screening rates for cancer go down, which leads to more patients presenting with advanced cancer in the future.
As oncologists who care deeply about their patients, we need to get actively involved. It is our responsibility to our current and future patients to do whatever we can to prevent cancer and reduce its complications.
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.
Because we care about our patients, we need to get involved in the climate change movement. If we want to help prevent cancer and deliver the best possible care to our patients, we need to stop burning fossil fuels. As addressed in an earlier version of this column, burning fossil fuels results in the release of particulate matter and particles measuring 2.5 micrometers in diameter (PM2.5), are classified as group 1 carcinogens by the International Association of Research and Cancer.
Fossil fuels also release greenhouse gases (carbon dioxide, methane, nitrous oxide, and fluorinated gases) which trap solar radiation that would otherwise have been reflected back into space after hitting the earth’s surface. Instead, it is redirected back to earth as infrared radiation warming the planet by 1.1° C since preindustrial times.
Climate change has a number of consequences, including more extreme weather events, rising sea levels, warming seas, environmental degradation, and affects water and food quality, supply, and production. A global increase of 1.5° C above the preindustrial average risks catastrophic harm to health that will be impossible to reverse, prompting the editors of over 260 health journals to call for emergency action to limit global temperature increases, restore biodiversity, and protect health.
In October, the 2022 version of the Lancet Countdown on health and climate change was issued and the findings are not good. “After 30 years of UNFCCC negotiations, the Lancet Countdown indicators show that countries and companies continue to make choices that threaten the health and survival of people in every part of the world. As countries devise ways to recover from the coexisting crises, the evidence is unequivocal. At this critical juncture, an immediate, health-centered response can still secure a future in which world populations can not only survive, but thrive,” the authors wrote. Governments and companies continue to prioritize fossil fuels over people’s health.
Among the key findings from the report, Marina Romanello, PhD, of the Institute for Global Health at University College London, and her colleagues, call for “A health-centered response to the coexisting climate, energy, and cost-of-living crises provides an opportunity to deliver a healthy, low-carbon future. The associated reduction in the burden of disease will in turn reduce the strain on overwhelmed health care providers, and enable better care.”
The authors also state that “Well-prepared health systems are essential to protect populations from the health impacts of climate change. However, global health systems have been drastically weakened by the effects of the COVID-19 pandemic, and the funds available for climate action decreased in 239 (30%) of 798 cities, with health systems increasingly being affected by extreme weather events and supply chain disruptions.”
And, the authors are concerned that health systems have left themselves vulnerable to climate change–related health hazards because they have not adapted their operations for climate-related changes. “Only 48 of 95 countries have assessed their climate change adaptation needs and only 63% of countries reported high to very high implementation status for health emergency management in 2021. Increasing adaptation to climate change has the potential to simultaneously improve the capacity of health systems to manage both future infectious disease outbreaks and other health emergencies.”
There is roughly a 50% chance that the 1.5° C threshold proposed in the Paris Agreement will be exceeded within 5 years. The carbon intensity of the global energy system has been reduced by less than 1% from 1992 levels, when the United Nations Framework Convention on Climate Change was adopted. At our current pace, global emissions could be 13.7% above 2010 levels by 2030 and fully decarbonizing the energy system would take 150 years. Clearly, we are nowhere near meeting the goals of the Paris Agreement signed in 2015 by 192 countries and the European Union. Participants pledged to decrease their carbon footprint by 50% by 2030, and net zero by the end of the century.
The effect of increasing greenhouse gases in our atmosphere will have a massive impact on the prevention and care of cancer patients. Air pollution is responsible for about 14% of lung cancer deaths throughout the world. Rising temperatures lead to extreme weather events which disrupts infrastructure and the ability to access health care, leading to delays in treatment, increased morbidity, and death. Screening rates for cancer go down, which leads to more patients presenting with advanced cancer in the future.
As oncologists who care deeply about their patients, we need to get actively involved. It is our responsibility to our current and future patients to do whatever we can to prevent cancer and reduce its complications.
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.
Because we care about our patients, we need to get involved in the climate change movement. If we want to help prevent cancer and deliver the best possible care to our patients, we need to stop burning fossil fuels. As addressed in an earlier version of this column, burning fossil fuels results in the release of particulate matter and particles measuring 2.5 micrometers in diameter (PM2.5), are classified as group 1 carcinogens by the International Association of Research and Cancer.
Fossil fuels also release greenhouse gases (carbon dioxide, methane, nitrous oxide, and fluorinated gases) which trap solar radiation that would otherwise have been reflected back into space after hitting the earth’s surface. Instead, it is redirected back to earth as infrared radiation warming the planet by 1.1° C since preindustrial times.
Climate change has a number of consequences, including more extreme weather events, rising sea levels, warming seas, environmental degradation, and affects water and food quality, supply, and production. A global increase of 1.5° C above the preindustrial average risks catastrophic harm to health that will be impossible to reverse, prompting the editors of over 260 health journals to call for emergency action to limit global temperature increases, restore biodiversity, and protect health.
In October, the 2022 version of the Lancet Countdown on health and climate change was issued and the findings are not good. “After 30 years of UNFCCC negotiations, the Lancet Countdown indicators show that countries and companies continue to make choices that threaten the health and survival of people in every part of the world. As countries devise ways to recover from the coexisting crises, the evidence is unequivocal. At this critical juncture, an immediate, health-centered response can still secure a future in which world populations can not only survive, but thrive,” the authors wrote. Governments and companies continue to prioritize fossil fuels over people’s health.
Among the key findings from the report, Marina Romanello, PhD, of the Institute for Global Health at University College London, and her colleagues, call for “A health-centered response to the coexisting climate, energy, and cost-of-living crises provides an opportunity to deliver a healthy, low-carbon future. The associated reduction in the burden of disease will in turn reduce the strain on overwhelmed health care providers, and enable better care.”
The authors also state that “Well-prepared health systems are essential to protect populations from the health impacts of climate change. However, global health systems have been drastically weakened by the effects of the COVID-19 pandemic, and the funds available for climate action decreased in 239 (30%) of 798 cities, with health systems increasingly being affected by extreme weather events and supply chain disruptions.”
And, the authors are concerned that health systems have left themselves vulnerable to climate change–related health hazards because they have not adapted their operations for climate-related changes. “Only 48 of 95 countries have assessed their climate change adaptation needs and only 63% of countries reported high to very high implementation status for health emergency management in 2021. Increasing adaptation to climate change has the potential to simultaneously improve the capacity of health systems to manage both future infectious disease outbreaks and other health emergencies.”
There is roughly a 50% chance that the 1.5° C threshold proposed in the Paris Agreement will be exceeded within 5 years. The carbon intensity of the global energy system has been reduced by less than 1% from 1992 levels, when the United Nations Framework Convention on Climate Change was adopted. At our current pace, global emissions could be 13.7% above 2010 levels by 2030 and fully decarbonizing the energy system would take 150 years. Clearly, we are nowhere near meeting the goals of the Paris Agreement signed in 2015 by 192 countries and the European Union. Participants pledged to decrease their carbon footprint by 50% by 2030, and net zero by the end of the century.
The effect of increasing greenhouse gases in our atmosphere will have a massive impact on the prevention and care of cancer patients. Air pollution is responsible for about 14% of lung cancer deaths throughout the world. Rising temperatures lead to extreme weather events which disrupts infrastructure and the ability to access health care, leading to delays in treatment, increased morbidity, and death. Screening rates for cancer go down, which leads to more patients presenting with advanced cancer in the future.
As oncologists who care deeply about their patients, we need to get actively involved. It is our responsibility to our current and future patients to do whatever we can to prevent cancer and reduce its complications.
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.
Severe health diagnoses drive suicide risk
Individuals diagnosed with a severe physical health condition were significantly more likely to commit suicide at 6 months and at 1 year later, based on data from more than 47 million individuals in a national database.
Previous smaller studies have shown a link between increased risk for suicide and a range of health conditions including cancer, coronary heart disease, neurologic conditions, diabetes, and osteoporosis, Vahé Nafilyan, PhD, of the Office for National Statistics, Newport, England, and colleagues wrote.
However, large-scale population-level studies of the association between specific diagnoses and suicide are lacking, they said.
In a study published in The Lancet Regional Health–Europe, the researchers reviewed a dataset that combined the 2011 Census, death registration records, and the Hospital Episode Statistics. The study population included 47,354,696 individuals aged 6 years and older living in England in 2017. The mean age of the study population was 39.6 years, and 52% were female. The researchers examined deaths that occurred between Jan. 1, 2017, and Dec. 31, 2021.
The health conditions included in the analysis were low-survival cancers, chronic ischemic heart disease, chronic obstructive pulmonary disease, and degenerative neurological disease.
The diagnosis of any of these conditions significantly increased the risk for suicide compared with controls. The highest risk appeared within 6 months of a diagnosis or first treatment, but the increased risk persisted at 1 year.
The suicide rate among low-survival cancer patients was 16.6 per 100,000 patients, compared with 5.7 per 100,000 controls; at 1 year, these rates were 21.6 and 9.5 per 100,000 patients and controls, respectively.
For COPD patients, the suicide rate at 6 months after diagnosis was 13.7 per 100,000 patients versus 5.6 per 100,000 matched controls; the suicide rates at 1 year were 22.4 per 100,000 patients and 10.6 per 100,000 matched controls.
The suicide rate at 6 months for individuals diagnosed with chronic ischemic heart disease was 11.0 per 100,000 patients and 4.2 per 100,000 matched controls; at 1 year, the suicide rates were 16.1 per 100,000 patients and 8.8 per 100,000 matched controls.
The 1-year suicide rate was especially high among patients with degenerative neurological conditions (114.5 per 100,000 patients); however, the estimate was considered imprecise because of the rarity of these diseases and subsequent low number of suicides, the researchers noted.
The results support data from previous studies showing links between increased risk of suicide and severe physical conditions, the researchers wrote. Patterns of suicide were similar between men and women and after adjusting for sociodemographic factors.
The findings were limited by the inability to fully control for a history of depression or self-harm, and by the imprecise estimates given the rare occurrence of suicide overall, the researchers noted. Other limitations included the late registration of deaths from external causes and the focus only on suicides that occurred in England and Wales, meaning that individuals who traveled abroad for assisted suicide were not captured in the dataset.
“Further research is needed to understand the mechanisms driving the elevated risk of suicide and help provide the best support to these patients,” the researchers concluded.
However, the current results enhance the literature with a large, population-based review of the elevated suicide risk among individuals newly diagnosed with severe health conditions, and reflect the need for better support for these patients to help with coping, they said.
The study was funded by the Office for National Statistics. The researchers reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Individuals diagnosed with a severe physical health condition were significantly more likely to commit suicide at 6 months and at 1 year later, based on data from more than 47 million individuals in a national database.
Previous smaller studies have shown a link between increased risk for suicide and a range of health conditions including cancer, coronary heart disease, neurologic conditions, diabetes, and osteoporosis, Vahé Nafilyan, PhD, of the Office for National Statistics, Newport, England, and colleagues wrote.
However, large-scale population-level studies of the association between specific diagnoses and suicide are lacking, they said.
In a study published in The Lancet Regional Health–Europe, the researchers reviewed a dataset that combined the 2011 Census, death registration records, and the Hospital Episode Statistics. The study population included 47,354,696 individuals aged 6 years and older living in England in 2017. The mean age of the study population was 39.6 years, and 52% were female. The researchers examined deaths that occurred between Jan. 1, 2017, and Dec. 31, 2021.
The health conditions included in the analysis were low-survival cancers, chronic ischemic heart disease, chronic obstructive pulmonary disease, and degenerative neurological disease.
The diagnosis of any of these conditions significantly increased the risk for suicide compared with controls. The highest risk appeared within 6 months of a diagnosis or first treatment, but the increased risk persisted at 1 year.
The suicide rate among low-survival cancer patients was 16.6 per 100,000 patients, compared with 5.7 per 100,000 controls; at 1 year, these rates were 21.6 and 9.5 per 100,000 patients and controls, respectively.
For COPD patients, the suicide rate at 6 months after diagnosis was 13.7 per 100,000 patients versus 5.6 per 100,000 matched controls; the suicide rates at 1 year were 22.4 per 100,000 patients and 10.6 per 100,000 matched controls.
The suicide rate at 6 months for individuals diagnosed with chronic ischemic heart disease was 11.0 per 100,000 patients and 4.2 per 100,000 matched controls; at 1 year, the suicide rates were 16.1 per 100,000 patients and 8.8 per 100,000 matched controls.
The 1-year suicide rate was especially high among patients with degenerative neurological conditions (114.5 per 100,000 patients); however, the estimate was considered imprecise because of the rarity of these diseases and subsequent low number of suicides, the researchers noted.
The results support data from previous studies showing links between increased risk of suicide and severe physical conditions, the researchers wrote. Patterns of suicide were similar between men and women and after adjusting for sociodemographic factors.
The findings were limited by the inability to fully control for a history of depression or self-harm, and by the imprecise estimates given the rare occurrence of suicide overall, the researchers noted. Other limitations included the late registration of deaths from external causes and the focus only on suicides that occurred in England and Wales, meaning that individuals who traveled abroad for assisted suicide were not captured in the dataset.
“Further research is needed to understand the mechanisms driving the elevated risk of suicide and help provide the best support to these patients,” the researchers concluded.
However, the current results enhance the literature with a large, population-based review of the elevated suicide risk among individuals newly diagnosed with severe health conditions, and reflect the need for better support for these patients to help with coping, they said.
The study was funded by the Office for National Statistics. The researchers reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Individuals diagnosed with a severe physical health condition were significantly more likely to commit suicide at 6 months and at 1 year later, based on data from more than 47 million individuals in a national database.
Previous smaller studies have shown a link between increased risk for suicide and a range of health conditions including cancer, coronary heart disease, neurologic conditions, diabetes, and osteoporosis, Vahé Nafilyan, PhD, of the Office for National Statistics, Newport, England, and colleagues wrote.
However, large-scale population-level studies of the association between specific diagnoses and suicide are lacking, they said.
In a study published in The Lancet Regional Health–Europe, the researchers reviewed a dataset that combined the 2011 Census, death registration records, and the Hospital Episode Statistics. The study population included 47,354,696 individuals aged 6 years and older living in England in 2017. The mean age of the study population was 39.6 years, and 52% were female. The researchers examined deaths that occurred between Jan. 1, 2017, and Dec. 31, 2021.
The health conditions included in the analysis were low-survival cancers, chronic ischemic heart disease, chronic obstructive pulmonary disease, and degenerative neurological disease.
The diagnosis of any of these conditions significantly increased the risk for suicide compared with controls. The highest risk appeared within 6 months of a diagnosis or first treatment, but the increased risk persisted at 1 year.
The suicide rate among low-survival cancer patients was 16.6 per 100,000 patients, compared with 5.7 per 100,000 controls; at 1 year, these rates were 21.6 and 9.5 per 100,000 patients and controls, respectively.
For COPD patients, the suicide rate at 6 months after diagnosis was 13.7 per 100,000 patients versus 5.6 per 100,000 matched controls; the suicide rates at 1 year were 22.4 per 100,000 patients and 10.6 per 100,000 matched controls.
The suicide rate at 6 months for individuals diagnosed with chronic ischemic heart disease was 11.0 per 100,000 patients and 4.2 per 100,000 matched controls; at 1 year, the suicide rates were 16.1 per 100,000 patients and 8.8 per 100,000 matched controls.
The 1-year suicide rate was especially high among patients with degenerative neurological conditions (114.5 per 100,000 patients); however, the estimate was considered imprecise because of the rarity of these diseases and subsequent low number of suicides, the researchers noted.
The results support data from previous studies showing links between increased risk of suicide and severe physical conditions, the researchers wrote. Patterns of suicide were similar between men and women and after adjusting for sociodemographic factors.
The findings were limited by the inability to fully control for a history of depression or self-harm, and by the imprecise estimates given the rare occurrence of suicide overall, the researchers noted. Other limitations included the late registration of deaths from external causes and the focus only on suicides that occurred in England and Wales, meaning that individuals who traveled abroad for assisted suicide were not captured in the dataset.
“Further research is needed to understand the mechanisms driving the elevated risk of suicide and help provide the best support to these patients,” the researchers concluded.
However, the current results enhance the literature with a large, population-based review of the elevated suicide risk among individuals newly diagnosed with severe health conditions, and reflect the need for better support for these patients to help with coping, they said.
The study was funded by the Office for National Statistics. The researchers reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM THE LANCET REGIONAL HEALTH–EUROPE
The longevity gene: Healthy mutant reverses heart aging
Everybody wants a younger heart
As more people live well past 90, scientists have been taking a closer look at how they’ve been doing it. Mostly it boiled down to genetics. You either had it or you didn’t. Well, a recent study suggests that doesn’t have to be true anymore, at least for the heart.
Scientists from the United Kingdom and Italy found an antiaging gene in some centenarians that has shown possible antiaging effects in mice and in human heart cells. A single administration of the mutant antiaging gene, they found, stopped heart function decay in middle-aged mice and even reversed the biological clock by the human equivalent of 10 years in elderly mice.
When the researchers applied the antiaging gene to samples of human heart cells from elderly people with heart problems, the cells “resumed functioning properly, proving to be more efficient in building new blood vessels,” they said in a written statement. It all kind of sounds like something out of Dr. Frankenstein’s lab.
I want to believe … in better sleep
The “X-Files” theme song plays. Mulder and Scully are sitting in a diner, breakfast laid out around them. The diner is quiet, with only a few people inside.
Mulder: I’m telling you, Scully, there’s something spooky going on here.
Scully: You mean other than the fact that this town in Georgia looks suspiciously like Vancouver?
Mulder: Not one person we spoke to yesterday has gotten a full night’s sleep since the UFO sighting last month. I’m telling you, they’re here, they’re experimenting.
Scully: Do you really want me to do this to you again?
Mulder: Do what again?
