User login
DIY Brain Stimulation Is Growing in Popularity, but Is It Safe, Effective?
As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.
However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.
This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.
So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
What the Research Shows
Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.
“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.
Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.
“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.
tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.
As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.
Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.
On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.
In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.
Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
On-Demand Brain Stim
As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.
Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.
So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.
In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.
Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.
Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”
Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
A Quick Fix for a Broken System?
Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.
“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.
There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.
“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.
Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”
“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.
As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.
He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.
In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.
“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.
“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
Ethical Considerations
Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.
“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.
In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.
On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.
The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.
“This raises concerns because the way you use the device is important,” he said.
Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.
This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.
“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.
Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.
Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.
Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
A version of this article first appeared on Medscape.com.
As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.
However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.
This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.
So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
What the Research Shows
Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.
“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.
Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.
“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.
tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.
As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.
Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.
On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.
In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.
Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
On-Demand Brain Stim
As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.
Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.
So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.
In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.
Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.
Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”
Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
A Quick Fix for a Broken System?
Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.
“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.
There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.
“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.
Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”
“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.
As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.
He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.
In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.
“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.
“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
Ethical Considerations
Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.
“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.
In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.
On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.
The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.
“This raises concerns because the way you use the device is important,” he said.
Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.
This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.
“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.
Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.
Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.
Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
A version of this article first appeared on Medscape.com.
As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.
However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.
This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.
So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
What the Research Shows
Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.
“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.
Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.
“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.
tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.
As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.
Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.
On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.
In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.
Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
On-Demand Brain Stim
As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.
Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.
So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.
In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.
Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.
Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”
Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
A Quick Fix for a Broken System?
Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.
“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.
There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.
“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.
Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”
“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.
As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.
He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.
In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.
“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.
“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
Ethical Considerations
Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.
“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.
In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.
On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.
The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.
“This raises concerns because the way you use the device is important,” he said.
Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.
This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.
“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.
Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.
Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.
Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
A version of this article first appeared on Medscape.com.
Physician Empathy Mitigates Patients’ Chronic Pain
Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.
Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
Estimating Empathy
Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.
Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.
The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
Doctor-Patient Relationship
Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.
Treating Chronic Pain
Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).
Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:
- The CARE score was inversely associated with pain intensity (P < .001).
- Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
- The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
- The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
- The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.
Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.
Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
Estimating Empathy
Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.
Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.
The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
Doctor-Patient Relationship
Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.
Treating Chronic Pain
Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).
Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:
- The CARE score was inversely associated with pain intensity (P < .001).
- Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
- The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
- The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
- The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.
Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.
Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
Estimating Empathy
Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.
Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.
The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
Doctor-Patient Relationship
Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.
Treating Chronic Pain
Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).
Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:
- The CARE score was inversely associated with pain intensity (P < .001).
- Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
- The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
- The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
- The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.
Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
GI Docs Will Need to Forge a ‘Human-Computer Cooperative’
Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.
Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
How did you first become involved in studying AI applications for GI conditions?
My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.
I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?
I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.
I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
How did your early research go about trying to solve that problem?
My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.
I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.
Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
How did you convert the promise of CNN into tangible results?
The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.
In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.
Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.
Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.
To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.
What took us 3 years in 2016 would take about 3 weeks today.
You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?
We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.
The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.
For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.
Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.
Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.
Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
Were there any surprises in your work?
I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.
AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.
With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?
Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.
We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.
The inevitability of AI-powered transformations in gastroenterology care became apparent.
Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.
AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
What does adaptation look like for gastroenterologists over the next handful of years?
Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.
Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.
That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.
A version of this article appeared on Medscape.com.
Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.
Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
How did you first become involved in studying AI applications for GI conditions?
My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.
I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?
I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.
I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
How did your early research go about trying to solve that problem?
My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.
I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.
Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
How did you convert the promise of CNN into tangible results?
The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.
In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.
Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.
Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.
To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.
What took us 3 years in 2016 would take about 3 weeks today.
You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?
We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.
The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.
For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.
Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.
Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.
Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
Were there any surprises in your work?
I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.
AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.
With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?
Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.
We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.
The inevitability of AI-powered transformations in gastroenterology care became apparent.
Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.
AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
What does adaptation look like for gastroenterologists over the next handful of years?
Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.
Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.
That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.
A version of this article appeared on Medscape.com.
Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.
Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
How did you first become involved in studying AI applications for GI conditions?
My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.
I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?
I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.
I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
How did your early research go about trying to solve that problem?
My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.
I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.
Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
How did you convert the promise of CNN into tangible results?
The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.
In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.
Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.
Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.
To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.
What took us 3 years in 2016 would take about 3 weeks today.
You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?
We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.
The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.
For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.
Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.
Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.
Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
Were there any surprises in your work?
I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.
AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.
With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?
Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.
We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.
The inevitability of AI-powered transformations in gastroenterology care became apparent.
Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.
AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
What does adaptation look like for gastroenterologists over the next handful of years?
Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.
Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.
That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.
A version of this article appeared on Medscape.com.
Many Hurdles Exist to Treating Lung Cancer With CAR T Cells
These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.
“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.
He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.
Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.
Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.
He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”
A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
Identifying the Right Target
“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.
“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.
“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.
“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”
To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”
Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”
“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
A Question of Time
Another aspect of CAR T-cell therapy that is proving difficult is its delivery.
Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.
This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.
There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.
“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
Life-Threatening Toxicities
To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.
This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”
“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.
Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.
“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.
Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”
Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.
“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
‘At What Cost’ to Patients?
The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.
“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.
Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”
This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.
Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.
This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”
For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.
“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”
“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.
No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.
These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.
“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.
He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.
Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.
Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.
He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”
A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
Identifying the Right Target
“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.
“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.
“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.
“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”
To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”
Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”
“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
A Question of Time
Another aspect of CAR T-cell therapy that is proving difficult is its delivery.
Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.
This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.
There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.
“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
Life-Threatening Toxicities
To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.
This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”
“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.
Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.
“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.
Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”
Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.
“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
‘At What Cost’ to Patients?
The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.
“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.
Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”
This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.
Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.
This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”
For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.
“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”
“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.
No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.
These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.
“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.
He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.
Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.
Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.
He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”
A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
Identifying the Right Target
“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.
“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.
“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.
“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”
To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”
Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”
“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
A Question of Time
Another aspect of CAR T-cell therapy that is proving difficult is its delivery.
Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.
This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.
There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.
“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
Life-Threatening Toxicities
To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.
This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”
“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.
Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.
“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.
Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”
Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.
“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
‘At What Cost’ to Patients?
The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.
“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.
Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”
This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.
Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.
This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”
For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.
“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”
“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.
No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.
FROM WCLC 2024
How to Treat Cancer While Preserving Fertility
Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.
Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
Therapy Selection
The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. “Preserving fertility is also an aim of cancer therapy,” he said.
Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.
Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”
Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
Chemotherapies and Immunotherapies
Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.
Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.
These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.
Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.