Scully: There’s nothing going on here that can’t be explained by the current research. Why, in January 2023 a study was published revealing a link between poor sleep and belief in paranormal phenomena like UFOS, demons, or ghosts. Which probably explains why you’re on your third cup of coffee for the morning.
Mulder: Scully, you’ve literally been abducted by aliens. Do we have to play this game every time?
Scully: Look, it’s simple. In a sample of nearly 9,000 people, nearly two-thirds of those who reported experiencing sleep paralysis or exploding head syndrome reported believing in UFOs and aliens walking amongst humanity, despite making up just 3% of the overall sample.
Furthermore, about 60% of those reporting sleep paralysis also reported believing near-death experiences prove the soul lingers on after death, and those with stronger insomnia symptoms were more likely to believe in the devil.
Mulder: Aha!
Scully: Aha what?
Mulder: You’re a devout Christian. You believe in the devil and the soul.
Scully: Yes, but I don’t let it interfere with a good night’s sleep, Mulder. These people saw something strange, convinced themselves it was a UFO, and now they can’t sleep. It’s a vicious cycle. The study authors even said that people experiencing strange nighttime phenomena could interpret this as evidence of aliens or other paranormal beings, thus making them even more susceptible to further sleep disruption and deepening beliefs. Look who I’m talking to.
Mulder: Always with the facts, eh?
Scully: I am a doctor, after all. And if you want more research into how paranormal belief and poor sleep quality are linked, I’d be happy to dig out the literature, because the truth is out there, Mulder.
Mulder: I hate you sometimes.
It’s ChatGPT’s world. We’re just living in it
Have you heard about ChatGPT? The artificial intelligence chatbot was just launched in November and it’s already more important to the Internet than either Vladimir Putin or “Rick and Morty.”
What’s that? You’re wondering why you should care? Well, excuuuuuse us, but we thought you might want to know that ChatGPT is in the process of taking over the world. Let’s take a quick look at what it’s been up to.
“ChatGPT bot passes law school exam”
“ChatGPT passes MBA exam given by a Wharton professor”
“A freelance writer says ChatGPT wrote a $600 article in just 30 seconds”
And here’s one that might be of interest to those of the health care persuasion: “ChatGPT can pass part of the U.S. Medical Licensing Exam.” See? It’s coming for you, too.
The artificial intelligence known as ChatGPT “performed at >50% accuracy across [the three USMLE] examinations, exceeding 60% in most analyses,” a group of researchers wrote on the preprint server medRxiv, noting that 60% is usually the pass threshold for humans taking the exam in any given year.
ChatGPT was not given any special medical training before the exam, but the investigators pointed out that another AI, PubMedGPT, which is trained exclusively on biomedical domain literature, was only 50.8% accurate on the USMLE. Its reliance on “ongoing academic discourse that tends to be inconclusive, contradictory, or highly conservative or noncommittal in its language” was its undoing, the team suggested.
To top it off, ChatGPT is listed as one of the authors at the top of the medRxiv report, with an acknowledgment at the end saying that “ChatGPT contributed to the writing of several sections of this manuscript.”
We’ve said it before, and no doubt we’ll say it again: We’re doomed.
Everybody wants a younger heart
As more people live well past 90, scientists have been taking a closer look at how they’ve been doing it. Mostly it boiled down to genetics. You either had it or you didn’t. Well, a recent study suggests that doesn’t have to be true anymore, at least for the heart.
Scientists from the United Kingdom and Italy found an antiaging gene in some centenarians that has shown possible antiaging effects in mice and in human heart cells. A single administration of the mutant antiaging gene, they found, stopped heart function decay in middle-aged mice and even reversed the biological clock by the human equivalent of 10 years in elderly mice.
When the researchers applied the antiaging gene to samples of human heart cells from elderly people with heart problems, the cells “resumed functioning properly, proving to be more efficient in building new blood vessels,” they said in a written statement. It all kind of sounds like something out of Dr. Frankenstein’s lab.
I want to believe … in better sleep
The “X-Files” theme song plays. Mulder and Scully are sitting in a diner, breakfast laid out around them. The diner is quiet, with only a few people inside.
Mulder: I’m telling you, Scully, there’s something spooky going on here.
Scully: You mean other than the fact that this town in Georgia looks suspiciously like Vancouver?
Mulder: Not one person we spoke to yesterday has gotten a full night’s sleep since the UFO sighting last month. I’m telling you, they’re here, they’re experimenting.
Scully: Do you really want me to do this to you again?
Mulder: Do what again?
Scully: There’s nothing going on here that can’t be explained by the current research. Why, in January 2023 a study was published revealing a link between poor sleep and belief in paranormal phenomena like UFOS, demons, or ghosts. Which probably explains why you’re on your third cup of coffee for the morning.
Mulder: Scully, you’ve literally been abducted by aliens. Do we have to play this game every time?
Scully: Look, it’s simple. In a sample of nearly 9,000 people, nearly two-thirds of those who reported experiencing sleep paralysis or exploding head syndrome reported believing in UFOs and aliens walking amongst humanity, despite making up just 3% of the overall sample.
Furthermore, about 60% of those reporting sleep paralysis also reported believing near-death experiences prove the soul lingers on after death, and those with stronger insomnia symptoms were more likely to believe in the devil.
Mulder: Aha!
Scully: Aha what?
Mulder: You’re a devout Christian. You believe in the devil and the soul.
Scully: Yes, but I don’t let it interfere with a good night’s sleep, Mulder. These people saw something strange, convinced themselves it was a UFO, and now they can’t sleep. It’s a vicious cycle. The study authors even said that people experiencing strange nighttime phenomena could interpret this as evidence of aliens or other paranormal beings, thus making them even more susceptible to further sleep disruption and deepening beliefs. Look who I’m talking to.
Mulder: Always with the facts, eh?
Scully: I am a doctor, after all. And if you want more research into how paranormal belief and poor sleep quality are linked, I’d be happy to dig out the literature, because the truth is out there, Mulder.
Mulder: I hate you sometimes.
It’s ChatGPT’s world. We’re just living in it
Have you heard about ChatGPT? The artificial intelligence chatbot was just launched in November and it’s already more important to the Internet than either Vladimir Putin or “Rick and Morty.”
What’s that? You’re wondering why you should care? Well, excuuuuuse us, but we thought you might want to know that ChatGPT is in the process of taking over the world. Let’s take a quick look at what it’s been up to.
“ChatGPT bot passes law school exam”
“ChatGPT passes MBA exam given by a Wharton professor”
“A freelance writer says ChatGPT wrote a $600 article in just 30 seconds”
And here’s one that might be of interest to those of the health care persuasion: “ChatGPT can pass part of the U.S. Medical Licensing Exam.” See? It’s coming for you, too.
The artificial intelligence known as ChatGPT “performed at >50% accuracy across [the three USMLE] examinations, exceeding 60% in most analyses,” a group of researchers wrote on the preprint server medRxiv, noting that 60% is usually the pass threshold for humans taking the exam in any given year.
ChatGPT was not given any special medical training before the exam, but the investigators pointed out that another AI, PubMedGPT, which is trained exclusively on biomedical domain literature, was only 50.8% accurate on the USMLE. Its reliance on “ongoing academic discourse that tends to be inconclusive, contradictory, or highly conservative or noncommittal in its language” was its undoing, the team suggested.
To top it off, ChatGPT is listed as one of the authors at the top of the medRxiv report, with an acknowledgment at the end saying that “ChatGPT contributed to the writing of several sections of this manuscript.”
We’ve said it before, and no doubt we’ll say it again: We’re doomed.
Everybody wants a younger heart
As more people live well past 90, scientists have been taking a closer look at how they’ve been doing it. Mostly it boiled down to genetics. You either had it or you didn’t. Well, a recent study suggests that doesn’t have to be true anymore, at least for the heart.
Scientists from the United Kingdom and Italy found an antiaging gene in some centenarians that has shown possible antiaging effects in mice and in human heart cells. A single administration of the mutant antiaging gene, they found, stopped heart function decay in middle-aged mice and even reversed the biological clock by the human equivalent of 10 years in elderly mice.
When the researchers applied the antiaging gene to samples of human heart cells from elderly people with heart problems, the cells “resumed functioning properly, proving to be more efficient in building new blood vessels,” they said in a written statement. It all kind of sounds like something out of Dr. Frankenstein’s lab.
I want to believe … in better sleep
The “X-Files” theme song plays. Mulder and Scully are sitting in a diner, breakfast laid out around them. The diner is quiet, with only a few people inside.
Mulder: I’m telling you, Scully, there’s something spooky going on here.
Scully: You mean other than the fact that this town in Georgia looks suspiciously like Vancouver?
Mulder: Not one person we spoke to yesterday has gotten a full night’s sleep since the UFO sighting last month. I’m telling you, they’re here, they’re experimenting.
Scully: Do you really want me to do this to you again?
Mulder: Do what again?
Scully: There’s nothing going on here that can’t be explained by the current research. Why, in January 2023 a study was published revealing a link between poor sleep and belief in paranormal phenomena like UFOS, demons, or ghosts. Which probably explains why you’re on your third cup of coffee for the morning.
Mulder: Scully, you’ve literally been abducted by aliens. Do we have to play this game every time?
Scully: Look, it’s simple. In a sample of nearly 9,000 people, nearly two-thirds of those who reported experiencing sleep paralysis or exploding head syndrome reported believing in UFOs and aliens walking amongst humanity, despite making up just 3% of the overall sample.
Furthermore, about 60% of those reporting sleep paralysis also reported believing near-death experiences prove the soul lingers on after death, and those with stronger insomnia symptoms were more likely to believe in the devil.
Mulder: Aha!
Scully: Aha what?
Mulder: You’re a devout Christian. You believe in the devil and the soul.
Scully: Yes, but I don’t let it interfere with a good night’s sleep, Mulder. These people saw something strange, convinced themselves it was a UFO, and now they can’t sleep. It’s a vicious cycle. The study authors even said that people experiencing strange nighttime phenomena could interpret this as evidence of aliens or other paranormal beings, thus making them even more susceptible to further sleep disruption and deepening beliefs. Look who I’m talking to.
Mulder: Always with the facts, eh?
Scully: I am a doctor, after all. And if you want more research into how paranormal belief and poor sleep quality are linked, I’d be happy to dig out the literature, because the truth is out there, Mulder.
Mulder: I hate you sometimes.
It’s ChatGPT’s world. We’re just living in it
Have you heard about ChatGPT? The artificial intelligence chatbot was just launched in November and it’s already more important to the Internet than either Vladimir Putin or “Rick and Morty.”
What’s that? You’re wondering why you should care? Well, excuuuuuse us, but we thought you might want to know that ChatGPT is in the process of taking over the world. Let’s take a quick look at what it’s been up to.
“ChatGPT bot passes law school exam”
“ChatGPT passes MBA exam given by a Wharton professor”
“A freelance writer says ChatGPT wrote a $600 article in just 30 seconds”
And here’s one that might be of interest to those of the health care persuasion: “ChatGPT can pass part of the U.S. Medical Licensing Exam.” See? It’s coming for you, too.
The artificial intelligence known as ChatGPT “performed at >50% accuracy across [the three USMLE] examinations, exceeding 60% in most analyses,” a group of researchers wrote on the preprint server medRxiv, noting that 60% is usually the pass threshold for humans taking the exam in any given year.
ChatGPT was not given any special medical training before the exam, but the investigators pointed out that another AI, PubMedGPT, which is trained exclusively on biomedical domain literature, was only 50.8% accurate on the USMLE. Its reliance on “ongoing academic discourse that tends to be inconclusive, contradictory, or highly conservative or noncommittal in its language” was its undoing, the team suggested.
To top it off, ChatGPT is listed as one of the authors at the top of the medRxiv report, with an acknowledgment at the end saying that “ChatGPT contributed to the writing of several sections of this manuscript.”
We’ve said it before, and no doubt we’ll say it again: We’re doomed.
Patients with COPD at higher risk of death 1 year after surgery
Patients with chronic obstructive pulmonary disease (COPD) are more likely to die within a year of undergoing elective surgery and to incur higher health care costs than are similar patients without COPD, data suggest.
An analysis of close to a million patient records found that, after adjustment for sociodemographic factors, procedure type, and comorbidities, patients with COPD were 26% more likely to die in the year after surgery than were those without COPD. Moreover, COPD was associated with a 4.6% increase in health care costs.
Previous studies have evaluated outcomes for the first 30 days after surgery. Those data “may not adequately capture the overall burden of surgery and how long it may take patients to recover,” study author Ashwin Sankar, MD, a clinician-investigator at St. Michael’s Hospital and assistant professor of anesthesia at the University of Toronto, told this news organization.
“We found that COPD often coexists with other conditions, like diabetes, coronary artery disease, and frailty,” Dr. Sankar added.
The study was published online in the Canadian Medical Association Journal.
Additional recovery support
The authors analyzed data from 932,616 patients who underwent intermediate-risk to high-risk elective noncardiac surgeries from 2005 to 2019 in Ontario. Procedures included carotid endarterectomy, open or endovascular abdominal aortic aneurysm repair, peripheral arterial bypass, total hip replacement, total knee replacement, shoulder surgery, large-bowel surgery, partial liver resection, pancreaticoduodenectomy, gastrectomy, esophagectomy, nephrectomy, cystectomy, prostatectomy, and hysterectomy.
The researchers quantified the associations of COPD with survival and costs. Their analyses included partial adjustment for sociodemographic factors and procedure type and full adjustment, which included comorbidities.
The primary outcome was all-cause death in the year after surgery; the secondary outcome was total health care costs in that year.
The mean age of the population was 65 years, and 60% of patients were women. A total of 170,482 (18%) patients had COPD. Compared with those without COPD, the patients with COPD were older and were more likely to be male, to be in a lower income quintile, to be residents of long-term care facilities, and to have been admitted to the hospital before surgery. They were also more likely to have comorbidities, including coronary artery disease, heart failure, and lung cancer.
A larger proportion of patients with COPD had frailty and medium to high comorbidity. They also more frequently underwent orthopedic, open upper abdominal, and vascular surgery.
During the year after surgery, 52,021 (5.6%) patients died, including 18,007 (10.6%) with COPD and 34,014 (4.5%) without. Those with COPD were more likely to die within 30 days of surgery (3.4% vs 1.2%).
For patients with COPD, the partially adjusted hazard ratio (HR) was 1.61 for risk of death; the fully adjusted HR was 1.26. COPD also was associated with a partially adjusted relative increase of 13.1% in health care costs and an increase of 4.6% with full adjustment.
Frailty, cancer, and procedure type were factors that modified the association between COPD and outcomes. “Procedures such as open aortic and upper abdominal surgery are associated with higher postoperative risks irrespective of COPD status, whereas others, such as orthopedic and lower abdominal surgery, may be of significantly greater risk for patients with COPD,” the authors wrote. “Our results suggest that perioperative management of patients with COPD requires careful consideration of the multiple domains that contribute to their elevated perioperative risk.
“Our finding that patients with COPD are at risk beyond 30 days after surgery suggests that it may be worthwhile to additionally support these patients’ recovery well beyond the first month after the procedure,” said Dr. Sankar.
Shared decision-making
Commenting on the study, William Whalen, MD, a pulmonary critical care specialist at Weill Cornell Medicine in New York, said, “I echo the authors’ sentiments that these findings highlight how chronically ill COPD patients are, which may be playing a role in the elevated mortality seen in this study.”
One caveat is in regard to the interpretation of the interaction effects of the study, he said. “Clinicians are unlikely to send patients who are frail or have multiple comorbidities to overly complex surgeries. Therefore, these effects may be misestimated due to selection bias.”
Two questions remain after reading the study, he added. “The first is how the degree of obstruction (i.e., the severity of COPD) impacts long-term mortality. Previous observational studies in nonsurgical COPD patients have shown increased mortality as the severity of obstruction increases. The second is how much of the long-term mortality observed in this study is related to respiratory disease from COPD. Patients with COPD are complex, and many die from nonrespiratory-related causes.”
Dr. Whalen suggests that discussion be held with the surgical team about the long-term morbidity and mortality with and without surgical intervention. Such a discussion could inform a shared decision-making process with the patient.
“Some procedures may be necessary to reduce immediate mortality, such as aortic aneurysmal repair, so [the risk of] longer-term mortality may be more acceptable in this setting,” he said. “Less straightforward are procedures that may improve quality of life. Would a patient accept an increased long-term mortality [risk] if that meant living without orthopedic-related pain?”
The study was funded by the Government of Ontario. Dr. Sankar and Dr. Whalen have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with chronic obstructive pulmonary disease (COPD) are more likely to die within a year of undergoing elective surgery and to incur higher health care costs than are similar patients without COPD, data suggest.
An analysis of close to a million patient records found that, after adjustment for sociodemographic factors, procedure type, and comorbidities, patients with COPD were 26% more likely to die in the year after surgery than were those without COPD. Moreover, COPD was associated with a 4.6% increase in health care costs.
Previous studies have evaluated outcomes for the first 30 days after surgery. Those data “may not adequately capture the overall burden of surgery and how long it may take patients to recover,” study author Ashwin Sankar, MD, a clinician-investigator at St. Michael’s Hospital and assistant professor of anesthesia at the University of Toronto, told this news organization.
“We found that COPD often coexists with other conditions, like diabetes, coronary artery disease, and frailty,” Dr. Sankar added.
The study was published online in the Canadian Medical Association Journal.
Additional recovery support
The authors analyzed data from 932,616 patients who underwent intermediate-risk to high-risk elective noncardiac surgeries from 2005 to 2019 in Ontario. Procedures included carotid endarterectomy, open or endovascular abdominal aortic aneurysm repair, peripheral arterial bypass, total hip replacement, total knee replacement, shoulder surgery, large-bowel surgery, partial liver resection, pancreaticoduodenectomy, gastrectomy, esophagectomy, nephrectomy, cystectomy, prostatectomy, and hysterectomy.
The researchers quantified the associations of COPD with survival and costs. Their analyses included partial adjustment for sociodemographic factors and procedure type and full adjustment, which included comorbidities.
The primary outcome was all-cause death in the year after surgery; the secondary outcome was total health care costs in that year.
The mean age of the population was 65 years, and 60% of patients were women. A total of 170,482 (18%) patients had COPD. Compared with those without COPD, the patients with COPD were older and were more likely to be male, to be in a lower income quintile, to be residents of long-term care facilities, and to have been admitted to the hospital before surgery. They were also more likely to have comorbidities, including coronary artery disease, heart failure, and lung cancer.
A larger proportion of patients with COPD had frailty and medium to high comorbidity. They also more frequently underwent orthopedic, open upper abdominal, and vascular surgery.
During the year after surgery, 52,021 (5.6%) patients died, including 18,007 (10.6%) with COPD and 34,014 (4.5%) without. Those with COPD were more likely to die within 30 days of surgery (3.4% vs 1.2%).
For patients with COPD, the partially adjusted hazard ratio (HR) was 1.61 for risk of death; the fully adjusted HR was 1.26. COPD also was associated with a partially adjusted relative increase of 13.1% in health care costs and an increase of 4.6% with full adjustment.
Frailty, cancer, and procedure type were factors that modified the association between COPD and outcomes. “Procedures such as open aortic and upper abdominal surgery are associated with higher postoperative risks irrespective of COPD status, whereas others, such as orthopedic and lower abdominal surgery, may be of significantly greater risk for patients with COPD,” the authors wrote. “Our results suggest that perioperative management of patients with COPD requires careful consideration of the multiple domains that contribute to their elevated perioperative risk.
“Our finding that patients with COPD are at risk beyond 30 days after surgery suggests that it may be worthwhile to additionally support these patients’ recovery well beyond the first month after the procedure,” said Dr. Sankar.
Shared decision-making
Commenting on the study, William Whalen, MD, a pulmonary critical care specialist at Weill Cornell Medicine in New York, said, “I echo the authors’ sentiments that these findings highlight how chronically ill COPD patients are, which may be playing a role in the elevated mortality seen in this study.”
One caveat is in regard to the interpretation of the interaction effects of the study, he said. “Clinicians are unlikely to send patients who are frail or have multiple comorbidities to overly complex surgeries. Therefore, these effects may be misestimated due to selection bias.”
Two questions remain after reading the study, he added. “The first is how the degree of obstruction (i.e., the severity of COPD) impacts long-term mortality. Previous observational studies in nonsurgical COPD patients have shown increased mortality as the severity of obstruction increases. The second is how much of the long-term mortality observed in this study is related to respiratory disease from COPD. Patients with COPD are complex, and many die from nonrespiratory-related causes.”
Dr. Whalen suggests that discussion be held with the surgical team about the long-term morbidity and mortality with and without surgical intervention. Such a discussion could inform a shared decision-making process with the patient.
“Some procedures may be necessary to reduce immediate mortality, such as aortic aneurysmal repair, so [the risk of] longer-term mortality may be more acceptable in this setting,” he said. “Less straightforward are procedures that may improve quality of life. Would a patient accept an increased long-term mortality [risk] if that meant living without orthopedic-related pain?”
The study was funded by the Government of Ontario. Dr. Sankar and Dr. Whalen have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with chronic obstructive pulmonary disease (COPD) are more likely to die within a year of undergoing elective surgery and to incur higher health care costs than are similar patients without COPD, data suggest.
An analysis of close to a million patient records found that, after adjustment for sociodemographic factors, procedure type, and comorbidities, patients with COPD were 26% more likely to die in the year after surgery than were those without COPD. Moreover, COPD was associated with a 4.6% increase in health care costs.
Previous studies have evaluated outcomes for the first 30 days after surgery. Those data “may not adequately capture the overall burden of surgery and how long it may take patients to recover,” study author Ashwin Sankar, MD, a clinician-investigator at St. Michael’s Hospital and assistant professor of anesthesia at the University of Toronto, told this news organization.
“We found that COPD often coexists with other conditions, like diabetes, coronary artery disease, and frailty,” Dr. Sankar added.
The study was published online in the Canadian Medical Association Journal.
Additional recovery support
The authors analyzed data from 932,616 patients who underwent intermediate-risk to high-risk elective noncardiac surgeries from 2005 to 2019 in Ontario. Procedures included carotid endarterectomy, open or endovascular abdominal aortic aneurysm repair, peripheral arterial bypass, total hip replacement, total knee replacement, shoulder surgery, large-bowel surgery, partial liver resection, pancreaticoduodenectomy, gastrectomy, esophagectomy, nephrectomy, cystectomy, prostatectomy, and hysterectomy.
The researchers quantified the associations of COPD with survival and costs. Their analyses included partial adjustment for sociodemographic factors and procedure type and full adjustment, which included comorbidities.
The primary outcome was all-cause death in the year after surgery; the secondary outcome was total health care costs in that year.
The mean age of the population was 65 years, and 60% of patients were women. A total of 170,482 (18%) patients had COPD. Compared with those without COPD, the patients with COPD were older and were more likely to be male, to be in a lower income quintile, to be residents of long-term care facilities, and to have been admitted to the hospital before surgery. They were also more likely to have comorbidities, including coronary artery disease, heart failure, and lung cancer.
A larger proportion of patients with COPD had frailty and medium to high comorbidity. They also more frequently underwent orthopedic, open upper abdominal, and vascular surgery.
During the year after surgery, 52,021 (5.6%) patients died, including 18,007 (10.6%) with COPD and 34,014 (4.5%) without. Those with COPD were more likely to die within 30 days of surgery (3.4% vs 1.2%).
For patients with COPD, the partially adjusted hazard ratio (HR) was 1.61 for risk of death; the fully adjusted HR was 1.26. COPD also was associated with a partially adjusted relative increase of 13.1% in health care costs and an increase of 4.6% with full adjustment.
Frailty, cancer, and procedure type were factors that modified the association between COPD and outcomes. “Procedures such as open aortic and upper abdominal surgery are associated with higher postoperative risks irrespective of COPD status, whereas others, such as orthopedic and lower abdominal surgery, may be of significantly greater risk for patients with COPD,” the authors wrote. “Our results suggest that perioperative management of patients with COPD requires careful consideration of the multiple domains that contribute to their elevated perioperative risk.
“Our finding that patients with COPD are at risk beyond 30 days after surgery suggests that it may be worthwhile to additionally support these patients’ recovery well beyond the first month after the procedure,” said Dr. Sankar.
Shared decision-making
Commenting on the study, William Whalen, MD, a pulmonary critical care specialist at Weill Cornell Medicine in New York, said, “I echo the authors’ sentiments that these findings highlight how chronically ill COPD patients are, which may be playing a role in the elevated mortality seen in this study.”
One caveat is in regard to the interpretation of the interaction effects of the study, he said. “Clinicians are unlikely to send patients who are frail or have multiple comorbidities to overly complex surgeries. Therefore, these effects may be misestimated due to selection bias.”
Two questions remain after reading the study, he added. “The first is how the degree of obstruction (i.e., the severity of COPD) impacts long-term mortality. Previous observational studies in nonsurgical COPD patients have shown increased mortality as the severity of obstruction increases. The second is how much of the long-term mortality observed in this study is related to respiratory disease from COPD. Patients with COPD are complex, and many die from nonrespiratory-related causes.”
Dr. Whalen suggests that discussion be held with the surgical team about the long-term morbidity and mortality with and without surgical intervention. Such a discussion could inform a shared decision-making process with the patient.
“Some procedures may be necessary to reduce immediate mortality, such as aortic aneurysmal repair, so [the risk of] longer-term mortality may be more acceptable in this setting,” he said. “Less straightforward are procedures that may improve quality of life. Would a patient accept an increased long-term mortality [risk] if that meant living without orthopedic-related pain?”
The study was funded by the Government of Ontario. Dr. Sankar and Dr. Whalen have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Canadian guidance recommends reducing alcohol consumption
“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).
Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:
- Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
- Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
- Three to six drinks raise the risk of developing breast, colon, and other cancers.
- Seven or more increase the risk of heart disease or stroke.
- Each additional drink “radically increases” the risk of these health consequences.
“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”
Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”
“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
Continuum of risk
The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.
That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.
Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).
Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:
- Low for individuals who consume two standard drinks or fewer per week
- Moderate for those who consume from three to six standard drinks per week
- Increasingly high for those who consume seven standard drinks or more per week
The guidance makes the following observations:
- Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
- When pregnant or trying to get pregnant, no amount of alcohol is safe.
- When breastfeeding, not drinking is safest.
- Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
- Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
- Young people should delay alcohol use for as long as possible.
- Individuals should not start to use alcohol or increase their alcohol use for health benefits.
- Any reduction in alcohol use is beneficial.
Other national guidelines
“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”
“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.
“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”
Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”
Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.
Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”
A version of this article originally appeared on Medscape.com.
“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).
Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:
- Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
- Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
- Three to six drinks raise the risk of developing breast, colon, and other cancers.
- Seven or more increase the risk of heart disease or stroke.
- Each additional drink “radically increases” the risk of these health consequences.
“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”
Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”
“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
Continuum of risk
The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.
That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.
Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).
Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:
- Low for individuals who consume two standard drinks or fewer per week
- Moderate for those who consume from three to six standard drinks per week
- Increasingly high for those who consume seven standard drinks or more per week
The guidance makes the following observations:
- Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
- When pregnant or trying to get pregnant, no amount of alcohol is safe.
- When breastfeeding, not drinking is safest.
- Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
- Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
- Young people should delay alcohol use for as long as possible.
- Individuals should not start to use alcohol or increase their alcohol use for health benefits.
- Any reduction in alcohol use is beneficial.
Other national guidelines
“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”
“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.
“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”
Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”
Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.
Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”
A version of this article originally appeared on Medscape.com.
“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).
Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:
- Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
- Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
- Three to six drinks raise the risk of developing breast, colon, and other cancers.
- Seven or more increase the risk of heart disease or stroke.
- Each additional drink “radically increases” the risk of these health consequences.
“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”
Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”
“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
Continuum of risk
The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.
That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.
Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).
Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:
- Low for individuals who consume two standard drinks or fewer per week
- Moderate for those who consume from three to six standard drinks per week
- Increasingly high for those who consume seven standard drinks or more per week
The guidance makes the following observations:
- Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
- When pregnant or trying to get pregnant, no amount of alcohol is safe.
- When breastfeeding, not drinking is safest.
- Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
- Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
- Young people should delay alcohol use for as long as possible.
- Individuals should not start to use alcohol or increase their alcohol use for health benefits.
- Any reduction in alcohol use is beneficial.
Other national guidelines
“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”
“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.
“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”
Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”
Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.
Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”
A version of this article originally appeared on Medscape.com.
Tips for getting involved with industry
Introduction
The professional activity of physicians has traditionally consisted of patient care, teaching/education, and research in varying proportions. These aims, especially education and research, have traditionally been achieved in academic health settings. However, involvement with industry can afford all physicians an opportunity to increase patient referrals, gain exposure to colleagues through a variety of educational opportunities, and participate in meaningful research projects they could not initiate independently.
How to initiate relationships with industry
Here are several ways to initiate a collaboration with industry. A few of the most common ways are to become a site investigator of a multicenter device or pharmaceutical trial, participate as a member of a speaker’s bureau, or obtain training on a new technology and subsequently incorporate it into your clinical practice. To find out what trials are enrolling and looking for additional sites or new studies that are being planned, I would suggest contacting the company’s local representative and have them put you in touch the appropriate personnel in the clinical trials division. For individuals who become involved in trials, this can be a great way to improve your understanding of how to design and conduct clinical trials as well as gain exposure to colleagues with similar clinical and research interests. Some of my closest long-term collaborators and friends have been individuals who I initially met as part of industry trials at investigator meetings. Another approach is to participate in a speaker’s bureau, which can be an excellent way to improve one’s presentation skills as well as gain knowledge with respect to a specific disease state. It is also a great way to network, meet colleagues, and develop a local and regional reputation as a content expert on a specific topic. Methods to find out about such opportunities include touring the exhibit halls during educational meetings and reading scientific journals to identify new products that are launching. I have found these sorts of opportunities can significantly increase topic-based referrals. Finally, obtaining training on a new diagnostic or therapeutic technology (usually through an industry-sponsored course) can allow individuals an opportunity to offer a unique or distinctive service to their community. In addition, as further clinical expertise is gained, the relationship can be expanded to offer local, regional, or even national training courses to colleagues via either on-site or virtual courses. Similarly, opportunities to speak about or demonstrate the technology/technique at educational courses may also follow.
Navigating and expanding the relationship
Once an individual establishes a relationship with a company or has established a reputation as a key opinion leader, additional opportunities for engagement may become available. These include serving as a consultant, becoming a member of an advisory board, participating or directing educational courses for trainees/practitioners, or serving as the principal investigator of a future clinical trial. Serving as a consultant can be quite rewarding as it can highlight clinical needs, identify where product improvement can be achieved, and focus where research and development funds should be directed. Serving on the advisory board can afford an even higher level of influence where corporate strategy can be influenced. Such input is particularly impactful with smaller companies looking to enter a new field or expand a limited market share. There are also a variety of educational opportunities offered by industry including local, regional, and national courses that focus on utilizing a new technology or education concerning a specific disease state. These courses can be held locally at the physician’s clinical site or off site to attract the desired target audience. Finally, being involved in research studies, especially early-stage projects, can be critical as many small companies have limited capital, and it is essential for them to design studies with appropriate endpoints that will ideally achieve both regulatory approval as well as payor coverage. Of note, in addition to relationships directly involving industry, the American Gastroenterological Association Center for GI Innovation and Technology (CGIT) also offers the opportunity to be part of key opinion leader meetings arranged and organized by the AGA. This may allow for some individuals to participate who may be restricted from direct relationships with industry partners. The industry services offered by the CGIT also include clinical trial design and registry management services.
Entrepreneurship/intellectual property
A less commonly explored opportunity with industry involves the development of one’s own intellectual property. Some of the most impactful technologies in my advanced endoscopy clinical practice have been developed from the ideas of gastroenterology colleagues that have been successfully commercialized. These include radiofrequency ablation technology to treat Barrett’s esophagus and the development of lumen-apposing stents. There are several options for physicians with an idea for an innovation. These can include working with a university technology transfer department if they are in an academic setting, creation of their own company, or collaborating with industry to develop the device through a licensing/royalty agreement. The AGA CGIT offers extensive resources to physicians with new ideas on how to secure their intellectual property as well as to evaluate the feasibility of the aforementioned options to choose which may be most appropriate for them.
Important caveats
It is important that physicians with industry relations be aware of their local institutional policies. Some institutions may prohibit such activities while others may limit the types of relationships or the amount of income that can be received. It is the physician’s responsibility to be aware of their institution’s guidelines prior to formalizing industry agreements. If intellectual property is involved, it is essential to know the specific rules regarding physician remuneration, especially pertaining to royalty or equity agreements. Furthermore, with regard to presentations and publications, it is required to acknowledge industry relations and potential conflicts of interest. Failure to do so may adversely affect an individual’s reputation as well as lead to additional consequences such as the potential for retraction of publications or restrictions regarding future educational speaking opportunities. In addition, key opinion leaders often consult for several companies that may be in competition with each other. Therefore, it is essential that there is no disclosure of confidential proprietary information among companies. Finally, the financial incentives resulting from industry collaboration should never influence physician judgment when interpreting or speaking about data regarding product efficacy or safety.
Conclusions
In summary, there are numerous opportunities for physicians to collaborate with industry. These relationships can be very rewarding and can serve to expedite the introduction of new diagnostic or treatment modalities and provide the opportunity to network and interact with colleagues as well as to participate in important research that improves clinical practice. The nature of these relationships should always be transparent, and it is the physician’s responsibility to ensure that the types of relationships that are engaged in are permitted by their employer. Over the course of my career, I have participated in nearly all forms of these relationships and have seen that participation lead to important publications, changes in corporate strategy, the fostering of acquisitions, and the rapid development and utilization of new endoscopic technologies. It is my personal belief than industry relationships can improve professional satisfaction, enhance one’s brand, and most importantly, expedite clinical innovation to improve patient care.
Dr. Muthusamy is professor of clinical medicine at the University of California, Los Angeles, and medical director of endoscopy, UCLA Health System. He disclosed ties with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.
Introduction
The professional activity of physicians has traditionally consisted of patient care, teaching/education, and research in varying proportions. These aims, especially education and research, have traditionally been achieved in academic health settings. However, involvement with industry can afford all physicians an opportunity to increase patient referrals, gain exposure to colleagues through a variety of educational opportunities, and participate in meaningful research projects they could not initiate independently.
How to initiate relationships with industry
Here are several ways to initiate a collaboration with industry. A few of the most common ways are to become a site investigator of a multicenter device or pharmaceutical trial, participate as a member of a speaker’s bureau, or obtain training on a new technology and subsequently incorporate it into your clinical practice. To find out what trials are enrolling and looking for additional sites or new studies that are being planned, I would suggest contacting the company’s local representative and have them put you in touch the appropriate personnel in the clinical trials division. For individuals who become involved in trials, this can be a great way to improve your understanding of how to design and conduct clinical trials as well as gain exposure to colleagues with similar clinical and research interests. Some of my closest long-term collaborators and friends have been individuals who I initially met as part of industry trials at investigator meetings. Another approach is to participate in a speaker’s bureau, which can be an excellent way to improve one’s presentation skills as well as gain knowledge with respect to a specific disease state. It is also a great way to network, meet colleagues, and develop a local and regional reputation as a content expert on a specific topic. Methods to find out about such opportunities include touring the exhibit halls during educational meetings and reading scientific journals to identify new products that are launching. I have found these sorts of opportunities can significantly increase topic-based referrals. Finally, obtaining training on a new diagnostic or therapeutic technology (usually through an industry-sponsored course) can allow individuals an opportunity to offer a unique or distinctive service to their community. In addition, as further clinical expertise is gained, the relationship can be expanded to offer local, regional, or even national training courses to colleagues via either on-site or virtual courses. Similarly, opportunities to speak about or demonstrate the technology/technique at educational courses may also follow.