In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.
Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”
In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.
In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
Adjusting the Regimen
In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.
By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.
During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.
Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.
FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.
Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
More Data Needed
The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.
For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.
The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.
Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
Therapy Selection
The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. “Preserving fertility is also an aim of cancer therapy,” he said.
Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.
Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”
Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
Chemotherapies and Immunotherapies
Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.
Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.
These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.
Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.
In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.
Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”
In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.
In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
Adjusting the Regimen
In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.
By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.
During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.
Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.
FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.
Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
More Data Needed
The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.
For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.
The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.
Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
Therapy Selection
The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. “Preserving fertility is also an aim of cancer therapy,” he said.
Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.
Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”
Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
Chemotherapies and Immunotherapies
Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.
Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.
These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.
Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.
In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.
Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”
In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.
In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
Adjusting the Regimen
In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.
By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.
During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.
Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.
FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.
Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
More Data Needed
The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.
For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.
The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The Biology of ‘Precancer’: Stopping Cancer Before It Starts
Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.
But they have long wondered why.
“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”
Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.
DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.
“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.
The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.
While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.
“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
‘We’re Basically Unearthing the Dark Matter of the Human Genome’
Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.
In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.
“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.
Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).
They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.
“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”
These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.
In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.
But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.
This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.
And that “critical juncture” may very well be the optimal time for intervention.
The Precancer Push
Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”
Many labs are trying to understand the biology of precancer and exploring possible vaccines.
The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.
Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.
At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.
Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.
In the years and decades to come, all of this could lead to a new era in cancer treatment.
“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”
A version of this article first appeared on Medscape.com.
Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.
But they have long wondered why.
“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”
Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.
DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.
“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.
The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.
While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.
“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
‘We’re Basically Unearthing the Dark Matter of the Human Genome’
Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.
In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.
“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.
Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).
They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.
“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”
These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.
In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.
But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.
This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.
And that “critical juncture” may very well be the optimal time for intervention.
The Precancer Push
Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”
Many labs are trying to understand the biology of precancer and exploring possible vaccines.
The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.
Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.
At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.
Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.
In the years and decades to come, all of this could lead to a new era in cancer treatment.
“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”
A version of this article first appeared on Medscape.com.
Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.
But they have long wondered why.
“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”
Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.
DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.
“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.
The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.
While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.
“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
‘We’re Basically Unearthing the Dark Matter of the Human Genome’
Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.
In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.
“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.
Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).
They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.
“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”
These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.
In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.
But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.
This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.
And that “critical juncture” may very well be the optimal time for intervention.
The Precancer Push
Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”
Many labs are trying to understand the biology of precancer and exploring possible vaccines.
The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.
Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.
At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.
Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.
In the years and decades to come, all of this could lead to a new era in cancer treatment.
“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”
A version of this article first appeared on Medscape.com.
Ghost Fat: The Unseen Consequences of Weight Loss
Many people who lose weight, whether through diet and lifestyle changes, medication, or bariatric surgery, recognize their body has changed. While they also experience improvements in quality of life and psychosocial areas, that’s not true for everyone. Some patients don’t “see” they’ve lost weight — a phenomenon referred to as “phantom fat,” “ghost fat,” or “vestigial body image.”
“Most people are happy with their appearance, or at least their body shape, after weight loss — although some are unhappy with the loose, sagging skin that can follow weight loss and seek plastic surgery to remedy that,” David B. Sarwer, PhD, director of the Center for Obesity Research and Education and professor of social and behavioral sciences, Temple University College of Public Health, Philadelphia, told this news organization. “There’s a subset of people who remain dissatisfied with their body image, including their shape.”
This body dissatisfaction of people who lose weight may be long-standing, predating the weight loss, or may be new because weight loss has catalyzed a host of previously unaddressed psychosocial issues. Some may show up at assessments on treatment onset, while others may be detected by monitoring changes during or after weight loss. “Mental health counseling after bariatric surgery is greatly underutilized,” Dr. Sarwer observed.
Ghost Fat
Research has corroborated the lingering self-perception of being “obese” vs “ex-obese.” In one study, patients who had undergone bariatric surgery reported being unable to see the difference in their size and shape 18-30 months following their procedure, despite substantial weight loss.
Some research suggests that rapid weight loss (eg, through bariatric surgery) is more likely to generate the perception of “phantom fat,” but additional research is needed to investigate whether the mode and speed of weight loss affect subsequent body image.
Being habituated to one’s former appearance may play a role, Dr. Sarwer suggested. “We see this not only with weight loss but with other body-altering procedures. It takes the brain time to catch up to the new appearance. In rhinoplasty, for example, it may take patients a while before they become accustomed to looking at their new face in the mirror after decades of looking at a more prominent nose.”
Years of Social Stigma
It may also take time for people to overcome years of enduring the stigma of obesity.
There are “pervasive” negative attitudes implying that individuals who are overweight and/or obese are “lazy, weak-willed, lacking in self-discipline and willpower” — a problem compounded by social media and media in general, which present unrealistic, glorified body images and disparaging messages about those with weight problems.
“Body image is a construct, rather than what you see in the mirror,” Sheethal Reddy, PhD, a psychologist at the Emory Bariatric Center, Emory University Hospital Midtown, Atlanta, told this news organization. “It’s the mental construct of our physical selves.”
According to Dr. Reddy, body image develops “within a broader societal context and is influenced by the person’s ethnic, racial, and cultural heritage.”
Adolescents are particularly vulnerable to body dissatisfaction. This is compounded in those with obesity, who often experience weight-based victimization and internalized weight-based stigma, compared with adolescents with lower weights. Weight stigma often takes the form of teasing and bullying.
“Appearance-related bullying and teasing during childhood and adolescence can reverberate into adulthood and persist throughout the lifespan,” Dr. Sarwer said. “When we see these patients and ask if they’ve ever been teased or bullied, not only do many say yes but it takes them back to those moments, to that origin story, and they remember someone saying something mean, cruel, and hurtful.”
Stigmatizing experiences can affect subjective body image, even after the weight has been lost and the person’s body is objectively thinner. Research comparing individuals who were overweight and lost weight to individuals who are currently overweight and haven’t lost weight and individuals who were never overweight suggests that “vestigial” body disparagement may persist following weight loss — especially in those with early-onset obesity.
The Role of Genetics
Genetics may contribute to people’s self-perception and body dissatisfaction, both before and after weight loss. A study of 827 community-based adolescents examined the association between polygenic risk scores (PRS) for body mass index (BMI) and type 2 diabetes and symptoms of body dissatisfaction and depression.
“Given the significant genetic role in BMI, we wanted to explore whether genetic risk for BMI might also predict body dissatisfaction,” lead author Krista Ekberg, MS, a doctoral candidate in clinical psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, told this news organization.