Navigating and expanding the relationship
Once an individual establishes a relationship with a company or has established a reputation as a key opinion leader, additional opportunities for engagement may become available. These include serving as a consultant, becoming a member of an advisory board, participating or directing educational courses for trainees/practitioners, or serving as the principal investigator of a future clinical trial. Serving as a consultant can be quite rewarding as it can highlight clinical needs, identify where product improvement can be achieved, and focus where research and development funds should be directed. Serving on the advisory board can afford an even higher level of influence where corporate strategy can be influenced. Such input is particularly impactful with smaller companies looking to enter a new field or expand a limited market share. There are also a variety of educational opportunities offered by industry including local, regional, and national courses that focus on utilizing a new technology or education concerning a specific disease state. These courses can be held locally at the physician’s clinical site or off site to attract the desired target audience. Finally, being involved in research studies, especially early-stage projects, can be critical as many small companies have limited capital, and it is essential for them to design studies with appropriate endpoints that will ideally achieve both regulatory approval as well as payor coverage. Of note, in addition to relationships directly involving industry, the American Gastroenterological Association Center for GI Innovation and Technology (CGIT) also offers the opportunity to be part of key opinion leader meetings arranged and organized by the AGA. This may allow for some individuals to participate who may be restricted from direct relationships with industry partners. The industry services offered by the CGIT also include clinical trial design and registry management services.
Entrepreneurship/intellectual property
A less commonly explored opportunity with industry involves the development of one’s own intellectual property. Some of the most impactful technologies in my advanced endoscopy clinical practice have been developed from the ideas of gastroenterology colleagues that have been successfully commercialized. These include radiofrequency ablation technology to treat Barrett’s esophagus and the development of lumen-apposing stents. There are several options for physicians with an idea for an innovation. These can include working with a university technology transfer department if they are in an academic setting, creation of their own company, or collaborating with industry to develop the device through a licensing/royalty agreement. The AGA CGIT offers extensive resources to physicians with new ideas on how to secure their intellectual property as well as to evaluate the feasibility of the aforementioned options to choose which may be most appropriate for them.
Important caveats
It is important that physicians with industry relations be aware of their local institutional policies. Some institutions may prohibit such activities while others may limit the types of relationships or the amount of income that can be received. It is the physician’s responsibility to be aware of their institution’s guidelines prior to formalizing industry agreements. If intellectual property is involved, it is essential to know the specific rules regarding physician remuneration, especially pertaining to royalty or equity agreements. Furthermore, with regard to presentations and publications, it is required to acknowledge industry relations and potential conflicts of interest. Failure to do so may adversely affect an individual’s reputation as well as lead to additional consequences such as the potential for retraction of publications or restrictions regarding future educational speaking opportunities. In addition, key opinion leaders often consult for several companies that may be in competition with each other. Therefore, it is essential that there is no disclosure of confidential proprietary information among companies. Finally, the financial incentives resulting from industry collaboration should never influence physician judgment when interpreting or speaking about data regarding product efficacy or safety.
Conclusions
In summary, there are numerous opportunities for physicians to collaborate with industry. These relationships can be very rewarding and can serve to expedite the introduction of new diagnostic or treatment modalities and provide the opportunity to network and interact with colleagues as well as to participate in important research that improves clinical practice. The nature of these relationships should always be transparent, and it is the physician’s responsibility to ensure that the types of relationships that are engaged in are permitted by their employer. Over the course of my career, I have participated in nearly all forms of these relationships and have seen that participation lead to important publications, changes in corporate strategy, the fostering of acquisitions, and the rapid development and utilization of new endoscopic technologies. It is my personal belief than industry relationships can improve professional satisfaction, enhance one’s brand, and most importantly, expedite clinical innovation to improve patient care.
Dr. Muthusamy is professor of clinical medicine at the University of California, Los Angeles, and medical director of endoscopy, UCLA Health System. He disclosed ties with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.
Introduction
The professional activity of physicians has traditionally consisted of patient care, teaching/education, and research in varying proportions. These aims, especially education and research, have traditionally been achieved in academic health settings. However, involvement with industry can afford all physicians an opportunity to increase patient referrals, gain exposure to colleagues through a variety of educational opportunities, and participate in meaningful research projects they could not initiate independently.
How to initiate relationships with industry
Here are several ways to initiate a collaboration with industry. A few of the most common ways are to become a site investigator of a multicenter device or pharmaceutical trial, participate as a member of a speaker’s bureau, or obtain training on a new technology and subsequently incorporate it into your clinical practice. To find out what trials are enrolling and looking for additional sites or new studies that are being planned, I would suggest contacting the company’s local representative and have them put you in touch the appropriate personnel in the clinical trials division. For individuals who become involved in trials, this can be a great way to improve your understanding of how to design and conduct clinical trials as well as gain exposure to colleagues with similar clinical and research interests. Some of my closest long-term collaborators and friends have been individuals who I initially met as part of industry trials at investigator meetings. Another approach is to participate in a speaker’s bureau, which can be an excellent way to improve one’s presentation skills as well as gain knowledge with respect to a specific disease state. It is also a great way to network, meet colleagues, and develop a local and regional reputation as a content expert on a specific topic. Methods to find out about such opportunities include touring the exhibit halls during educational meetings and reading scientific journals to identify new products that are launching. I have found these sorts of opportunities can significantly increase topic-based referrals. Finally, obtaining training on a new diagnostic or therapeutic technology (usually through an industry-sponsored course) can allow individuals an opportunity to offer a unique or distinctive service to their community. In addition, as further clinical expertise is gained, the relationship can be expanded to offer local, regional, or even national training courses to colleagues via either on-site or virtual courses. Similarly, opportunities to speak about or demonstrate the technology/technique at educational courses may also follow.
Navigating and expanding the relationship
Once an individual establishes a relationship with a company or has established a reputation as a key opinion leader, additional opportunities for engagement may become available. These include serving as a consultant, becoming a member of an advisory board, participating or directing educational courses for trainees/practitioners, or serving as the principal investigator of a future clinical trial. Serving as a consultant can be quite rewarding as it can highlight clinical needs, identify where product improvement can be achieved, and focus where research and development funds should be directed. Serving on the advisory board can afford an even higher level of influence where corporate strategy can be influenced. Such input is particularly impactful with smaller companies looking to enter a new field or expand a limited market share. There are also a variety of educational opportunities offered by industry including local, regional, and national courses that focus on utilizing a new technology or education concerning a specific disease state. These courses can be held locally at the physician’s clinical site or off site to attract the desired target audience. Finally, being involved in research studies, especially early-stage projects, can be critical as many small companies have limited capital, and it is essential for them to design studies with appropriate endpoints that will ideally achieve both regulatory approval as well as payor coverage. Of note, in addition to relationships directly involving industry, the American Gastroenterological Association Center for GI Innovation and Technology (CGIT) also offers the opportunity to be part of key opinion leader meetings arranged and organized by the AGA. This may allow for some individuals to participate who may be restricted from direct relationships with industry partners. The industry services offered by the CGIT also include clinical trial design and registry management services.
Entrepreneurship/intellectual property
A less commonly explored opportunity with industry involves the development of one’s own intellectual property. Some of the most impactful technologies in my advanced endoscopy clinical practice have been developed from the ideas of gastroenterology colleagues that have been successfully commercialized. These include radiofrequency ablation technology to treat Barrett’s esophagus and the development of lumen-apposing stents. There are several options for physicians with an idea for an innovation. These can include working with a university technology transfer department if they are in an academic setting, creation of their own company, or collaborating with industry to develop the device through a licensing/royalty agreement. The AGA CGIT offers extensive resources to physicians with new ideas on how to secure their intellectual property as well as to evaluate the feasibility of the aforementioned options to choose which may be most appropriate for them.
Important caveats
It is important that physicians with industry relations be aware of their local institutional policies. Some institutions may prohibit such activities while others may limit the types of relationships or the amount of income that can be received. It is the physician’s responsibility to be aware of their institution’s guidelines prior to formalizing industry agreements. If intellectual property is involved, it is essential to know the specific rules regarding physician remuneration, especially pertaining to royalty or equity agreements. Furthermore, with regard to presentations and publications, it is required to acknowledge industry relations and potential conflicts of interest. Failure to do so may adversely affect an individual’s reputation as well as lead to additional consequences such as the potential for retraction of publications or restrictions regarding future educational speaking opportunities. In addition, key opinion leaders often consult for several companies that may be in competition with each other. Therefore, it is essential that there is no disclosure of confidential proprietary information among companies. Finally, the financial incentives resulting from industry collaboration should never influence physician judgment when interpreting or speaking about data regarding product efficacy or safety.
Conclusions
In summary, there are numerous opportunities for physicians to collaborate with industry. These relationships can be very rewarding and can serve to expedite the introduction of new diagnostic or treatment modalities and provide the opportunity to network and interact with colleagues as well as to participate in important research that improves clinical practice. The nature of these relationships should always be transparent, and it is the physician’s responsibility to ensure that the types of relationships that are engaged in are permitted by their employer. Over the course of my career, I have participated in nearly all forms of these relationships and have seen that participation lead to important publications, changes in corporate strategy, the fostering of acquisitions, and the rapid development and utilization of new endoscopic technologies. It is my personal belief than industry relationships can improve professional satisfaction, enhance one’s brand, and most importantly, expedite clinical innovation to improve patient care.
Dr. Muthusamy is professor of clinical medicine at the University of California, Los Angeles, and medical director of endoscopy, UCLA Health System. He disclosed ties with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.
Over half of ED visits from cancer patients could be prevented
Overall, researchers found that 18.3 million (52%) ED visits among patients with cancer between 2012 and 2019 were potentially avoidable. Pain was the most common reason for such a visit. Notably, the number of potentially preventable ED visits documented each year increased over the study period.
“These findings highlight the need for cancer care programs to implement evidence-based interventions to better manage cancer treatment complications, such as uncontrolled pain, in outpatient and ambulatory settings,” said the authors, led by Amir Alishahi Tabriz, MD, PhD, MPH, department of health outcomes and behavior, Moffitt Cancer Center, Tampa.
Authors of an accompanying editorial agree, noting that “patients at risk for having uncontrolled pain could potentially be identified earlier, and steps could be taken that would address their pain and help prevent acute care visits.”
The study and the editorial were published online Jan. 19, 2022, in JAMA Network Open.
Patients with cancer experience a range of side effects from their cancer and treatment. Many such problems can be managed in the ambulatory setting but are often managed in the ED, which is far from optimal for patients with cancer from both a complications and cost perspective. Still, little is known about whether ED visits among patients with cancer are avoidable.
To better understand unnecessary emergency care use by these patients, Dr. Tabriz and colleagues evaluated trends and characteristics of potentially preventable ED visits among adults with cancer who had an ED visit between 2012 and 2019. The authors used the Centers for Medicare & Medicaid Services definition for a potentially preventable ED visit among patients receiving chemotherapy.
Among the 35.5 million ED visits made by patients with cancer during the study period, 18.3 million (52%) were identified as potentially preventable. Nearly 5.8 million of these visits (21%) were classified as being of “high acuity,” and almost 30% resulted in unplanned hospitalizations.
Pain was the most common reason for potentially preventable ED visits, accounting for 37% of these visits.
The absolute number of potentially preventable ED visits among cancer patients increased from about 1.8 million in 2012 to 3.2 million in 2019. The number of patients who visited the ED because of pain more than doubled, from roughly 1.2 million in 2012 to 2.4 million in 2019.
“The disproportionate increase in the number of ED visits by patients with cancer has put a substantial burden on EDs that are already operating at peak capacity” and “reinforces the need for cancer care programs to devise innovative ways to manage complications associated with cancer treatment in the outpatient and ambulatory settings,” Dr. Tabriz and coauthors wrote.
The increase could be an “unintended” consequence of efforts to decrease overall opioid administration in response to the opioid epidemic, Dr. Tabriz and colleagues noted. For example, the authors point to a recent study that found that about half of patients with cancer who had severe pain did not receive outpatient opioids in the week before visiting the ED.
“Even access to outpatient care does not mean patients can get the care they need outside an ED,” wrote editorialists Erek Majka, MD, with Summerlin Hospital, Las Vegas, and N. Seth Trueger, MD, MPH, with Northwestern University, Chicago. Thus, “it is no surprise that patients are sent to the ED if the alternatives do not have the staff or diagnostic and therapeutic capabilities the patients need.”
Overall, however, the “goal is not to eliminate ED visits for their own sake; rather, the goal is better care of patients with cancer, and secondarily, in a manner that is cost-effective,” Dr. Majka and Dr. Trueger explained.
No specific funding for the study was reported. The authors disclosed no relevant financial relationships. Dr. Trueger is digital media editor of JAMA Network Open, but he was not involved in decisions regarding review of the manuscript or its acceptance.
A version of this article first appeared on Medscape.com.
Overall, researchers found that 18.3 million (52%) ED visits among patients with cancer between 2012 and 2019 were potentially avoidable. Pain was the most common reason for such a visit. Notably, the number of potentially preventable ED visits documented each year increased over the study period.
“These findings highlight the need for cancer care programs to implement evidence-based interventions to better manage cancer treatment complications, such as uncontrolled pain, in outpatient and ambulatory settings,” said the authors, led by Amir Alishahi Tabriz, MD, PhD, MPH, department of health outcomes and behavior, Moffitt Cancer Center, Tampa.
Authors of an accompanying editorial agree, noting that “patients at risk for having uncontrolled pain could potentially be identified earlier, and steps could be taken that would address their pain and help prevent acute care visits.”
The study and the editorial were published online Jan. 19, 2022, in JAMA Network Open.
Patients with cancer experience a range of side effects from their cancer and treatment. Many such problems can be managed in the ambulatory setting but are often managed in the ED, which is far from optimal for patients with cancer from both a complications and cost perspective. Still, little is known about whether ED visits among patients with cancer are avoidable.
To better understand unnecessary emergency care use by these patients, Dr. Tabriz and colleagues evaluated trends and characteristics of potentially preventable ED visits among adults with cancer who had an ED visit between 2012 and 2019. The authors used the Centers for Medicare & Medicaid Services definition for a potentially preventable ED visit among patients receiving chemotherapy.
Among the 35.5 million ED visits made by patients with cancer during the study period, 18.3 million (52%) were identified as potentially preventable. Nearly 5.8 million of these visits (21%) were classified as being of “high acuity,” and almost 30% resulted in unplanned hospitalizations.
Pain was the most common reason for potentially preventable ED visits, accounting for 37% of these visits.
The absolute number of potentially preventable ED visits among cancer patients increased from about 1.8 million in 2012 to 3.2 million in 2019. The number of patients who visited the ED because of pain more than doubled, from roughly 1.2 million in 2012 to 2.4 million in 2019.
“The disproportionate increase in the number of ED visits by patients with cancer has put a substantial burden on EDs that are already operating at peak capacity” and “reinforces the need for cancer care programs to devise innovative ways to manage complications associated with cancer treatment in the outpatient and ambulatory settings,” Dr. Tabriz and coauthors wrote.
The increase could be an “unintended” consequence of efforts to decrease overall opioid administration in response to the opioid epidemic, Dr. Tabriz and colleagues noted. For example, the authors point to a recent study that found that about half of patients with cancer who had severe pain did not receive outpatient opioids in the week before visiting the ED.
“Even access to outpatient care does not mean patients can get the care they need outside an ED,” wrote editorialists Erek Majka, MD, with Summerlin Hospital, Las Vegas, and N. Seth Trueger, MD, MPH, with Northwestern University, Chicago. Thus, “it is no surprise that patients are sent to the ED if the alternatives do not have the staff or diagnostic and therapeutic capabilities the patients need.”
Overall, however, the “goal is not to eliminate ED visits for their own sake; rather, the goal is better care of patients with cancer, and secondarily, in a manner that is cost-effective,” Dr. Majka and Dr. Trueger explained.
No specific funding for the study was reported. The authors disclosed no relevant financial relationships. Dr. Trueger is digital media editor of JAMA Network Open, but he was not involved in decisions regarding review of the manuscript or its acceptance.
A version of this article first appeared on Medscape.com.
Overall, researchers found that 18.3 million (52%) ED visits among patients with cancer between 2012 and 2019 were potentially avoidable. Pain was the most common reason for such a visit. Notably, the number of potentially preventable ED visits documented each year increased over the study period.
“These findings highlight the need for cancer care programs to implement evidence-based interventions to better manage cancer treatment complications, such as uncontrolled pain, in outpatient and ambulatory settings,” said the authors, led by Amir Alishahi Tabriz, MD, PhD, MPH, department of health outcomes and behavior, Moffitt Cancer Center, Tampa.
Authors of an accompanying editorial agree, noting that “patients at risk for having uncontrolled pain could potentially be identified earlier, and steps could be taken that would address their pain and help prevent acute care visits.”
The study and the editorial were published online Jan. 19, 2022, in JAMA Network Open.
Patients with cancer experience a range of side effects from their cancer and treatment. Many such problems can be managed in the ambulatory setting but are often managed in the ED, which is far from optimal for patients with cancer from both a complications and cost perspective. Still, little is known about whether ED visits among patients with cancer are avoidable.
To better understand unnecessary emergency care use by these patients, Dr. Tabriz and colleagues evaluated trends and characteristics of potentially preventable ED visits among adults with cancer who had an ED visit between 2012 and 2019. The authors used the Centers for Medicare & Medicaid Services definition for a potentially preventable ED visit among patients receiving chemotherapy.
Among the 35.5 million ED visits made by patients with cancer during the study period, 18.3 million (52%) were identified as potentially preventable. Nearly 5.8 million of these visits (21%) were classified as being of “high acuity,” and almost 30% resulted in unplanned hospitalizations.
Pain was the most common reason for potentially preventable ED visits, accounting for 37% of these visits.
The absolute number of potentially preventable ED visits among cancer patients increased from about 1.8 million in 2012 to 3.2 million in 2019. The number of patients who visited the ED because of pain more than doubled, from roughly 1.2 million in 2012 to 2.4 million in 2019.
“The disproportionate increase in the number of ED visits by patients with cancer has put a substantial burden on EDs that are already operating at peak capacity” and “reinforces the need for cancer care programs to devise innovative ways to manage complications associated with cancer treatment in the outpatient and ambulatory settings,” Dr. Tabriz and coauthors wrote.
The increase could be an “unintended” consequence of efforts to decrease overall opioid administration in response to the opioid epidemic, Dr. Tabriz and colleagues noted. For example, the authors point to a recent study that found that about half of patients with cancer who had severe pain did not receive outpatient opioids in the week before visiting the ED.
“Even access to outpatient care does not mean patients can get the care they need outside an ED,” wrote editorialists Erek Majka, MD, with Summerlin Hospital, Las Vegas, and N. Seth Trueger, MD, MPH, with Northwestern University, Chicago. Thus, “it is no surprise that patients are sent to the ED if the alternatives do not have the staff or diagnostic and therapeutic capabilities the patients need.”
Overall, however, the “goal is not to eliminate ED visits for their own sake; rather, the goal is better care of patients with cancer, and secondarily, in a manner that is cost-effective,” Dr. Majka and Dr. Trueger explained.
No specific funding for the study was reported. The authors disclosed no relevant financial relationships. Dr. Trueger is digital media editor of JAMA Network Open, but he was not involved in decisions regarding review of the manuscript or its acceptance.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Concern grows over ‘medical assistance in dying for mental illness’ law
Canada already has the largest number of deaths by MAID of any nation, with 10,064 in 2021, a 32% increase from 2020. With the addition of serious mental illness (SMI) as an eligible category, the country is on track to have the most liberal assisted-death policy in the world.
Concerns about the additional number of patients who could become eligible for MAID, and a lack of evidence-backed standards from disability rights groups, mental health advocates, First Nations leaders, psychiatrists, and other mental health providers, seems to have led the Canadian government to give the proposed law some sober second thought.
“Listening to experts and Canadians, we believe this date needs to be temporarily delayed,” said David Lametti, Canada’s minister of Justice and attorney general of Canada; Jean-Yves Duclos, minister of Health; and Carolyn Bennett, minister of Mental Health and Addictions, in a Dec. 15, 2022, joint statement.
Canada’s Parliament – which approved the expansion – will now have to vote on whether to okay a pause on the legislation.
However, the Canadian Psychiatric Association has not been calling for a delay in the proposed legislation. In a November 2021 statement, the CPA said it “does not take a position on the legality or morality of MAID,” but added that to deny MAID to people with mental illness was discriminatory, and that, as it was the law, it must be followed.
“CPA has not taken a position about MAID,” the association’s president Gary Chaimowitz, MBChB, told this news organization. “We know this is coming and our organization is trying to get its members ready for what will be most likely the ability of people with mental conditions to be able to request MAID,” said Dr. Chaimowitz, who is also head of forensic psychiatry at St. Joseph’s Healthcare and a professor of psychiatry at McMaster University, both in Hamilton, Ont.
Dr. Chaimowitz acknowledges that “a majority of psychiatrists do not want to be involved in anything to do with MAID.”
“The idea, certainly in psychiatry, is to get people well and we’ve been taught that people dying from a major mental disorder is something that we’re trained to prevent,” he added.
A ‘clinical option’
Assisted medical death is especially fraught in psychiatry, said Rebecca Brendel, MD, president of the American Psychiatric Association. She noted a 25-year life expectancy gap between people with SMI and those who do not have such conditions.
“As a profession we have very serious obligations to advance treatment so that a person with serious mental illness can live [a] full, productive, and healthy [life],” Dr. Brendel, associate director of the Center for Bioethics at Harvard Medical School in Boston, said in an interview.
Under the Canadian proposal, psychiatrists would be allowed to suggest MAID as a “clinical option.”
Harold Braswell, PhD, a fellow with The Hastings Center, a bioethics research institute, calls that problematic.
“It’s not neutral to suggest to someone that it would be theoretically reasonable to end their lives,” Dr. Braswell, associate professor at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University, told this news organization.
It also creates a double standard in the treatment of suicidal ideation, in which suicide prevention is absolute for some, but encouraging it as a possibility for others, he added.
“To have that come from an authority figure is something that’s very harsh and, in my opinion, very potentially destructive,” especially for vulnerable groups, like First Nations people, who already have elevated rates of suicide, said Dr. Braswell.
Fierce debate
Since 2016, Canada has allowed MAID for medical conditions and diseases that will not improve and in cases where the evidence shows that medical providers can accurately predict the condition will not improve.
However, in 2019, a Quebec court ruled that the law unconstitutionally barred euthanasia in people who were not terminally ill. In March 2021, Canada’s criminal code was amended to allow MAID for people whose natural death was not “reasonably foreseeable,” but it excluded SMI for a period of 2 years, ending in March 2023.
The 2-year stay was intended to allow for study and to give mental health providers and MAID assessors time to develop standards.
The federal government charged a 12-member expert panel with determining how to safely allow MAID for SMI. In its final report released in May 2022 it recommended that standards be developed.
The panel acknowledged that for many conditions it may be impossible to make predictions about whether an individual might improve. However, it did not mention SMI.
In those cases, when MAID is requested, “establishing incurability and irreversibility on the basis of the evolution and response to past interventions is necessary,” the panel noted, adding that these are the criteria used by psychiatrists assessing euthanasia requests in the Netherlands and Belgium.
But the notion that mental illness can be irremediable has been fiercely debated.
Soon after the expert report was released, the Center for Addiction and Mental Health in Toronto noted on its website that there are currently “no agreed upon standards for psychiatrists or other health care practitioners to use to determine if a person’s mental illness is ‘grievous and irremediable’ for the purposes of MAID.”
Dr. Chaimowitz acknowledged that “there’s no agreed-upon definition of incurability” in mental illness. Some psychiatrists “will argue that there’s always another treatment that can be attempted,” he said, adding that there has been a lack of consensus on irremediability among CPA members.
Protecting vulnerable populations
Matt Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, said the question of irremediability is crucial. “Most people with mental illness do get better, especially if they’re in treatment,” Dr. Wynia said.
For MAID assessors it may be difficult to know when someone has tried all possible treatments, especially given the wide array of options, including psychedelics, said Dr. Wynia.
Dr. Braswell said there is not enough evidence that mental illness is incurable. With SMI, “there’s a lot more potential for the causes of the individual’s suffering to be ameliorated. By offering MAID, you’re going to kill people who might have been able to get out of this through other nonlethal means.”
Currently, MAID is provided for an irremediable medical condition, “in other words, a condition that will not improve and that we can predict will not improve,” said Karandeep S. Gaind, MD, chief of psychiatry at Toronto’s Humber River Hospital and physician chair of the hospital’s MAID team.
“If that’s the premise, then I think we cannot provide MAID for sole mental illness,” Dr. Gaind said. “Because we can’t honestly make those predictions” with mental illness, he added.
Dr. Gaind does not support MAID for mental illness and believes that it will put the vulnerable – including those living in poverty – at particular risk.
With the proposed expansion, MAID is “now becoming something which is being sought as a way to escape a painful life rather than to avoid a painful death,” said Dr. Gaind, who is also a past president of the CPA.
One member of the federal government’s expert panel – Ellen Cohen, who had a psychiatric condition – wrote in The Globe and Mail that she quit early on when it became apparent that the panel was not seriously considering her own experiences or the possibility that poverty and lack of access to care or social supports could strongly influence a request for MAID.
Social determinants of suffering
People with mental illness often are without homes, have substance use disorders, have been stigmatized and discriminated against, and have poor social supports, said Dr. Wynia. “You worry that it’s all of those things that are making them want to end their lives,” he said.
The Daily Mail ran a story in December 2022 about a 65-year-old Canadian who said he’d applied for MAID solely because of fears that his disability benefits for various chronic health conditions were being cut off and that he didn’t want to live in poverty.
A 51-year-old Ontario woman with multiple chemical sensitivities was granted MAID after she said she could not find housing that could keep her safe, according to an August report by CTV News.
Tarek Rajji, MD, chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH, said social determinants of health need to be considered in standards created to guide MAID for mental illness.
“We’re very mindful of the fact that the suffering, that is, the grievousness that the person is living with, in the context of mental illness, many times is due to the social determinants of their illness and the social determinants of their suffering,” Dr. Rajji said.
Many are also concerned that it will be difficult to separate out suicidality from sheer hopelessness.
The CPA has advised a group that’s working on developing guidelines for MAID in SMI and is also developing a curriculum for mental health providers, Dr. Chaimowitz said. As part of that, there will be a process to ensure that someone who is actively suicidal is not granted MAID.
“I do not believe that it’s contemplated that MAID is going to accelerate or facilitate suicidal ideation,” he said. Someone who is suicidal will be referred to treatment, said Dr. Chaimowitz.
“People with depression often feel hopeless,” and may refuse treatments that have worked in the past, countered Dr. Gaind. Some of his patients “are absolutely convinced that nothing will help,” he said.
Troublesome cases
The expert panel said in its final report that “it is not possible to provide fixed rules for how many attempts at interventions, how many types of interventions, and over how much time,” are necessary to establish “irreversibility” of mental illness.
Dr. Chaimowitz said MAID will not be offered to anyone “refusing treatment for their condition without any good reason.” They will be “unlikely to meet criteria for incurable,” as they will have needed to avail themselves of the array of treatments available, he said.
That would be similar to rules in Belgium and the Netherlands, which allow euthanasia for psychiatric conditions.
An estimated 100-300 psychiatric patients receive euthanasia each year in those countries, according to a 2021 commentary in Psychiatric Times (Jun 7;38[6]) by Mark S. Komrad, MD, a Towson, Maryland-based psychiatrist.
There are still troublesome cases.
As previously reported by this news organization, many in Belgium were distressed recently at the news that a 23-year-old woman who had survived a terrorist attack, Shanti De Corte, requested and was granted euthanasia.
As the deadline for implementation of MAID grew closer, calls for delay grew louder, especially given the lack of concrete standards for providers.
During the waning months of 2022, Dr. Gaind – who said he was suspended from CPA for “unprofessional interactions” and allegedly misrepresenting CPA’s processes and governance matters – announced the launch of a new organization, the Society of Canadian Psychiatry, in November calling for a delay in MAID of at least 1 year so that evidence-based safeguards could be implemented. The petition has been signed by more than 200 psychiatrists, along with several dozen physicians, MAID assessors, and individuals with mental illness and family members.
The Association of Chairs of Psychiatry in Canada, the Canadian Association for Suicide Prevention, the Council of Canadians with Disabilities, a group of indigenous leaders, and the Ontario Association for ACT and FACT, psychiatrists who provide care to individuals with severe mental illness, among other groups, joined the call for a delay.
In its December announcement, the Canadian federal ministers said a factor in seeking a delay was that standards guiding clinicians would not be delivered until at least February – too close to when applications would be opened.
Upon hearing about the federal government’s intentions, the chair of the expert panel, Mona Gupta, MD, told The Canadian Press that she did not think it was necessary to put off implementation because necessary safeguards were already in place.
Dr. Chaimowitz awaits the standards but is optimistic that for mental illness, “the process will be tightly controlled, closely monitored, and open to scrutiny,” he said.
Dr. Braswell is not convinced. The concern is that adding people with mental illness is “going to overload the capacity of the government to monitor this practice,” he said.
Is the United States next?
Although Canada and the United States share a border, it’s unlikely that U.S. states will allow aid in dying for nonterminal illness, much less for psychiatric conditions any time soon, said Dr. Braswell and others.
Ten states – California, Colorado, Hawaii, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, and Washington – have laws allowing assistance in dying, but for terminal illness only.
In 2016, the APA adopted the American Medical Association policy on medical euthanasia, stating, “that a psychiatrist should not prescribe or administer any intervention to a nonterminally ill person for the purpose of causing death.”
Dr. Brendel said the field is acutely aware that people with mental illness do suffer, but that more work needs to be done – and is being done – on “distinguishing wishes to hasten death or end one’s life from these historical or traditional notions that any premature death is a suicide.”
There is also increasing discussion within the medical community, not just psychiatry, about a physician’s duty to relieve suffering, said Dr. Wynia. “There’s debate basically about whether we stand for preserving life essentially at all costs and never being involved in the taking of life, or whether we stand for reduction of suffering and being the advocate for the patients that we serve,” he said.
“Those are both legitimate,” said Dr. Wynia, adding, “there are good reasons to want both of those to be true.”
“I suspect that 20 years from now we will still be having conversations about how physicians, how psychiatrists ought to participate in preserving life and in shepherding death,” said Dr. Brendel.
But to Dr. Gaind, the debate is not just esoteric, it’s a soon-to-be reality in Canada. “When we’re providing death to people who aren’t dying, to me that’s like providing what amounts to a wrongful death,” he said.
A version of this article originally appeared on Medscape.com.
Canada already has the largest number of deaths by MAID of any nation, with 10,064 in 2021, a 32% increase from 2020. With the addition of serious mental illness (SMI) as an eligible category, the country is on track to have the most liberal assisted-death policy in the world.
Concerns about the additional number of patients who could become eligible for MAID, and a lack of evidence-backed standards from disability rights groups, mental health advocates, First Nations leaders, psychiatrists, and other mental health providers, seems to have led the Canadian government to give the proposed law some sober second thought.
“Listening to experts and Canadians, we believe this date needs to be temporarily delayed,” said David Lametti, Canada’s minister of Justice and attorney general of Canada; Jean-Yves Duclos, minister of Health; and Carolyn Bennett, minister of Mental Health and Addictions, in a Dec. 15, 2022, joint statement.
Canada’s Parliament – which approved the expansion – will now have to vote on whether to okay a pause on the legislation.
However, the Canadian Psychiatric Association has not been calling for a delay in the proposed legislation. In a November 2021 statement, the CPA said it “does not take a position on the legality or morality of MAID,” but added that to deny MAID to people with mental illness was discriminatory, and that, as it was the law, it must be followed.
“CPA has not taken a position about MAID,” the association’s president Gary Chaimowitz, MBChB, told this news organization. “We know this is coming and our organization is trying to get its members ready for what will be most likely the ability of people with mental conditions to be able to request MAID,” said Dr. Chaimowitz, who is also head of forensic psychiatry at St. Joseph’s Healthcare and a professor of psychiatry at McMaster University, both in Hamilton, Ont.
Dr. Chaimowitz acknowledges that “a majority of psychiatrists do not want to be involved in anything to do with MAID.”
“The idea, certainly in psychiatry, is to get people well and we’ve been taught that people dying from a major mental disorder is something that we’re trained to prevent,” he added.
A ‘clinical option’
Assisted medical death is especially fraught in psychiatry, said Rebecca Brendel, MD, president of the American Psychiatric Association. She noted a 25-year life expectancy gap between people with SMI and those who do not have such conditions.
“As a profession we have very serious obligations to advance treatment so that a person with serious mental illness can live [a] full, productive, and healthy [life],” Dr. Brendel, associate director of the Center for Bioethics at Harvard Medical School in Boston, said in an interview.
Under the Canadian proposal, psychiatrists would be allowed to suggest MAID as a “clinical option.”
Harold Braswell, PhD, a fellow with The Hastings Center, a bioethics research institute, calls that problematic.
“It’s not neutral to suggest to someone that it would be theoretically reasonable to end their lives,” Dr. Braswell, associate professor at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University, told this news organization.
It also creates a double standard in the treatment of suicidal ideation, in which suicide prevention is absolute for some, but encouraging it as a possibility for others, he added.
“To have that come from an authority figure is something that’s very harsh and, in my opinion, very potentially destructive,” especially for vulnerable groups, like First Nations people, who already have elevated rates of suicide, said Dr. Braswell.
Fierce debate
Since 2016, Canada has allowed MAID for medical conditions and diseases that will not improve and in cases where the evidence shows that medical providers can accurately predict the condition will not improve.
However, in 2019, a Quebec court ruled that the law unconstitutionally barred euthanasia in people who were not terminally ill. In March 2021, Canada’s criminal code was amended to allow MAID for people whose natural death was not “reasonably foreseeable,” but it excluded SMI for a period of 2 years, ending in March 2023.
The 2-year stay was intended to allow for study and to give mental health providers and MAID assessors time to develop standards.
The federal government charged a 12-member expert panel with determining how to safely allow MAID for SMI. In its final report released in May 2022 it recommended that standards be developed.
The panel acknowledged that for many conditions it may be impossible to make predictions about whether an individual might improve. However, it did not mention SMI.
In those cases, when MAID is requested, “establishing incurability and irreversibility on the basis of the evolution and response to past interventions is necessary,” the panel noted, adding that these are the criteria used by psychiatrists assessing euthanasia requests in the Netherlands and Belgium.
But the notion that mental illness can be irremediable has been fiercely debated.
Soon after the expert report was released, the Center for Addiction and Mental Health in Toronto noted on its website that there are currently “no agreed upon standards for psychiatrists or other health care practitioners to use to determine if a person’s mental illness is ‘grievous and irremediable’ for the purposes of MAID.”
Dr. Chaimowitz acknowledged that “there’s no agreed-upon definition of incurability” in mental illness. Some psychiatrists “will argue that there’s always another treatment that can be attempted,” he said, adding that there has been a lack of consensus on irremediability among CPA members.
Protecting vulnerable populations
Matt Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, said the question of irremediability is crucial. “Most people with mental illness do get better, especially if they’re in treatment,” Dr. Wynia said.
For MAID assessors it may be difficult to know when someone has tried all possible treatments, especially given the wide array of options, including psychedelics, said Dr. Wynia.
Dr. Braswell said there is not enough evidence that mental illness is incurable. With SMI, “there’s a lot more potential for the causes of the individual’s suffering to be ameliorated. By offering MAID, you’re going to kill people who might have been able to get out of this through other nonlethal means.”
Currently, MAID is provided for an irremediable medical condition, “in other words, a condition that will not improve and that we can predict will not improve,” said Karandeep S. Gaind, MD, chief of psychiatry at Toronto’s Humber River Hospital and physician chair of the hospital’s MAID team.