Genetic influences on BMI, as measured by PRS, were significantly associated with both phenotypic BMI and body dissatisfaction. “The association between PRS and body dissatisfaction was largely explained by BMI, suggesting that BMI itself accounts for much of the link between genetic risk and body dissatisfaction.”
Psychiatric History and Trauma
Adverse experiences, particularly sexual or physical abuse, may also account for body dissatisfaction after weight loss. “When some people with a history of this type of abuse lose a large amount of weight — typically after bariatric surgery — they often go through a period of emotional turbulence,” Dr. Sarwer said.
Childhood maltreatment can also be associated with body image disturbances in adulthood, according to a meta-analysis of 12 studies, encompassing 15,481 participants. Sexual abuse is “surprisingly common” among patients with obesity, according to Dr. Sarwer. A chart review of 131 patients revealed that 60% of those who reported a history of rape or sexual molestation were ≥ 50 pounds overweight vs only 28% of age- and sex-matched controls without a history of abuse. Other studies have corroborated these findings.
Excess weight can serve an “adaptive function,” Dr. Sarwer noted. It can be a self-protective mechanism that “insulates” them from sexual advances by potential romantic partners or abusers. Some may find that, after weight loss, repressed memories of a sexual assault surface as a result of the newer, more “attractive” appearance. Feeling vulnerable in their thinner bodies, they may need to regard themselves as overweight to maintain that feeling of “protection.” Weight loss may also trigger memories, flashbacks, or nightmares, as people return to a weight at which they were abused.
Dissociation is another mechanism linking trauma with post–weight loss body dysmorphia, Supatra Tovar, PsyD, RD, a clinical psychologist and registered dietitian with a practice in California, told this news organization. Dissociation from the body is often a coping mechanism for dealing with an overwhelming traumatic experience.
Individuals with a history of depression, anxiety, or posttraumatic stress disorder have higher levels of body dysmorphia, both before and after weight loss. One study found that patients undergoing bariatric surgery who had some type of psychopathology and other psychological risk factors were significantly more likely to report body image concerns 3 months after the surgery. Body image concerns were also more common in patients with preoperative depression, current psychotropic medication use, and a history of outpatient therapy or psychotropic medication use.
“Depression, anxiety, and trauma play a role in how you see yourself and how you carry yourself,” Dr. Reddy said. “This is wrapped up in any type of psychopathology. Being depressed is like looking at yourself through a cloud. It’s the opposite of ‘rose-colored glasses’ and instead, looking at yourself through a negative lens.”
Diagnosis and Interventions
Some helpful tools to assess the presence and extent of weight dissatisfaction and body dysmorphia include the Eating Disorder Inventory — Body Dissatisfaction Subscale and the Body Shape Questionnaire. It’s also important to take into account “the extent to which people are invested in their appearance psychologically,” Dr. Sarwer advised. The AO subscale of the Multidimensional Body-Self Relations Questionnaire generally assesses this. The Body Image Quality of Life Inventory assesses how and to what extent the perceived body image affects the person’s quality of life.
Experts recommend cognitive behavioral therapy (CBT) as an evidence-based intervention for body image issues, including those following weight loss.
“There’s an extensive CBT body image therapy program specifically tailored to the needs of overweight and obese individuals,” Dr. Sarwer said. “We don’t ignore historical variables that may have contributed to the problem, like early bullying, but we encourage people to think about what’s going on in their day-to-day life today. We drill down not only into the maladaptive behaviors but also the cognition and beliefs that may be erroneous but underlie these behaviors.”
The aim of CBT is to “modify irrational and dysfunctional thoughts, emotions, and behaviors through techniques such as self-monitoring, cognitive structuring, psychoeducation, desensitization, and exposure and response prevention.” The program laid out in Cash’s body image workbook includes eight steps. (Figure).
Weight Loss Doesn’t Automatically Equate With Happiness
Another realistic expectation runs counter to a common misperception that becoming thin will automatically translate into becoming happier. That’s not always the case, according to Dr. Tovar.
“If you haven’t worked deeply on addressing self-compassion and understanding that who you are at the core has nothing to do with your physical appearance, you can have an empty feeling once you’ve reached this point,” she said. “You still don’t know who you are and what you’re contributing to the world [because] you’ve been so focused on losing weight.”
Weight loss can also “unmask” questions about self-worth, even when receiving compliments about one’s “improved” appearance. “Praise and compliments after weight loss can be a double-edged sword,” Dr. Tovar observed. “You might think, ‘I wasn’t accepted or praised when I was overweight. The only way to be acceptable or validated is by losing weight, so I have to continue losing weight.’ ” This fuels fear of regaining the weight and can lead to continuing to see oneself as overweight, perhaps as a way to stay motivated to continue with weight loss. “Feeling that one’s value depends on remaining thin hampers body satisfaction,” she said.
Dr. Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life, encourages people to shift the emphasis from weight loss to a holistic focus on self-worth and to explore obstacles to those feelings both before and after weight loss.
Endocrinologists and other medical professionals can help by not engaging in “weight and body shaming,” Dr. Tovar said.
She recommends physicians “encourage patients to tune in to their own bodies, helping them become more aware of how different foods affect their physical and emotional well-being.”
Set realistic expectations through “open, nonjudgmental conversations about the complexities of metabolism, weight, and health.”
Dr. Tovar advises rather than focusing on weight loss as the primary goal, physicians should focus on health markers such as blood glucose, energy levels, mental well-being, and physical fitness.
Prioritize “listening over lecturing.” Begin with empathy, asking questions such as “How do you feel about your health right now? What changes have you noticed in your body lately?” Doing this “creates space for the patient to express their concerns without feeling judged or shamed.”
Refer patients to a mental health professional when a patient exhibits signs of disordered eating or poor body image or when emotional factors are playing a significant role in the relationship with food and weight. “If a patient is caught in a cycle of dieting and weight gain, struggles with binge eating, or displays symptoms of depression or anxiety related to body, then psychological help is crucial.”
Ultimately, the goal of treatment “should be to provide a safe, supportive environment where patients can heal — not just physically but also emotionally and mentally,” Dr. Tovar added.
Dr. Tovar, Ms. Ekberg, and Dr. Reddy reported no relevant financial relationships. Dr. Sarwer received grant funding from the National Institute of Dental and Craniofacial Research and National Institute of Diabetes and Digestive and Kidney Diseases. He has consulting relationships with Novo Nordisk and Twenty30 Health. He is an associate editor for Obesity Surgery and editor in chief of Obesity Science & Practice.
A version of this article first appeared on Medscape.com.