“If that’s the premise, then I think we cannot provide MAID for sole mental illness,” Dr. Gaind said. “Because we can’t honestly make those predictions” with mental illness, he added.
Dr. Gaind does not support MAID for mental illness and believes that it will put the vulnerable – including those living in poverty – at particular risk.
With the proposed expansion, MAID is “now becoming something which is being sought as a way to escape a painful life rather than to avoid a painful death,” said Dr. Gaind, who is also a past president of the CPA.
One member of the federal government’s expert panel – Ellen Cohen, who had a psychiatric condition – wrote in The Globe and Mail that she quit early on when it became apparent that the panel was not seriously considering her own experiences or the possibility that poverty and lack of access to care or social supports could strongly influence a request for MAID.
Social determinants of suffering
People with mental illness often are without homes, have substance use disorders, have been stigmatized and discriminated against, and have poor social supports, said Dr. Wynia. “You worry that it’s all of those things that are making them want to end their lives,” he said.
The Daily Mail ran a story in December 2022 about a 65-year-old Canadian who said he’d applied for MAID solely because of fears that his disability benefits for various chronic health conditions were being cut off and that he didn’t want to live in poverty.
A 51-year-old Ontario woman with multiple chemical sensitivities was granted MAID after she said she could not find housing that could keep her safe, according to an August report by CTV News.
Tarek Rajji, MD, chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH, said social determinants of health need to be considered in standards created to guide MAID for mental illness.
“We’re very mindful of the fact that the suffering, that is, the grievousness that the person is living with, in the context of mental illness, many times is due to the social determinants of their illness and the social determinants of their suffering,” Dr. Rajji said.
Many are also concerned that it will be difficult to separate out suicidality from sheer hopelessness.
The CPA has advised a group that’s working on developing guidelines for MAID in SMI and is also developing a curriculum for mental health providers, Dr. Chaimowitz said. As part of that, there will be a process to ensure that someone who is actively suicidal is not granted MAID.
“I do not believe that it’s contemplated that MAID is going to accelerate or facilitate suicidal ideation,” he said. Someone who is suicidal will be referred to treatment, said Dr. Chaimowitz.
“People with depression often feel hopeless,” and may refuse treatments that have worked in the past, countered Dr. Gaind. Some of his patients “are absolutely convinced that nothing will help,” he said.
Troublesome cases
The expert panel said in its final report that “it is not possible to provide fixed rules for how many attempts at interventions, how many types of interventions, and over how much time,” are necessary to establish “irreversibility” of mental illness.
Dr. Chaimowitz said MAID will not be offered to anyone “refusing treatment for their condition without any good reason.” They will be “unlikely to meet criteria for incurable,” as they will have needed to avail themselves of the array of treatments available, he said.
That would be similar to rules in Belgium and the Netherlands, which allow euthanasia for psychiatric conditions.
An estimated 100-300 psychiatric patients receive euthanasia each year in those countries, according to a 2021 commentary in Psychiatric Times (Jun 7;38[6]) by Mark S. Komrad, MD, a Towson, Maryland-based psychiatrist.
There are still troublesome cases.
As previously reported by this news organization, many in Belgium were distressed recently at the news that a 23-year-old woman who had survived a terrorist attack, Shanti De Corte, requested and was granted euthanasia.
As the deadline for implementation of MAID grew closer, calls for delay grew louder, especially given the lack of concrete standards for providers.
During the waning months of 2022, Dr. Gaind – who said he was suspended from CPA for “unprofessional interactions” and allegedly misrepresenting CPA’s processes and governance matters – announced the launch of a new organization, the Society of Canadian Psychiatry, in November calling for a delay in MAID of at least 1 year so that evidence-based safeguards could be implemented. The petition has been signed by more than 200 psychiatrists, along with several dozen physicians, MAID assessors, and individuals with mental illness and family members.
The Association of Chairs of Psychiatry in Canada, the Canadian Association for Suicide Prevention, the Council of Canadians with Disabilities, a group of indigenous leaders, and the Ontario Association for ACT and FACT, psychiatrists who provide care to individuals with severe mental illness, among other groups, joined the call for a delay.
In its December announcement, the Canadian federal ministers said a factor in seeking a delay was that standards guiding clinicians would not be delivered until at least February – too close to when applications would be opened.
Upon hearing about the federal government’s intentions, the chair of the expert panel, Mona Gupta, MD, told The Canadian Press that she did not think it was necessary to put off implementation because necessary safeguards were already in place.
Dr. Chaimowitz awaits the standards but is optimistic that for mental illness, “the process will be tightly controlled, closely monitored, and open to scrutiny,” he said.
Dr. Braswell is not convinced. The concern is that adding people with mental illness is “going to overload the capacity of the government to monitor this practice,” he said.
Is the United States next?
Although Canada and the United States share a border, it’s unlikely that U.S. states will allow aid in dying for nonterminal illness, much less for psychiatric conditions any time soon, said Dr. Braswell and others.
Ten states – California, Colorado, Hawaii, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, and Washington – have laws allowing assistance in dying, but for terminal illness only.
In 2016, the APA adopted the American Medical Association policy on medical euthanasia, stating, “that a psychiatrist should not prescribe or administer any intervention to a nonterminally ill person for the purpose of causing death.”
Dr. Brendel said the field is acutely aware that people with mental illness do suffer, but that more work needs to be done – and is being done – on “distinguishing wishes to hasten death or end one’s life from these historical or traditional notions that any premature death is a suicide.”
There is also increasing discussion within the medical community, not just psychiatry, about a physician’s duty to relieve suffering, said Dr. Wynia. “There’s debate basically about whether we stand for preserving life essentially at all costs and never being involved in the taking of life, or whether we stand for reduction of suffering and being the advocate for the patients that we serve,” he said.
“Those are both legitimate,” said Dr. Wynia, adding, “there are good reasons to want both of those to be true.”
“I suspect that 20 years from now we will still be having conversations about how physicians, how psychiatrists ought to participate in preserving life and in shepherding death,” said Dr. Brendel.
But to Dr. Gaind, the debate is not just esoteric, it’s a soon-to-be reality in Canada. “When we’re providing death to people who aren’t dying, to me that’s like providing what amounts to a wrongful death,” he said.
A version of this article originally appeared on Medscape.com.
Canada already has the largest number of deaths by MAID of any nation, with 10,064 in 2021, a 32% increase from 2020. With the addition of serious mental illness (SMI) as an eligible category, the country is on track to have the most liberal assisted-death policy in the world.
Concerns about the additional number of patients who could become eligible for MAID, and a lack of evidence-backed standards from disability rights groups, mental health advocates, First Nations leaders, psychiatrists, and other mental health providers, seems to have led the Canadian government to give the proposed law some sober second thought.
“Listening to experts and Canadians, we believe this date needs to be temporarily delayed,” said David Lametti, Canada’s minister of Justice and attorney general of Canada; Jean-Yves Duclos, minister of Health; and Carolyn Bennett, minister of Mental Health and Addictions, in a Dec. 15, 2022, joint statement.
Canada’s Parliament – which approved the expansion – will now have to vote on whether to okay a pause on the legislation.
However, the Canadian Psychiatric Association has not been calling for a delay in the proposed legislation. In a November 2021 statement, the CPA said it “does not take a position on the legality or morality of MAID,” but added that to deny MAID to people with mental illness was discriminatory, and that, as it was the law, it must be followed.
“CPA has not taken a position about MAID,” the association’s president Gary Chaimowitz, MBChB, told this news organization. “We know this is coming and our organization is trying to get its members ready for what will be most likely the ability of people with mental conditions to be able to request MAID,” said Dr. Chaimowitz, who is also head of forensic psychiatry at St. Joseph’s Healthcare and a professor of psychiatry at McMaster University, both in Hamilton, Ont.
Dr. Chaimowitz acknowledges that “a majority of psychiatrists do not want to be involved in anything to do with MAID.”
“The idea, certainly in psychiatry, is to get people well and we’ve been taught that people dying from a major mental disorder is something that we’re trained to prevent,” he added.
A ‘clinical option’
Assisted medical death is especially fraught in psychiatry, said Rebecca Brendel, MD, president of the American Psychiatric Association. She noted a 25-year life expectancy gap between people with SMI and those who do not have such conditions.
“As a profession we have very serious obligations to advance treatment so that a person with serious mental illness can live [a] full, productive, and healthy [life],” Dr. Brendel, associate director of the Center for Bioethics at Harvard Medical School in Boston, said in an interview.
Under the Canadian proposal, psychiatrists would be allowed to suggest MAID as a “clinical option.”
Harold Braswell, PhD, a fellow with The Hastings Center, a bioethics research institute, calls that problematic.
“It’s not neutral to suggest to someone that it would be theoretically reasonable to end their lives,” Dr. Braswell, associate professor at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University, told this news organization.
It also creates a double standard in the treatment of suicidal ideation, in which suicide prevention is absolute for some, but encouraging it as a possibility for others, he added.
“To have that come from an authority figure is something that’s very harsh and, in my opinion, very potentially destructive,” especially for vulnerable groups, like First Nations people, who already have elevated rates of suicide, said Dr. Braswell.
Fierce debate
Since 2016, Canada has allowed MAID for medical conditions and diseases that will not improve and in cases where the evidence shows that medical providers can accurately predict the condition will not improve.
However, in 2019, a Quebec court ruled that the law unconstitutionally barred euthanasia in people who were not terminally ill. In March 2021, Canada’s criminal code was amended to allow MAID for people whose natural death was not “reasonably foreseeable,” but it excluded SMI for a period of 2 years, ending in March 2023.
The 2-year stay was intended to allow for study and to give mental health providers and MAID assessors time to develop standards.
The federal government charged a 12-member expert panel with determining how to safely allow MAID for SMI. In its final report released in May 2022 it recommended that standards be developed.
The panel acknowledged that for many conditions it may be impossible to make predictions about whether an individual might improve. However, it did not mention SMI.
In those cases, when MAID is requested, “establishing incurability and irreversibility on the basis of the evolution and response to past interventions is necessary,” the panel noted, adding that these are the criteria used by psychiatrists assessing euthanasia requests in the Netherlands and Belgium.
But the notion that mental illness can be irremediable has been fiercely debated.
Soon after the expert report was released, the Center for Addiction and Mental Health in Toronto noted on its website that there are currently “no agreed upon standards for psychiatrists or other health care practitioners to use to determine if a person’s mental illness is ‘grievous and irremediable’ for the purposes of MAID.”
Dr. Chaimowitz acknowledged that “there’s no agreed-upon definition of incurability” in mental illness. Some psychiatrists “will argue that there’s always another treatment that can be attempted,” he said, adding that there has been a lack of consensus on irremediability among CPA members.
Protecting vulnerable populations
Matt Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, said the question of irremediability is crucial. “Most people with mental illness do get better, especially if they’re in treatment,” Dr. Wynia said.
For MAID assessors it may be difficult to know when someone has tried all possible treatments, especially given the wide array of options, including psychedelics, said Dr. Wynia.
Dr. Braswell said there is not enough evidence that mental illness is incurable. With SMI, “there’s a lot more potential for the causes of the individual’s suffering to be ameliorated. By offering MAID, you’re going to kill people who might have been able to get out of this through other nonlethal means.”
Currently, MAID is provided for an irremediable medical condition, “in other words, a condition that will not improve and that we can predict will not improve,” said Karandeep S. Gaind, MD, chief of psychiatry at Toronto’s Humber River Hospital and physician chair of the hospital’s MAID team.
“If that’s the premise, then I think we cannot provide MAID for sole mental illness,” Dr. Gaind said. “Because we can’t honestly make those predictions” with mental illness, he added.
Dr. Gaind does not support MAID for mental illness and believes that it will put the vulnerable – including those living in poverty – at particular risk.
With the proposed expansion, MAID is “now becoming something which is being sought as a way to escape a painful life rather than to avoid a painful death,” said Dr. Gaind, who is also a past president of the CPA.
One member of the federal government’s expert panel – Ellen Cohen, who had a psychiatric condition – wrote in The Globe and Mail that she quit early on when it became apparent that the panel was not seriously considering her own experiences or the possibility that poverty and lack of access to care or social supports could strongly influence a request for MAID.
Social determinants of suffering
People with mental illness often are without homes, have substance use disorders, have been stigmatized and discriminated against, and have poor social supports, said Dr. Wynia. “You worry that it’s all of those things that are making them want to end their lives,” he said.
The Daily Mail ran a story in December 2022 about a 65-year-old Canadian who said he’d applied for MAID solely because of fears that his disability benefits for various chronic health conditions were being cut off and that he didn’t want to live in poverty.
A 51-year-old Ontario woman with multiple chemical sensitivities was granted MAID after she said she could not find housing that could keep her safe, according to an August report by CTV News.
Tarek Rajji, MD, chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH, said social determinants of health need to be considered in standards created to guide MAID for mental illness.
“We’re very mindful of the fact that the suffering, that is, the grievousness that the person is living with, in the context of mental illness, many times is due to the social determinants of their illness and the social determinants of their suffering,” Dr. Rajji said.
Many are also concerned that it will be difficult to separate out suicidality from sheer hopelessness.
The CPA has advised a group that’s working on developing guidelines for MAID in SMI and is also developing a curriculum for mental health providers, Dr. Chaimowitz said. As part of that, there will be a process to ensure that someone who is actively suicidal is not granted MAID.
“I do not believe that it’s contemplated that MAID is going to accelerate or facilitate suicidal ideation,” he said. Someone who is suicidal will be referred to treatment, said Dr. Chaimowitz.
“People with depression often feel hopeless,” and may refuse treatments that have worked in the past, countered Dr. Gaind. Some of his patients “are absolutely convinced that nothing will help,” he said.
Troublesome cases
The expert panel said in its final report that “it is not possible to provide fixed rules for how many attempts at interventions, how many types of interventions, and over how much time,” are necessary to establish “irreversibility” of mental illness.
Dr. Chaimowitz said MAID will not be offered to anyone “refusing treatment for their condition without any good reason.” They will be “unlikely to meet criteria for incurable,” as they will have needed to avail themselves of the array of treatments available, he said.
That would be similar to rules in Belgium and the Netherlands, which allow euthanasia for psychiatric conditions.
An estimated 100-300 psychiatric patients receive euthanasia each year in those countries, according to a 2021 commentary in Psychiatric Times (Jun 7;38[6]) by Mark S. Komrad, MD, a Towson, Maryland-based psychiatrist.
There are still troublesome cases.
As previously reported by this news organization, many in Belgium were distressed recently at the news that a 23-year-old woman who had survived a terrorist attack, Shanti De Corte, requested and was granted euthanasia.
As the deadline for implementation of MAID grew closer, calls for delay grew louder, especially given the lack of concrete standards for providers.
During the waning months of 2022, Dr. Gaind – who said he was suspended from CPA for “unprofessional interactions” and allegedly misrepresenting CPA’s processes and governance matters – announced the launch of a new organization, the Society of Canadian Psychiatry, in November calling for a delay in MAID of at least 1 year so that evidence-based safeguards could be implemented. The petition has been signed by more than 200 psychiatrists, along with several dozen physicians, MAID assessors, and individuals with mental illness and family members.
The Association of Chairs of Psychiatry in Canada, the Canadian Association for Suicide Prevention, the Council of Canadians with Disabilities, a group of indigenous leaders, and the Ontario Association for ACT and FACT, psychiatrists who provide care to individuals with severe mental illness, among other groups, joined the call for a delay.
In its December announcement, the Canadian federal ministers said a factor in seeking a delay was that standards guiding clinicians would not be delivered until at least February – too close to when applications would be opened.
Upon hearing about the federal government’s intentions, the chair of the expert panel, Mona Gupta, MD, told The Canadian Press that she did not think it was necessary to put off implementation because necessary safeguards were already in place.
Dr. Chaimowitz awaits the standards but is optimistic that for mental illness, “the process will be tightly controlled, closely monitored, and open to scrutiny,” he said.
Dr. Braswell is not convinced. The concern is that adding people with mental illness is “going to overload the capacity of the government to monitor this practice,” he said.
Is the United States next?
Although Canada and the United States share a border, it’s unlikely that U.S. states will allow aid in dying for nonterminal illness, much less for psychiatric conditions any time soon, said Dr. Braswell and others.
Ten states – California, Colorado, Hawaii, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, and Washington – have laws allowing assistance in dying, but for terminal illness only.
In 2016, the APA adopted the American Medical Association policy on medical euthanasia, stating, “that a psychiatrist should not prescribe or administer any intervention to a nonterminally ill person for the purpose of causing death.”
Dr. Brendel said the field is acutely aware that people with mental illness do suffer, but that more work needs to be done – and is being done – on “distinguishing wishes to hasten death or end one’s life from these historical or traditional notions that any premature death is a suicide.”
There is also increasing discussion within the medical community, not just psychiatry, about a physician’s duty to relieve suffering, said Dr. Wynia. “There’s debate basically about whether we stand for preserving life essentially at all costs and never being involved in the taking of life, or whether we stand for reduction of suffering and being the advocate for the patients that we serve,” he said.
“Those are both legitimate,” said Dr. Wynia, adding, “there are good reasons to want both of those to be true.”
“I suspect that 20 years from now we will still be having conversations about how physicians, how psychiatrists ought to participate in preserving life and in shepherding death,” said Dr. Brendel.
But to Dr. Gaind, the debate is not just esoteric, it’s a soon-to-be reality in Canada. “When we’re providing death to people who aren’t dying, to me that’s like providing what amounts to a wrongful death,” he said.
A version of this article originally appeared on Medscape.com.
Artificial intelligence applications in colonoscopy
Considerable advances in artificial intelligence (AI) and machine-learning (ML) methodologies have led to the emergence of promising tools in the field of gastrointestinal endoscopy. Computer vision is an application of AI/ML that has been successfully applied for the computer-aided detection (CADe) and computer-aided diagnosis (CADx) of colon polyps and numerous other conditions encountered during GI endoscopy. Outside of computer vision, a wide variety of other AI applications have been applied to gastroenterology, ranging from natural language processing (NLP) to optimize clinical documentation and endoscopy quality reporting to ML techniques that predict disease severity/treatment response and augment clinical decision-making.