Many people who lose weight, whether through diet and lifestyle changes, medication, or bariatric surgery, recognize their body has changed. While they also experience improvements in quality of life and psychosocial areas, that’s not true for everyone. Some patients don’t “see” they’ve lost weight — a phenomenon referred to as “phantom fat,” “ghost fat,” or “vestigial body image.”
“Most people are happy with their appearance, or at least their body shape, after weight loss — although some are unhappy with the loose, sagging skin that can follow weight loss and seek plastic surgery to remedy that,” David B. Sarwer, PhD, director of the Center for Obesity Research and Education and professor of social and behavioral sciences, Temple University College of Public Health, Philadelphia, told this news organization. “There’s a subset of people who remain dissatisfied with their body image, including their shape.”
This body dissatisfaction of people who lose weight may be long-standing, predating the weight loss, or may be new because weight loss has catalyzed a host of previously unaddressed psychosocial issues. Some may show up at assessments on treatment onset, while others may be detected by monitoring changes during or after weight loss. “Mental health counseling after bariatric surgery is greatly underutilized,” Dr. Sarwer observed.
Ghost Fat
Research has corroborated the lingering self-perception of being “obese” vs “ex-obese.” In one study, patients who had undergone bariatric surgery reported being unable to see the difference in their size and shape 18-30 months following their procedure, despite substantial weight loss.
Some research suggests that rapid weight loss (eg, through bariatric surgery) is more likely to generate the perception of “phantom fat,” but additional research is needed to investigate whether the mode and speed of weight loss affect subsequent body image.
Being habituated to one’s former appearance may play a role, Dr. Sarwer suggested. “We see this not only with weight loss but with other body-altering procedures. It takes the brain time to catch up to the new appearance. In rhinoplasty, for example, it may take patients a while before they become accustomed to looking at their new face in the mirror after decades of looking at a more prominent nose.”
Years of Social Stigma
It may also take time for people to overcome years of enduring the stigma of obesity.
There are “pervasive” negative attitudes implying that individuals who are overweight and/or obese are “lazy, weak-willed, lacking in self-discipline and willpower” — a problem compounded by social media and media in general, which present unrealistic, glorified body images and disparaging messages about those with weight problems.
“Body image is a construct, rather than what you see in the mirror,” Sheethal Reddy, PhD, a psychologist at the Emory Bariatric Center, Emory University Hospital Midtown, Atlanta, told this news organization. “It’s the mental construct of our physical selves.”
According to Dr. Reddy, body image develops “within a broader societal context and is influenced by the person’s ethnic, racial, and cultural heritage.”
Adolescents are particularly vulnerable to body dissatisfaction. This is compounded in those with obesity, who often experience weight-based victimization and internalized weight-based stigma, compared with adolescents with lower weights. Weight stigma often takes the form of teasing and bullying.
“Appearance-related bullying and teasing during childhood and adolescence can reverberate into adulthood and persist throughout the lifespan,” Dr. Sarwer said. “When we see these patients and ask if they’ve ever been teased or bullied, not only do many say yes but it takes them back to those moments, to that origin story, and they remember someone saying something mean, cruel, and hurtful.”
Stigmatizing experiences can affect subjective body image, even after the weight has been lost and the person’s body is objectively thinner. Research comparing individuals who were overweight and lost weight to individuals who are currently overweight and haven’t lost weight and individuals who were never overweight suggests that “vestigial” body disparagement may persist following weight loss — especially in those with early-onset obesity.
The Role of Genetics
Genetics may contribute to people’s self-perception and body dissatisfaction, both before and after weight loss. A study of 827 community-based adolescents examined the association between polygenic risk scores (PRS) for body mass index (BMI) and type 2 diabetes and symptoms of body dissatisfaction and depression.
“Given the significant genetic role in BMI, we wanted to explore whether genetic risk for BMI might also predict body dissatisfaction,” lead author Krista Ekberg, MS, a doctoral candidate in clinical psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, told this news organization.
Genetic influences on BMI, as measured by PRS, were significantly associated with both phenotypic BMI and body dissatisfaction. “The association between PRS and body dissatisfaction was largely explained by BMI, suggesting that BMI itself accounts for much of the link between genetic risk and body dissatisfaction.”
Psychiatric History and Trauma
Adverse experiences, particularly sexual or physical abuse, may also account for body dissatisfaction after weight loss. “When some people with a history of this type of abuse lose a large amount of weight — typically after bariatric surgery — they often go through a period of emotional turbulence,” Dr. Sarwer said.
Childhood maltreatment can also be associated with body image disturbances in adulthood, according to a meta-analysis of 12 studies, encompassing 15,481 participants. Sexual abuse is “surprisingly common” among patients with obesity, according to Dr. Sarwer. A chart review of 131 patients revealed that 60% of those who reported a history of rape or sexual molestation were ≥ 50 pounds overweight vs only 28% of age- and sex-matched controls without a history of abuse. Other studies have corroborated these findings.
Excess weight can serve an “adaptive function,” Dr. Sarwer noted. It can be a self-protective mechanism that “insulates” them from sexual advances by potential romantic partners or abusers. Some may find that, after weight loss, repressed memories of a sexual assault surface as a result of the newer, more “attractive” appearance. Feeling vulnerable in their thinner bodies, they may need to regard themselves as overweight to maintain that feeling of “protection.” Weight loss may also trigger memories, flashbacks, or nightmares, as people return to a weight at which they were abused.
Dissociation is another mechanism linking trauma with post–weight loss body dysmorphia, Supatra Tovar, PsyD, RD, a clinical psychologist and registered dietitian with a practice in California, told this news organization. Dissociation from the body is often a coping mechanism for dealing with an overwhelming traumatic experience.
Individuals with a history of depression, anxiety, or posttraumatic stress disorder have higher levels of body dysmorphia, both before and after weight loss. One study found that patients undergoing bariatric surgery who had some type of psychopathology and other psychological risk factors were significantly more likely to report body image concerns 3 months after the surgery. Body image concerns were also more common in patients with preoperative depression, current psychotropic medication use, and a history of outpatient therapy or psychotropic medication use.
“Depression, anxiety, and trauma play a role in how you see yourself and how you carry yourself,” Dr. Reddy said. “This is wrapped up in any type of psychopathology. Being depressed is like looking at yourself through a cloud. It’s the opposite of ‘rose-colored glasses’ and instead, looking at yourself through a negative lens.”
Diagnosis and Interventions
Some helpful tools to assess the presence and extent of weight dissatisfaction and body dysmorphia include the Eating Disorder Inventory — Body Dissatisfaction Subscale and the Body Shape Questionnaire. It’s also important to take into account “the extent to which people are invested in their appearance psychologically,” Dr. Sarwer advised. The AO subscale of the Multidimensional Body-Self Relations Questionnaire generally assesses this. The Body Image Quality of Life Inventory assesses how and to what extent the perceived body image affects the person’s quality of life.
Experts recommend cognitive behavioral therapy (CBT) as an evidence-based intervention for body image issues, including those following weight loss.
“There’s an extensive CBT body image therapy program specifically tailored to the needs of overweight and obese individuals,” Dr. Sarwer said. “We don’t ignore historical variables that may have contributed to the problem, like early bullying, but we encourage people to think about what’s going on in their day-to-day life today. We drill down not only into the maladaptive behaviors but also the cognition and beliefs that may be erroneous but underlie these behaviors.”
The aim of CBT is to “modify irrational and dysfunctional thoughts, emotions, and behaviors through techniques such as self-monitoring, cognitive structuring, psychoeducation, desensitization, and exposure and response prevention.” The program laid out in Cash’s body image workbook includes eight steps. (Figure).
Weight Loss Doesn’t Automatically Equate With Happiness
Another realistic expectation runs counter to a common misperception that becoming thin will automatically translate into becoming happier. That’s not always the case, according to Dr. Tovar.
“If you haven’t worked deeply on addressing self-compassion and understanding that who you are at the core has nothing to do with your physical appearance, you can have an empty feeling once you’ve reached this point,” she said. “You still don’t know who you are and what you’re contributing to the world [because] you’ve been so focused on losing weight.”
Weight loss can also “unmask” questions about self-worth, even when receiving compliments about one’s “improved” appearance. “Praise and compliments after weight loss can be a double-edged sword,” Dr. Tovar observed. “You might think, ‘I wasn’t accepted or praised when I was overweight. The only way to be acceptable or validated is by losing weight, so I have to continue losing weight.’ ” This fuels fear of regaining the weight and can lead to continuing to see oneself as overweight, perhaps as a way to stay motivated to continue with weight loss. “Feeling that one’s value depends on remaining thin hampers body satisfaction,” she said.
Dr. Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life, encourages people to shift the emphasis from weight loss to a holistic focus on self-worth and to explore obstacles to those feelings both before and after weight loss.
Endocrinologists and other medical professionals can help by not engaging in “weight and body shaming,” Dr. Tovar said.
She recommends physicians “encourage patients to tune in to their own bodies, helping them become more aware of how different foods affect their physical and emotional well-being.”
Set realistic expectations through “open, nonjudgmental conversations about the complexities of metabolism, weight, and health.”
Dr. Tovar advises rather than focusing on weight loss as the primary goal, physicians should focus on health markers such as blood glucose, energy levels, mental well-being, and physical fitness.
Prioritize “listening over lecturing.” Begin with empathy, asking questions such as “How do you feel about your health right now? What changes have you noticed in your body lately?” Doing this “creates space for the patient to express their concerns without feeling judged or shamed.”
Refer patients to a mental health professional when a patient exhibits signs of disordered eating or poor body image or when emotional factors are playing a significant role in the relationship with food and weight. “If a patient is caught in a cycle of dieting and weight gain, struggles with binge eating, or displays symptoms of depression or anxiety related to body, then psychological help is crucial.”
Ultimately, the goal of treatment “should be to provide a safe, supportive environment where patients can heal — not just physically but also emotionally and mentally,” Dr. Tovar added.
Dr. Tovar, Ms. Ekberg, and Dr. Reddy reported no relevant financial relationships. Dr. Sarwer received grant funding from the National Institute of Dental and Craniofacial Research and National Institute of Diabetes and Digestive and Kidney Diseases. He has consulting relationships with Novo Nordisk and Twenty30 Health. He is an associate editor for Obesity Surgery and editor in chief of Obesity Science & Practice.
A version of this article first appeared on Medscape.com.
Many people who lose weight, whether through diet and lifestyle changes, medication, or bariatric surgery, recognize their body has changed. While they also experience improvements in quality of life and psychosocial areas, that’s not true for everyone. Some patients don’t “see” they’ve lost weight — a phenomenon referred to as “phantom fat,” “ghost fat,” or “vestigial body image.”
“Most people are happy with their appearance, or at least their body shape, after weight loss — although some are unhappy with the loose, sagging skin that can follow weight loss and seek plastic surgery to remedy that,” David B. Sarwer, PhD, director of the Center for Obesity Research and Education and professor of social and behavioral sciences, Temple University College of Public Health, Philadelphia, told this news organization. “There’s a subset of people who remain dissatisfied with their body image, including their shape.”
This body dissatisfaction of people who lose weight may be long-standing, predating the weight loss, or may be new because weight loss has catalyzed a host of previously unaddressed psychosocial issues. Some may show up at assessments on treatment onset, while others may be detected by monitoring changes during or after weight loss. “Mental health counseling after bariatric surgery is greatly underutilized,” Dr. Sarwer observed.
Ghost Fat
Research has corroborated the lingering self-perception of being “obese” vs “ex-obese.” In one study, patients who had undergone bariatric surgery reported being unable to see the difference in their size and shape 18-30 months following their procedure, despite substantial weight loss.
Some research suggests that rapid weight loss (eg, through bariatric surgery) is more likely to generate the perception of “phantom fat,” but additional research is needed to investigate whether the mode and speed of weight loss affect subsequent body image.
Being habituated to one’s former appearance may play a role, Dr. Sarwer suggested. “We see this not only with weight loss but with other body-altering procedures. It takes the brain time to catch up to the new appearance. In rhinoplasty, for example, it may take patients a while before they become accustomed to looking at their new face in the mirror after decades of looking at a more prominent nose.”
Years of Social Stigma
It may also take time for people to overcome years of enduring the stigma of obesity.
There are “pervasive” negative attitudes implying that individuals who are overweight and/or obese are “lazy, weak-willed, lacking in self-discipline and willpower” — a problem compounded by social media and media in general, which present unrealistic, glorified body images and disparaging messages about those with weight problems.
“Body image is a construct, rather than what you see in the mirror,” Sheethal Reddy, PhD, a psychologist at the Emory Bariatric Center, Emory University Hospital Midtown, Atlanta, told this news organization. “It’s the mental construct of our physical selves.”
According to Dr. Reddy, body image develops “within a broader societal context and is influenced by the person’s ethnic, racial, and cultural heritage.”
Adolescents are particularly vulnerable to body dissatisfaction. This is compounded in those with obesity, who often experience weight-based victimization and internalized weight-based stigma, compared with adolescents with lower weights. Weight stigma often takes the form of teasing and bullying.