In the United States, colonoscopy is the standard for colon cancer screening and prevention; however, precancerous polyps can be missed for various reasons, ranging from subtle surface appearance of the polyp or location behind a colonic fold to operator-dependent reasons such as inadequate mucosal inspection. Though clinical practice guidelines have set adenoma detection rate (ADR) thresholds at 20% for women and 30% for men, studies have shown a 4- to 10-fold variation in ADR among physicians in clinical practice settings,1 with an estimated adenoma miss rate (AMR) of 25% and a false-negative colonoscopy rate of 12%.2 Variability in adenoma detection affects the risk of interval colorectal cancer post colonoscopy.3,4
AI provides an opportunity for mitigating this risk. Advances in deep learning and computer vision have led to the development of CADe systems that automatically detect polyps in real time during colonoscopy, resulting in reduced adenoma miss rates (Table 1). In addition to polyp detection, deep-learning technologies are also being used in CADx systems for polyp diagnosis and characterization of malignancy risk. This could aid therapeutic decision-making: Unnecessary resection or histopathologic analysis could be obviated for benign hyperplastic polyps. On the other end of the polyp spectrum, an AI tool that could predict the presence or absence of submucosal invasion could be a powerful tool when evaluating early colon cancers for consideration of endoscopic submucosal dissection vs. surgery. Examples of CADe polyp detection and CADx polyp characterization are shown in Figure 1.
Other potential computer vision applications that may improve colonoscopy quality include tools that help measure adequacy of mucosal exposure, segmental inspection time, and a variety of other parameters associated with polyp detection performance. These are promising areas for future research. Beyond improving colonoscopy technique, natural language processing tools already are being used to optimize clinical documentation as well as extract information from colonoscopy and pathology reports that can facilitate reporting of colonoscopy quality metrics such as ADR, cecal intubation rate, withdrawal time, and bowel preparation adequacy. AI-powered analytics may help unlock large-scale reporting of colonoscopy quality metrics on a health-systems level5 or population-level,6 helping to ensure optimal performance and identifying avenues for colonoscopy quality improvement.
The majority of AI research in colonoscopy has focused on CADe for colon polyp detection and CADx for polyp diagnosis. Over the last few years, several randomized clinical trials – two in the United States – have shown that CADe significantly improves adenoma detection and reduces adenoma miss rates in comparison to standard colonoscopy. The existing data are summarized in Table 1, focusing on the two U.S. studies and an international meta-analysis.
In comparison, the data landscape for CADx is nascent and currently limited to several retrospective studies dating back to 2009 and a few prospective studies that have shown promising results.10,11 There is an expectation that integrated CADx also may support the adoption of “resect and discard” or “diagnose and leave” strategies for low-risk polyps. About two-thirds of polyps identified on average-risk screening colonoscopies are diminutive polyps (less than 5 mm in size), which rarely have advanced histologic features (about 0.5%) and are sometimes non-neoplastic (30%). Malignancy risk is even lower in the distal colon.12 As routine histopathologic assessment of such polyps is mostly of limited clinical utility and comes with added pathology costs, CADx technologies may offer a more cost-effective approach where polyps that are characterized in real-time as low-risk adenomas or non-neoplastic are “resected and discarded” or “left in” respectively. In 2011, prior to the development of current AI tools, the American Society for Gastrointestinal Endoscopy set performance thresholds for technologies supporting real-time endoscopic assessment of the histology of diminutive colorectal polyps. The ASGE recommended 90% histopathologic concordance for “resect and discard” tools and 90% negative predictive value for adenomatous histology for “diagnose and leave,” tools.13 Narrow-band imaging (NBI), for example, has been shown to meet these benchmarks14,15 with a modeling study suggesting that implementing “resect and discard” strategies with such tools could result in annual savings of $33 million without adversely affecting efficacy, although practical adoption has been limited.16 More recent work has directly explored the feasibility of leveraging CADx to support “leave-in-situ” and “resect-and-discard” strategies.17
Similarly, while CADe use in colonoscopy is associated with additional up-front costs, a modeling study suggests that its associated gains in ADR (as detailed in Table 1) make it a cost-saving strategy for colorectal cancer prevention in the long term.18 There is still uncertainty on whether the incremental CADe-associated gains in adenoma detection will necessarily translate to significant reductions in interval colorectal cancer risk, particularly for endoscopists who are already high-performing polyp detectors. A recent study suggests that, although higher ADRs were associated with lower rates of interval colorectal cancer, the gains in interval colorectal cancer risk reduction appeared to level off with ADRs above 35%-40% (this finding may be limited by statistical power).19 Further, most of the data from CADe trials suggest that gains in adenoma detection are not driven by increased detection of advanced lesions with high malignancy risk but by small polyps with long latency periods of about 5-10 years, which may not significantly alter interval cancer risk. It remains to be determined whether adoption of CADe will have an impact on hard outcomes, most importantly interval colorectal cancer risk, or merely result in increased resource utilization without moving the needle on colorectal cancer prevention. To answer this question, the OperA study – a large-scale randomized clinical trial of 200,000 patients across 18 centers from 13 countries – was launched in 2022. It will investigate the effect of colonoscopy with CADe on a number of critical measures, including long-term interval colon cancer risk.20
Despite commercial availability of regulatory-approved CADe systems and data supporting use for adenoma detection in colonoscopy, mainstream adoption in clinical practice has been sluggish. Physician survey studies have shown that, although there is considerable interest in integrating CADe into clinical practice, there are concerns about access, cost and reimbursement, integration into clinical work-flow, increased procedural times, over-reliance on AI, and algorithmic bias leading to errors.21,22 In addition, without mandatory requirements for ADR reporting or clinical practice guideline recommendations for CADe use, these systems may not be perceived as valuable or ready for prime time even though the evidence suggests otherwise.23,24 For CADe systems to see widespread adoption in clinical practice, it is important that future research studies rigorously investigate and characterize these potential barriers to better inform strategies to address AI hesitancy and implementation challenges. Such efforts can provide an integration framework for future AI applications in gastroenterology beyond colonoscopy, such as CADe of esophageal and gastric premalignant lesions in upper endoscopy, CADx for pancreatic cysts and liver lesions on imaging, NLP tools to optimizing efficient clinical documentation and reporting, and many others.
Dr. Uche-Anya is in the division of gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston. Dr. Berzin is with the Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. Dr. Berzin is a consultant for Wision AI, Medtronic, Magentiq Eye, RSIP Vision, and Docbot.
Corresponding Author: Eugenia Uche-Anya eucheanya@mgh.harvard.edu Twitter: @UcheAnyaMD @tberzin
References
1. Corley DA et al. Can we improve adenoma detection rates? A systematic review of intervention studies. Gastrointest Endosc. Sep 2011;74(3):656-65. doi: 10.1016/j.gie.2011.04.017.
2. Zhao S et al. Magnitude, risk factors, and factors associated with adenoma miss rate of tandem colonoscopy: A systematic review and meta-analysis. Gastroenterology. 05 2019;156(6):1661-74.e11. doi: 10.1053/j.gastro.2019.01.260.
3. Kaminski MF et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. May 13 2010;362(19):1795-803. doi: 10.1056/NEJMoa0907667.
4. Corley DA et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. Apr 03 2014;370(14):1298-306. doi: 10.1056/NEJMoa1309086.
5. Laique SN et al. Application of optical character recognition with natural language processing for large-scale quality metric data extraction in colonoscopy reports. Gastrointest Endosc. 03 2021;93(3):750-7. doi: 10.1016/j.gie.2020.08.038.
6. Tinmouth J et al. Validation of a natural language processing algorithm to identify adenomas and measure adenoma detection rates across a health system: a population-level study. Gastrointest Endosc. Jul 14 2022. doi: 10.1016/j.gie.2022.07.009.
7. Glissen Brown JR et al. Deep learning computer-aided polyp detection reduces adenoma miss rate: A United States multi-center randomized tandem colonoscopy study (CADeT-CS Trial). Clin Gastroenterol Hepatol. 07 2022;20(7):1499-1507.e4. doi: 10.1016/j.cgh.2021.09.009.
8. Wallace MB et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology. 07 2022;163(1):295-304.e5. doi: 10.1053/j.gastro.2022.03.007.
9. Hassan C et al. Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis. Gastrointest Endosc. 01 2021;93(1):77-85.e6. doi: 10.1016/j.gie.2020.06.059.
10. Glissen Brown JR and Berzin TM. Adoption of new technologies: Artificial intelligence. Gastrointest Endosc Clin N Am. Oct 2021;31(4):743-58. doi: 10.1016/j.giec.2021.05.010.
11. Larsen SLV and Mori Y. Artificial intelligence in colonoscopy: A review on the current status. DEN open. Apr 2022;2(1):e109. doi: 10.1002/deo2.109.
12. Gupta N et al. Prevalence of advanced histological features in diminutive and small colon polyps. Gastrointest Endosc. May 2012;75(5):1022-30. doi: 10.1016/j.gie.2012.01.020.
13. Rex DK et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2011;73(3):419-22. doi: 10.1016/j.gie.2011.01.023.
14. Abu Dayyeh BK et al. ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2015;81(3):502.e1-16. doi: 10.1016/j.gie.2014.12.022.
15. Mori Y et al. Real-time use of artificial intelligence in identification of diminutive polyps during colonoscopy: A prospective study. Ann Intern Med. Sep 18 2018;169(6):357-66. doi: 10.7326/M18-0249.
16. Hassan C et al.. A resect and discard strategy would improve cost-effectiveness of colorectal cancer screening. Clin Gastroenterol Hepatol. Oct 2010;8(10):865-9, 869.e1-3. doi: 10.1016/j.cgh.2010.05.018.
17. Hassan C et al. Artificial intelligence allows leaving-in-situ colorectal polyps. Clin Gastroenterol Hepatol. Nov 2022;20(11):2505-13.e4. doi: 10.1016/j.cgh.2022.04.045.
18. Areia M et al. Cost-effectiveness of artificial intelligence for screening colonoscopy: a modelling study. Lancet Digit Health. 06 2022;4(6):e436-44. doi: 10.1016/S2589-7500(22)00042-5.
19. Schottinger JE et al. Association of physician adenoma detection rates with postcolonoscopy colorectal cancer. JAMA. 2022 Jun 7;327(21):2114-22. doi: 10.1001/jama.2022.6644.
20. Oslo Uo. Optimising colorectal cancer prevention through personalised treatment with artificial intelligence. 2022.
21. Wadhwa V et al. Physician sentiment toward artificial intelligence (AI) in colonoscopic practice: a survey of US gastroenterologists. Endosc Int Open. Oct 2020;8(10):E1379-84. doi: 10.1055/a-1223-1926.
22. Kader R et al. Survey on the perceptions of UK gastroenterologists and endoscopists to artificial intelligence. Frontline Gastroenterol. 2022;13(5):423-9. doi: 10.1136/flgastro-2021-101994.
23. Rex DKet al. Artificial intelligence improves detection at colonoscopy: Why aren’t we all already using it? Gastroenterology. 07 2022;163(1):35-7. doi: 10.1053/j.gastro.2022.04.042.
24. Ahmad OF et al. Establishing key research questions for the implementation of artificial intelligence in colonoscopy: A modified Delphi method. Endoscopy. 09 2021;53(9):893-901. doi: 10.1055/a-1306-7590
Considerable advances in artificial intelligence (AI) and machine-learning (ML) methodologies have led to the emergence of promising tools in the field of gastrointestinal endoscopy. Computer vision is an application of AI/ML that has been successfully applied for the computer-aided detection (CADe) and computer-aided diagnosis (CADx) of colon polyps and numerous other conditions encountered during GI endoscopy. Outside of computer vision, a wide variety of other AI applications have been applied to gastroenterology, ranging from natural language processing (NLP) to optimize clinical documentation and endoscopy quality reporting to ML techniques that predict disease severity/treatment response and augment clinical decision-making.
In the United States, colonoscopy is the standard for colon cancer screening and prevention; however, precancerous polyps can be missed for various reasons, ranging from subtle surface appearance of the polyp or location behind a colonic fold to operator-dependent reasons such as inadequate mucosal inspection. Though clinical practice guidelines have set adenoma detection rate (ADR) thresholds at 20% for women and 30% for men, studies have shown a 4- to 10-fold variation in ADR among physicians in clinical practice settings,1 with an estimated adenoma miss rate (AMR) of 25% and a false-negative colonoscopy rate of 12%.2 Variability in adenoma detection affects the risk of interval colorectal cancer post colonoscopy.3,4
AI provides an opportunity for mitigating this risk. Advances in deep learning and computer vision have led to the development of CADe systems that automatically detect polyps in real time during colonoscopy, resulting in reduced adenoma miss rates (Table 1). In addition to polyp detection, deep-learning technologies are also being used in CADx systems for polyp diagnosis and characterization of malignancy risk. This could aid therapeutic decision-making: Unnecessary resection or histopathologic analysis could be obviated for benign hyperplastic polyps. On the other end of the polyp spectrum, an AI tool that could predict the presence or absence of submucosal invasion could be a powerful tool when evaluating early colon cancers for consideration of endoscopic submucosal dissection vs. surgery. Examples of CADe polyp detection and CADx polyp characterization are shown in Figure 1.
Other potential computer vision applications that may improve colonoscopy quality include tools that help measure adequacy of mucosal exposure, segmental inspection time, and a variety of other parameters associated with polyp detection performance. These are promising areas for future research. Beyond improving colonoscopy technique, natural language processing tools already are being used to optimize clinical documentation as well as extract information from colonoscopy and pathology reports that can facilitate reporting of colonoscopy quality metrics such as ADR, cecal intubation rate, withdrawal time, and bowel preparation adequacy. AI-powered analytics may help unlock large-scale reporting of colonoscopy quality metrics on a health-systems level5 or population-level,6 helping to ensure optimal performance and identifying avenues for colonoscopy quality improvement.
The majority of AI research in colonoscopy has focused on CADe for colon polyp detection and CADx for polyp diagnosis. Over the last few years, several randomized clinical trials – two in the United States – have shown that CADe significantly improves adenoma detection and reduces adenoma miss rates in comparison to standard colonoscopy. The existing data are summarized in Table 1, focusing on the two U.S. studies and an international meta-analysis.
In comparison, the data landscape for CADx is nascent and currently limited to several retrospective studies dating back to 2009 and a few prospective studies that have shown promising results.10,11 There is an expectation that integrated CADx also may support the adoption of “resect and discard” or “diagnose and leave” strategies for low-risk polyps. About two-thirds of polyps identified on average-risk screening colonoscopies are diminutive polyps (less than 5 mm in size), which rarely have advanced histologic features (about 0.5%) and are sometimes non-neoplastic (30%). Malignancy risk is even lower in the distal colon.12 As routine histopathologic assessment of such polyps is mostly of limited clinical utility and comes with added pathology costs, CADx technologies may offer a more cost-effective approach where polyps that are characterized in real-time as low-risk adenomas or non-neoplastic are “resected and discarded” or “left in” respectively. In 2011, prior to the development of current AI tools, the American Society for Gastrointestinal Endoscopy set performance thresholds for technologies supporting real-time endoscopic assessment of the histology of diminutive colorectal polyps. The ASGE recommended 90% histopathologic concordance for “resect and discard” tools and 90% negative predictive value for adenomatous histology for “diagnose and leave,” tools.13 Narrow-band imaging (NBI), for example, has been shown to meet these benchmarks14,15 with a modeling study suggesting that implementing “resect and discard” strategies with such tools could result in annual savings of $33 million without adversely affecting efficacy, although practical adoption has been limited.16 More recent work has directly explored the feasibility of leveraging CADx to support “leave-in-situ” and “resect-and-discard” strategies.17
Similarly, while CADe use in colonoscopy is associated with additional up-front costs, a modeling study suggests that its associated gains in ADR (as detailed in Table 1) make it a cost-saving strategy for colorectal cancer prevention in the long term.18 There is still uncertainty on whether the incremental CADe-associated gains in adenoma detection will necessarily translate to significant reductions in interval colorectal cancer risk, particularly for endoscopists who are already high-performing polyp detectors. A recent study suggests that, although higher ADRs were associated with lower rates of interval colorectal cancer, the gains in interval colorectal cancer risk reduction appeared to level off with ADRs above 35%-40% (this finding may be limited by statistical power).19 Further, most of the data from CADe trials suggest that gains in adenoma detection are not driven by increased detection of advanced lesions with high malignancy risk but by small polyps with long latency periods of about 5-10 years, which may not significantly alter interval cancer risk. It remains to be determined whether adoption of CADe will have an impact on hard outcomes, most importantly interval colorectal cancer risk, or merely result in increased resource utilization without moving the needle on colorectal cancer prevention. To answer this question, the OperA study – a large-scale randomized clinical trial of 200,000 patients across 18 centers from 13 countries – was launched in 2022. It will investigate the effect of colonoscopy with CADe on a number of critical measures, including long-term interval colon cancer risk.20
Despite commercial availability of regulatory-approved CADe systems and data supporting use for adenoma detection in colonoscopy, mainstream adoption in clinical practice has been sluggish. Physician survey studies have shown that, although there is considerable interest in integrating CADe into clinical practice, there are concerns about access, cost and reimbursement, integration into clinical work-flow, increased procedural times, over-reliance on AI, and algorithmic bias leading to errors.21,22 In addition, without mandatory requirements for ADR reporting or clinical practice guideline recommendations for CADe use, these systems may not be perceived as valuable or ready for prime time even though the evidence suggests otherwise.23,24 For CADe systems to see widespread adoption in clinical practice, it is important that future research studies rigorously investigate and characterize these potential barriers to better inform strategies to address AI hesitancy and implementation challenges. Such efforts can provide an integration framework for future AI applications in gastroenterology beyond colonoscopy, such as CADe of esophageal and gastric premalignant lesions in upper endoscopy, CADx for pancreatic cysts and liver lesions on imaging, NLP tools to optimizing efficient clinical documentation and reporting, and many others.