“Appearance-related bullying and teasing during childhood and adolescence can reverberate into adulthood and persist throughout the lifespan,” Dr. Sarwer said. “When we see these patients and ask if they’ve ever been teased or bullied, not only do many say yes but it takes them back to those moments, to that origin story, and they remember someone saying something mean, cruel, and hurtful.”
Stigmatizing experiences can affect subjective body image, even after the weight has been lost and the person’s body is objectively thinner. Research comparing individuals who were overweight and lost weight to individuals who are currently overweight and haven’t lost weight and individuals who were never overweight suggests that “vestigial” body disparagement may persist following weight loss — especially in those with early-onset obesity.
The Role of Genetics
Genetics may contribute to people’s self-perception and body dissatisfaction, both before and after weight loss. A study of 827 community-based adolescents examined the association between polygenic risk scores (PRS) for body mass index (BMI) and type 2 diabetes and symptoms of body dissatisfaction and depression.
“Given the significant genetic role in BMI, we wanted to explore whether genetic risk for BMI might also predict body dissatisfaction,” lead author Krista Ekberg, MS, a doctoral candidate in clinical psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, told this news organization.
Genetic influences on BMI, as measured by PRS, were significantly associated with both phenotypic BMI and body dissatisfaction. “The association between PRS and body dissatisfaction was largely explained by BMI, suggesting that BMI itself accounts for much of the link between genetic risk and body dissatisfaction.”
Psychiatric History and Trauma
Adverse experiences, particularly sexual or physical abuse, may also account for body dissatisfaction after weight loss. “When some people with a history of this type of abuse lose a large amount of weight — typically after bariatric surgery — they often go through a period of emotional turbulence,” Dr. Sarwer said.
Childhood maltreatment can also be associated with body image disturbances in adulthood, according to a meta-analysis of 12 studies, encompassing 15,481 participants. Sexual abuse is “surprisingly common” among patients with obesity, according to Dr. Sarwer. A chart review of 131 patients revealed that 60% of those who reported a history of rape or sexual molestation were ≥ 50 pounds overweight vs only 28% of age- and sex-matched controls without a history of abuse. Other studies have corroborated these findings.
Excess weight can serve an “adaptive function,” Dr. Sarwer noted. It can be a self-protective mechanism that “insulates” them from sexual advances by potential romantic partners or abusers. Some may find that, after weight loss, repressed memories of a sexual assault surface as a result of the newer, more “attractive” appearance. Feeling vulnerable in their thinner bodies, they may need to regard themselves as overweight to maintain that feeling of “protection.” Weight loss may also trigger memories, flashbacks, or nightmares, as people return to a weight at which they were abused.
Dissociation is another mechanism linking trauma with post–weight loss body dysmorphia, Supatra Tovar, PsyD, RD, a clinical psychologist and registered dietitian with a practice in California, told this news organization. Dissociation from the body is often a coping mechanism for dealing with an overwhelming traumatic experience.
Individuals with a history of depression, anxiety, or posttraumatic stress disorder have higher levels of body dysmorphia, both before and after weight loss. One study found that patients undergoing bariatric surgery who had some type of psychopathology and other psychological risk factors were significantly more likely to report body image concerns 3 months after the surgery. Body image concerns were also more common in patients with preoperative depression, current psychotropic medication use, and a history of outpatient therapy or psychotropic medication use.
“Depression, anxiety, and trauma play a role in how you see yourself and how you carry yourself,” Dr. Reddy said. “This is wrapped up in any type of psychopathology. Being depressed is like looking at yourself through a cloud. It’s the opposite of ‘rose-colored glasses’ and instead, looking at yourself through a negative lens.”
Diagnosis and Interventions
Some helpful tools to assess the presence and extent of weight dissatisfaction and body dysmorphia include the Eating Disorder Inventory — Body Dissatisfaction Subscale and the Body Shape Questionnaire. It’s also important to take into account “the extent to which people are invested in their appearance psychologically,” Dr. Sarwer advised. The AO subscale of the Multidimensional Body-Self Relations Questionnaire generally assesses this. The Body Image Quality of Life Inventory assesses how and to what extent the perceived body image affects the person’s quality of life.
Experts recommend cognitive behavioral therapy (CBT) as an evidence-based intervention for body image issues, including those following weight loss.
“There’s an extensive CBT body image therapy program specifically tailored to the needs of overweight and obese individuals,” Dr. Sarwer said. “We don’t ignore historical variables that may have contributed to the problem, like early bullying, but we encourage people to think about what’s going on in their day-to-day life today. We drill down not only into the maladaptive behaviors but also the cognition and beliefs that may be erroneous but underlie these behaviors.”
The aim of CBT is to “modify irrational and dysfunctional thoughts, emotions, and behaviors through techniques such as self-monitoring, cognitive structuring, psychoeducation, desensitization, and exposure and response prevention.” The program laid out in Cash’s body image workbook includes eight steps. (Figure).
Weight Loss Doesn’t Automatically Equate With Happiness
Another realistic expectation runs counter to a common misperception that becoming thin will automatically translate into becoming happier. That’s not always the case, according to Dr. Tovar.
“If you haven’t worked deeply on addressing self-compassion and understanding that who you are at the core has nothing to do with your physical appearance, you can have an empty feeling once you’ve reached this point,” she said. “You still don’t know who you are and what you’re contributing to the world [because] you’ve been so focused on losing weight.”
Weight loss can also “unmask” questions about self-worth, even when receiving compliments about one’s “improved” appearance. “Praise and compliments after weight loss can be a double-edged sword,” Dr. Tovar observed. “You might think, ‘I wasn’t accepted or praised when I was overweight. The only way to be acceptable or validated is by losing weight, so I have to continue losing weight.’ ” This fuels fear of regaining the weight and can lead to continuing to see oneself as overweight, perhaps as a way to stay motivated to continue with weight loss. “Feeling that one’s value depends on remaining thin hampers body satisfaction,” she said.
Dr. Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life, encourages people to shift the emphasis from weight loss to a holistic focus on self-worth and to explore obstacles to those feelings both before and after weight loss.
Endocrinologists and other medical professionals can help by not engaging in “weight and body shaming,” Dr. Tovar said.
She recommends physicians “encourage patients to tune in to their own bodies, helping them become more aware of how different foods affect their physical and emotional well-being.”
Set realistic expectations through “open, nonjudgmental conversations about the complexities of metabolism, weight, and health.”
Dr. Tovar advises rather than focusing on weight loss as the primary goal, physicians should focus on health markers such as blood glucose, energy levels, mental well-being, and physical fitness.
Prioritize “listening over lecturing.” Begin with empathy, asking questions such as “How do you feel about your health right now? What changes have you noticed in your body lately?” Doing this “creates space for the patient to express their concerns without feeling judged or shamed.”