Dr. Uche-Anya is in the division of gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston. Dr. Berzin is with the Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. Dr. Berzin is a consultant for Wision AI, Medtronic, Magentiq Eye, RSIP Vision, and Docbot.
Corresponding Author: Eugenia Uche-Anya eucheanya@mgh.harvard.edu Twitter: @UcheAnyaMD @tberzin
References
1. Corley DA et al. Can we improve adenoma detection rates? A systematic review of intervention studies. Gastrointest Endosc. Sep 2011;74(3):656-65. doi: 10.1016/j.gie.2011.04.017.
2. Zhao S et al. Magnitude, risk factors, and factors associated with adenoma miss rate of tandem colonoscopy: A systematic review and meta-analysis. Gastroenterology. 05 2019;156(6):1661-74.e11. doi: 10.1053/j.gastro.2019.01.260.
3. Kaminski MF et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. May 13 2010;362(19):1795-803. doi: 10.1056/NEJMoa0907667.
4. Corley DA et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. Apr 03 2014;370(14):1298-306. doi: 10.1056/NEJMoa1309086.
5. Laique SN et al. Application of optical character recognition with natural language processing for large-scale quality metric data extraction in colonoscopy reports. Gastrointest Endosc. 03 2021;93(3):750-7. doi: 10.1016/j.gie.2020.08.038.
6. Tinmouth J et al. Validation of a natural language processing algorithm to identify adenomas and measure adenoma detection rates across a health system: a population-level study. Gastrointest Endosc. Jul 14 2022. doi: 10.1016/j.gie.2022.07.009.
7. Glissen Brown JR et al. Deep learning computer-aided polyp detection reduces adenoma miss rate: A United States multi-center randomized tandem colonoscopy study (CADeT-CS Trial). Clin Gastroenterol Hepatol. 07 2022;20(7):1499-1507.e4. doi: 10.1016/j.cgh.2021.09.009.
8. Wallace MB et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology. 07 2022;163(1):295-304.e5. doi: 10.1053/j.gastro.2022.03.007.
9. Hassan C et al. Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis. Gastrointest Endosc. 01 2021;93(1):77-85.e6. doi: 10.1016/j.gie.2020.06.059.
10. Glissen Brown JR and Berzin TM. Adoption of new technologies: Artificial intelligence. Gastrointest Endosc Clin N Am. Oct 2021;31(4):743-58. doi: 10.1016/j.giec.2021.05.010.
11. Larsen SLV and Mori Y. Artificial intelligence in colonoscopy: A review on the current status. DEN open. Apr 2022;2(1):e109. doi: 10.1002/deo2.109.
12. Gupta N et al. Prevalence of advanced histological features in diminutive and small colon polyps. Gastrointest Endosc. May 2012;75(5):1022-30. doi: 10.1016/j.gie.2012.01.020.
13. Rex DK et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2011;73(3):419-22. doi: 10.1016/j.gie.2011.01.023.
14. Abu Dayyeh BK et al. ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2015;81(3):502.e1-16. doi: 10.1016/j.gie.2014.12.022.
15. Mori Y et al. Real-time use of artificial intelligence in identification of diminutive polyps during colonoscopy: A prospective study. Ann Intern Med. Sep 18 2018;169(6):357-66. doi: 10.7326/M18-0249.
16. Hassan C et al.. A resect and discard strategy would improve cost-effectiveness of colorectal cancer screening. Clin Gastroenterol Hepatol. Oct 2010;8(10):865-9, 869.e1-3. doi: 10.1016/j.cgh.2010.05.018.
17. Hassan C et al. Artificial intelligence allows leaving-in-situ colorectal polyps. Clin Gastroenterol Hepatol. Nov 2022;20(11):2505-13.e4. doi: 10.1016/j.cgh.2022.04.045.
18. Areia M et al. Cost-effectiveness of artificial intelligence for screening colonoscopy: a modelling study. Lancet Digit Health. 06 2022;4(6):e436-44. doi: 10.1016/S2589-7500(22)00042-5.
19. Schottinger JE et al. Association of physician adenoma detection rates with postcolonoscopy colorectal cancer. JAMA. 2022 Jun 7;327(21):2114-22. doi: 10.1001/jama.2022.6644.
20. Oslo Uo. Optimising colorectal cancer prevention through personalised treatment with artificial intelligence. 2022.
21. Wadhwa V et al. Physician sentiment toward artificial intelligence (AI) in colonoscopic practice: a survey of US gastroenterologists. Endosc Int Open. Oct 2020;8(10):E1379-84. doi: 10.1055/a-1223-1926.
22. Kader R et al. Survey on the perceptions of UK gastroenterologists and endoscopists to artificial intelligence. Frontline Gastroenterol. 2022;13(5):423-9. doi: 10.1136/flgastro-2021-101994.
23. Rex DKet al. Artificial intelligence improves detection at colonoscopy: Why aren’t we all already using it? Gastroenterology. 07 2022;163(1):35-7. doi: 10.1053/j.gastro.2022.04.042.
24. Ahmad OF et al. Establishing key research questions for the implementation of artificial intelligence in colonoscopy: A modified Delphi method. Endoscopy. 09 2021;53(9):893-901. doi: 10.1055/a-1306-7590
Considerable advances in artificial intelligence (AI) and machine-learning (ML) methodologies have led to the emergence of promising tools in the field of gastrointestinal endoscopy. Computer vision is an application of AI/ML that has been successfully applied for the computer-aided detection (CADe) and computer-aided diagnosis (CADx) of colon polyps and numerous other conditions encountered during GI endoscopy. Outside of computer vision, a wide variety of other AI applications have been applied to gastroenterology, ranging from natural language processing (NLP) to optimize clinical documentation and endoscopy quality reporting to ML techniques that predict disease severity/treatment response and augment clinical decision-making.
In the United States, colonoscopy is the standard for colon cancer screening and prevention; however, precancerous polyps can be missed for various reasons, ranging from subtle surface appearance of the polyp or location behind a colonic fold to operator-dependent reasons such as inadequate mucosal inspection. Though clinical practice guidelines have set adenoma detection rate (ADR) thresholds at 20% for women and 30% for men, studies have shown a 4- to 10-fold variation in ADR among physicians in clinical practice settings,1 with an estimated adenoma miss rate (AMR) of 25% and a false-negative colonoscopy rate of 12%.2 Variability in adenoma detection affects the risk of interval colorectal cancer post colonoscopy.3,4
AI provides an opportunity for mitigating this risk. Advances in deep learning and computer vision have led to the development of CADe systems that automatically detect polyps in real time during colonoscopy, resulting in reduced adenoma miss rates (Table 1). In addition to polyp detection, deep-learning technologies are also being used in CADx systems for polyp diagnosis and characterization of malignancy risk. This could aid therapeutic decision-making: Unnecessary resection or histopathologic analysis could be obviated for benign hyperplastic polyps. On the other end of the polyp spectrum, an AI tool that could predict the presence or absence of submucosal invasion could be a powerful tool when evaluating early colon cancers for consideration of endoscopic submucosal dissection vs. surgery. Examples of CADe polyp detection and CADx polyp characterization are shown in Figure 1.
Other potential computer vision applications that may improve colonoscopy quality include tools that help measure adequacy of mucosal exposure, segmental inspection time, and a variety of other parameters associated with polyp detection performance. These are promising areas for future research. Beyond improving colonoscopy technique, natural language processing tools already are being used to optimize clinical documentation as well as extract information from colonoscopy and pathology reports that can facilitate reporting of colonoscopy quality metrics such as ADR, cecal intubation rate, withdrawal time, and bowel preparation adequacy. AI-powered analytics may help unlock large-scale reporting of colonoscopy quality metrics on a health-systems level5 or population-level,6 helping to ensure optimal performance and identifying avenues for colonoscopy quality improvement.
The majority of AI research in colonoscopy has focused on CADe for colon polyp detection and CADx for polyp diagnosis. Over the last few years, several randomized clinical trials – two in the United States – have shown that CADe significantly improves adenoma detection and reduces adenoma miss rates in comparison to standard colonoscopy. The existing data are summarized in Table 1, focusing on the two U.S. studies and an international meta-analysis.
In comparison, the data landscape for CADx is nascent and currently limited to several retrospective studies dating back to 2009 and a few prospective studies that have shown promising results.10,11 There is an expectation that integrated CADx also may support the adoption of “resect and discard” or “diagnose and leave” strategies for low-risk polyps. About two-thirds of polyps identified on average-risk screening colonoscopies are diminutive polyps (less than 5 mm in size), which rarely have advanced histologic features (about 0.5%) and are sometimes non-neoplastic (30%). Malignancy risk is even lower in the distal colon.12 As routine histopathologic assessment of such polyps is mostly of limited clinical utility and comes with added pathology costs, CADx technologies may offer a more cost-effective approach where polyps that are characterized in real-time as low-risk adenomas or non-neoplastic are “resected and discarded” or “left in” respectively. In 2011, prior to the development of current AI tools, the American Society for Gastrointestinal Endoscopy set performance thresholds for technologies supporting real-time endoscopic assessment of the histology of diminutive colorectal polyps. The ASGE recommended 90% histopathologic concordance for “resect and discard” tools and 90% negative predictive value for adenomatous histology for “diagnose and leave,” tools.13 Narrow-band imaging (NBI), for example, has been shown to meet these benchmarks14,15 with a modeling study suggesting that implementing “resect and discard” strategies with such tools could result in annual savings of $33 million without adversely affecting efficacy, although practical adoption has been limited.16 More recent work has directly explored the feasibility of leveraging CADx to support “leave-in-situ” and “resect-and-discard” strategies.17
Similarly, while CADe use in colonoscopy is associated with additional up-front costs, a modeling study suggests that its associated gains in ADR (as detailed in Table 1) make it a cost-saving strategy for colorectal cancer prevention in the long term.18 There is still uncertainty on whether the incremental CADe-associated gains in adenoma detection will necessarily translate to significant reductions in interval colorectal cancer risk, particularly for endoscopists who are already high-performing polyp detectors. A recent study suggests that, although higher ADRs were associated with lower rates of interval colorectal cancer, the gains in interval colorectal cancer risk reduction appeared to level off with ADRs above 35%-40% (this finding may be limited by statistical power).19 Further, most of the data from CADe trials suggest that gains in adenoma detection are not driven by increased detection of advanced lesions with high malignancy risk but by small polyps with long latency periods of about 5-10 years, which may not significantly alter interval cancer risk. It remains to be determined whether adoption of CADe will have an impact on hard outcomes, most importantly interval colorectal cancer risk, or merely result in increased resource utilization without moving the needle on colorectal cancer prevention. To answer this question, the OperA study – a large-scale randomized clinical trial of 200,000 patients across 18 centers from 13 countries – was launched in 2022. It will investigate the effect of colonoscopy with CADe on a number of critical measures, including long-term interval colon cancer risk.20
Despite commercial availability of regulatory-approved CADe systems and data supporting use for adenoma detection in colonoscopy, mainstream adoption in clinical practice has been sluggish. Physician survey studies have shown that, although there is considerable interest in integrating CADe into clinical practice, there are concerns about access, cost and reimbursement, integration into clinical work-flow, increased procedural times, over-reliance on AI, and algorithmic bias leading to errors.21,22 In addition, without mandatory requirements for ADR reporting or clinical practice guideline recommendations for CADe use, these systems may not be perceived as valuable or ready for prime time even though the evidence suggests otherwise.23,24 For CADe systems to see widespread adoption in clinical practice, it is important that future research studies rigorously investigate and characterize these potential barriers to better inform strategies to address AI hesitancy and implementation challenges. Such efforts can provide an integration framework for future AI applications in gastroenterology beyond colonoscopy, such as CADe of esophageal and gastric premalignant lesions in upper endoscopy, CADx for pancreatic cysts and liver lesions on imaging, NLP tools to optimizing efficient clinical documentation and reporting, and many others.
Dr. Uche-Anya is in the division of gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston. Dr. Berzin is with the Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. Dr. Berzin is a consultant for Wision AI, Medtronic, Magentiq Eye, RSIP Vision, and Docbot.
Corresponding Author: Eugenia Uche-Anya eucheanya@mgh.harvard.edu Twitter: @UcheAnyaMD @tberzin
References
1. Corley DA et al. Can we improve adenoma detection rates? A systematic review of intervention studies. Gastrointest Endosc. Sep 2011;74(3):656-65. doi: 10.1016/j.gie.2011.04.017.
2. Zhao S et al. Magnitude, risk factors, and factors associated with adenoma miss rate of tandem colonoscopy: A systematic review and meta-analysis. Gastroenterology. 05 2019;156(6):1661-74.e11. doi: 10.1053/j.gastro.2019.01.260.
3. Kaminski MF et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. May 13 2010;362(19):1795-803. doi: 10.1056/NEJMoa0907667.
4. Corley DA et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. Apr 03 2014;370(14):1298-306. doi: 10.1056/NEJMoa1309086.
5. Laique SN et al. Application of optical character recognition with natural language processing for large-scale quality metric data extraction in colonoscopy reports. Gastrointest Endosc. 03 2021;93(3):750-7. doi: 10.1016/j.gie.2020.08.038.
6. Tinmouth J et al. Validation of a natural language processing algorithm to identify adenomas and measure adenoma detection rates across a health system: a population-level study. Gastrointest Endosc. Jul 14 2022. doi: 10.1016/j.gie.2022.07.009.
7. Glissen Brown JR et al. Deep learning computer-aided polyp detection reduces adenoma miss rate: A United States multi-center randomized tandem colonoscopy study (CADeT-CS Trial). Clin Gastroenterol Hepatol. 07 2022;20(7):1499-1507.e4. doi: 10.1016/j.cgh.2021.09.009.
8. Wallace MB et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology. 07 2022;163(1):295-304.e5. doi: 10.1053/j.gastro.2022.03.007.
9. Hassan C et al. Performance of artificial intelligence in colonoscopy for adenoma and polyp detection: a systematic review and meta-analysis. Gastrointest Endosc. 01 2021;93(1):77-85.e6. doi: 10.1016/j.gie.2020.06.059.
10. Glissen Brown JR and Berzin TM. Adoption of new technologies: Artificial intelligence. Gastrointest Endosc Clin N Am. Oct 2021;31(4):743-58. doi: 10.1016/j.giec.2021.05.010.
11. Larsen SLV and Mori Y. Artificial intelligence in colonoscopy: A review on the current status. DEN open. Apr 2022;2(1):e109. doi: 10.1002/deo2.109.
12. Gupta N et al. Prevalence of advanced histological features in diminutive and small colon polyps. Gastrointest Endosc. May 2012;75(5):1022-30. doi: 10.1016/j.gie.2012.01.020.
13. Rex DK et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2011;73(3):419-22. doi: 10.1016/j.gie.2011.01.023.
14. Abu Dayyeh BK et al. ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. Mar 2015;81(3):502.e1-16. doi: 10.1016/j.gie.2014.12.022.
15. Mori Y et al. Real-time use of artificial intelligence in identification of diminutive polyps during colonoscopy: A prospective study. Ann Intern Med. Sep 18 2018;169(6):357-66. doi: 10.7326/M18-0249.
16. Hassan C et al.. A resect and discard strategy would improve cost-effectiveness of colorectal cancer screening. Clin Gastroenterol Hepatol. Oct 2010;8(10):865-9, 869.e1-3. doi: 10.1016/j.cgh.2010.05.018.
17. Hassan C et al. Artificial intelligence allows leaving-in-situ colorectal polyps. Clin Gastroenterol Hepatol. Nov 2022;20(11):2505-13.e4. doi: 10.1016/j.cgh.2022.04.045.
18. Areia M et al. Cost-effectiveness of artificial intelligence for screening colonoscopy: a modelling study. Lancet Digit Health. 06 2022;4(6):e436-44. doi: 10.1016/S2589-7500(22)00042-5.
19. Schottinger JE et al. Association of physician adenoma detection rates with postcolonoscopy colorectal cancer. JAMA. 2022 Jun 7;327(21):2114-22. doi: 10.1001/jama.2022.6644.
20. Oslo Uo. Optimising colorectal cancer prevention through personalised treatment with artificial intelligence. 2022.
21. Wadhwa V et al. Physician sentiment toward artificial intelligence (AI) in colonoscopic practice: a survey of US gastroenterologists. Endosc Int Open. Oct 2020;8(10):E1379-84. doi: 10.1055/a-1223-1926.
22. Kader R et al. Survey on the perceptions of UK gastroenterologists and endoscopists to artificial intelligence. Frontline Gastroenterol. 2022;13(5):423-9. doi: 10.1136/flgastro-2021-101994.
23. Rex DKet al. Artificial intelligence improves detection at colonoscopy: Why aren’t we all already using it? Gastroenterology. 07 2022;163(1):35-7. doi: 10.1053/j.gastro.2022.04.042.
24. Ahmad OF et al. Establishing key research questions for the implementation of artificial intelligence in colonoscopy: A modified Delphi method. Endoscopy. 09 2021;53(9):893-901. doi: 10.1055/a-1306-7590
Mastocytosis: Rare, underdiagnosed, potentially fatal
Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.
More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.
Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.
“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”
Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).
In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.
ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.
The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”
Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.
“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.
A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.
The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.
Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.
Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”
Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.
Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.
As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.
How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.
This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.
Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).
Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.
As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.
“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.
“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.
Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.
Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.
More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.
Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.
“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”
Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).
In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.
ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.
The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”
Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.
“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.
A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.
The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.
Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.
Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”
Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.
Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.
As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.
How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.
This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.
Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).
Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.
As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.
“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.
“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.
Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.
Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.
More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.
Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.
“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”
Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).
In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.
ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.
The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”
Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.
“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.
A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.
The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.
Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.
Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”
Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.
Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.
As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.
How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.
This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.
Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).
Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.
As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.
“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.
“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.
Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.