Refer patients to a mental health professional when a patient exhibits signs of disordered eating or poor body image or when emotional factors are playing a significant role in the relationship with food and weight. “If a patient is caught in a cycle of dieting and weight gain, struggles with binge eating, or displays symptoms of depression or anxiety related to body, then psychological help is crucial.”
Ultimately, the goal of treatment “should be to provide a safe, supportive environment where patients can heal — not just physically but also emotionally and mentally,” Dr. Tovar added.
Dr. Tovar, Ms. Ekberg, and Dr. Reddy reported no relevant financial relationships. Dr. Sarwer received grant funding from the National Institute of Dental and Craniofacial Research and National Institute of Diabetes and Digestive and Kidney Diseases. He has consulting relationships with Novo Nordisk and Twenty30 Health. He is an associate editor for Obesity Surgery and editor in chief of Obesity Science & Practice.
A version of this article first appeared on Medscape.com.
Why Residents Are Joining Unions in Droves
Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.
“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”
The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.
These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.
For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.
And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).
“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”
Here’s what residents are fighting for — right now.
Adequate Parental Leave
Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.
“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”
Contract negotiations here continue to be slow — and arduous.
“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”
If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.
“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
Fair Pay
In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.
“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”
This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.
Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.
“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.
“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
Adequate Healthcare
The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.
“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”
Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.
The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.
“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”
Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.
“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”
Paving the way for future residents is a key motivator, too.
“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”
A version of this article first appeared on Medscape.com.
Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.
“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”
The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.
These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.
For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.
And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).
“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”
Here’s what residents are fighting for — right now.
Adequate Parental Leave
Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.
“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”
Contract negotiations here continue to be slow — and arduous.
“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”
If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.
“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
Fair Pay
In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.
“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”
This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.
Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.
“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.
“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
Adequate Healthcare
The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.
“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”
Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.
The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.
“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”
Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.
“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”
Paving the way for future residents is a key motivator, too.
“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”
A version of this article first appeared on Medscape.com.
Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.
“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”
The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.
These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.
For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.
And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).
“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”
Here’s what residents are fighting for — right now.
Adequate Parental Leave
Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.
“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”
Contract negotiations here continue to be slow — and arduous.
“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”
If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.
“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
Fair Pay
In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.
“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”
This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.
Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.
“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.
“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
Adequate Healthcare
The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.
“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”
Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.
The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.
“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”
Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.
“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”
Paving the way for future residents is a key motivator, too.
“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”
A version of this article first appeared on Medscape.com.
Clozapine and Respiratory Infection Risk: What to Know
Clozapine is considered the drug of choice for treatment-resistant schizophrenia in guidelines globally, but it remains significantly underutilized. This is largely due to its range of side effects, particularly its increased infection risk which prompted the US Food and Drug Administration (FDA) to mandate regular blood testing to monitor neutrophil counts.
The COVID-19 pandemic raised new concerns about the care of clozapine-treated patients, leading clinicians and patients to urge the FDA to relax prescription requirements for the drug under the Risk Evaluation and Mitigation Strategy (REMS) program.
As the FDA prepares for a public hearing in November on proposed adjustments to the drug’s REMS criteria, a growing body of research is challenging the previous understanding of clozapine and infection risk.
Clarifying the Risk
Research on the link between clozapine and respiratory infections has produced conflicting results. Some studies indicate little to no increased risk for mild COVID-19 and other respiratory illnesses, while others have shown a higher likelihood of severe infection.
A recent nationwide Danish registry study of respiratory infections in people with a schizophrenia spectrum disorder could bring some clarity, Maxime Taquet, MD, a clinical lecturer at the University of Oxford, Warneford Hospital, Oxford, England, told this news organization.
By tracking periods when patients were on and off clozapine and other antipsychotics, the study offers more precise risk estimates, distinguishing the risks associated with the antipsychotic from those related to underlying schizophrenia, said Dr. Taquet, who authored an accompanying editorial on the study.
“It’s very important to try to disentangle the effects of schizophrenia, its severity, from the medication,” Dr. Taquet said. “I think that the Danish study is the first to try and really do that with as much precision as possible.”
After adjusting for key confounders including economic status and COVID-19 vaccination status, the researchers found that individuals taking antipsychotics had lower odds of testing positive for SARS-CoV-2 and similar rates of filled anti-infective prescriptions as those not taking the drugs.
Although antipsychotic use was not linked to higher rates of mild infection, it was linked to an increased risk for COVID-19 hospitalization in individuals older than 70 years, as well as hospitalization and death from other respiratory infections, mainly pneumonia, in those older than 40 years.
Notably, there was no excess risk for any outcome with clozapine vs other antipsychotics.
Strong Link to Pneumonia Risk
Results from a longitudinal Finnish study, just published in The American Journal of Psychiatry, also show an increased risk for severe outcomes from ileus and pneumonia among more than 2600 patients with schizophrenia taking clozapine.
Twenty years after initiating clozapine, the cumulative incidence estimate for ileus was 5.3% — more than sixfold higher than previously reported. The incidence of pneumonia was also high, at 29.5%.
Both illnesses were significantly associated with mortality, with odds ratios of 4.5 and 2.8, respectively.
These findings align with previous pharmacovigilance studies, with reported mortality rates for gastrointestinal hypomotility and pneumonia that were 4-10 times higher than those for agranulocytosis, the researchers said.
The study “really adds to a growing body of research suggesting a connection between clozapine use and a higher risk of developing pneumonia,” Robert O. Cotes, MD, a professor of psychiatry and behavioral sciences at Emory University, Atlanta, who specializes in the use of clozapine, told this news organization.
“Additionally, when people on clozapine do contract pneumonia, there’s concern the condition may be more dangerous,” he added.
A Closer Look at Neutropenia Risk
Neutropenia receives the lion’s share of attention among clozapine’s potential side effects, but this focus may need to be re-evaluated, Dr. Cotes said.
He pointed out that recent data suggest the risk for severe neutropenia, 2-3 years after initiating clozapine, is comparable to that of other antipsychotics.
A study of 26,630 clozapine users in Australia and New Zealand showed that most cases of severe neutropenia leading to clozapine cessation peaked within 18 weeks and was negligible after 2 years. This suggests weekly hematologic monitoring could potentially be discontinued after the 2-year mark.
Another study reported earlier this year by this news organization showed a low risk for mild or moderate neutropenia and no severe cases in nearly 1000 people taking clozapine.
“I worry that we may be missing the forest for the trees by hyperfocusing on neutropenia and not considering clozapine’s other potential serious side effects like pneumonia, myocarditis, and gastrointestinal hypermotility,” Dr. Cotes said.
Importance of Vaccines
The findings of these studies highlight the importance of vaccines in this at-risk group, said Dr. Taquet, a point emphasized by investigators of the Danish study he reviewed.
“Inspired by the experience of COVID-19 vaccine prioritization in severe mental illness and based on our findings, there is momentum for preventive action,” the authors wrote. “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group.”
This includes recommending pneumococcal, influenza, COVID-19, and other anti-infective vaccines in those older than 40 years treated with, or due to start, an antipsychotic.
“It’s not mandatory, but we do recommend that patients on clozapine get the regular vaccines,” Dr. Taquet said.
Pointing to the recent study on pneumonia risk, Dr. Cotes said addressing underlying risk factors, such as smoking, obesity, and possibly sedation and excessive salivation caused by clozapine, is key.
“And to make sure that vaccinations are up to date, particularly heading into this fall,” he added.
Rethinking Clozapine REMS
One of the most challenging issues facing clinicians and researchers is how to help people understand the safety profile of clozapine and to use it with more confidence, Dr. Cotes said.
“A lot of people hear about clozapine and they think about neutropenia, they think about side effects, the REMS system, and all of these factors really drive down clozapine utilization,” he said.
Treatment-resistant schizophrenia affects about a quarter of those with schizophrenia, yet only 4% of these patients receive clozapine in the United States, Dr. Cotes said. That number may be even lower for its other indication of reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.
The clozapine REMS is viewed as a major barrier to utilization and requires certification of pharmacists and physicians and use of a central system to monitor absolute neutrophil counts for neutropenia in patients.
As previously reported by this news organization in November 2022, the FDA opted to temporarily exercise enforcement discretion for certain aspects of the drug safety program to ensure continuity of care for patients after concerns were raised by the American Psychiatric Association (APA) along with other professional organizations.
Even with that temporary enforcement discretion, “reports have shown that over half of those prescribed clozapine have trouble accessing the medication because of the REMS program,” a spokesperson for the APA told this news organization.
“Not only are patients having trouble accessing the medication, many have trouble finding a prescriber in their geographic locations and others because of the monitoring requirements have their treatment discontinued leading to negative outcomes,” the spokesperson said.
The FDA is currently reviewing the clozapine REMS and is holding a joint advisory committee meeting on November 19 to discuss the review and “possible changes to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.”
The APA plans to submit written and oral comments to the advisory committees.
“We are hopeful that the re-evaluation meeting in November will remove barriers and increase access to clozapine, which is currently highly underutilized, especially in marginalized communities,” the spokesperson said.
Dr. Cotes reported serving as a speaker and consultant for Saladax Biomedical and as a consultant for Syneos Health. Dr. Taquet reported having no competing interests.
A version of this article first appeared on Medscape.com.
Clozapine is considered the drug of choice for treatment-resistant schizophrenia in guidelines globally, but it remains significantly underutilized. This is largely due to its range of side effects, particularly its increased infection risk which prompted the US Food and Drug Administration (FDA) to mandate regular blood testing to monitor neutrophil counts.
The COVID-19 pandemic raised new concerns about the care of clozapine-treated patients, leading clinicians and patients to urge the FDA to relax prescription requirements for the drug under the Risk Evaluation and Mitigation Strategy (REMS) program.
As the FDA prepares for a public hearing in November on proposed adjustments to the drug’s REMS criteria, a growing body of research is challenging the previous understanding of clozapine and infection risk.
Clarifying the Risk
Research on the link between clozapine and respiratory infections has produced conflicting results. Some studies indicate little to no increased risk for mild COVID-19 and other respiratory illnesses, while others have shown a higher likelihood of severe infection.
A recent nationwide Danish registry study of respiratory infections in people with a schizophrenia spectrum disorder could bring some clarity, Maxime Taquet, MD, a clinical lecturer at the University of Oxford, Warneford Hospital, Oxford, England, told this news organization.
By tracking periods when patients were on and off clozapine and other antipsychotics, the study offers more precise risk estimates, distinguishing the risks associated with the antipsychotic from those related to underlying schizophrenia, said Dr. Taquet, who authored an accompanying editorial on the study.
“It’s very important to try to disentangle the effects of schizophrenia, its severity, from the medication,” Dr. Taquet said. “I think that the Danish study is the first to try and really do that with as much precision as possible.”
After adjusting for key confounders including economic status and COVID-19 vaccination status, the researchers found that individuals taking antipsychotics had lower odds of testing positive for SARS-CoV-2 and similar rates of filled anti-infective prescriptions as those not taking the drugs.
Although antipsychotic use was not linked to higher rates of mild infection, it was linked to an increased risk for COVID-19 hospitalization in individuals older than 70 years, as well as hospitalization and death from other respiratory infections, mainly pneumonia, in those older than 40 years.
Notably, there was no excess risk for any outcome with clozapine vs other antipsychotics.
Strong Link to Pneumonia Risk
Results from a longitudinal Finnish study, just published in The American Journal of Psychiatry, also show an increased risk for severe outcomes from ileus and pneumonia among more than 2600 patients with schizophrenia taking clozapine.
Twenty years after initiating clozapine, the cumulative incidence estimate for ileus was 5.3% — more than sixfold higher than previously reported. The incidence of pneumonia was also high, at 29.5%.
Both illnesses were significantly associated with mortality, with odds ratios of 4.5 and 2.8, respectively.
These findings align with previous pharmacovigilance studies, with reported mortality rates for gastrointestinal hypomotility and pneumonia that were 4-10 times higher than those for agranulocytosis, the researchers said.
The study “really adds to a growing body of research suggesting a connection between clozapine use and a higher risk of developing pneumonia,” Robert O. Cotes, MD, a professor of psychiatry and behavioral sciences at Emory University, Atlanta, who specializes in the use of clozapine, told this news organization.
“Additionally, when people on clozapine do contract pneumonia, there’s concern the condition may be more dangerous,” he added.
A Closer Look at Neutropenia Risk
Neutropenia receives the lion’s share of attention among clozapine’s potential side effects, but this focus may need to be re-evaluated, Dr. Cotes said.
He pointed out that recent data suggest the risk for severe neutropenia, 2-3 years after initiating clozapine, is comparable to that of other antipsychotics.
A study of 26,630 clozapine users in Australia and New Zealand showed that most cases of severe neutropenia leading to clozapine cessation peaked within 18 weeks and was negligible after 2 years. This suggests weekly hematologic monitoring could potentially be discontinued after the 2-year mark.
Another study reported earlier this year by this news organization showed a low risk for mild or moderate neutropenia and no severe cases in nearly 1000 people taking clozapine.
“I worry that we may be missing the forest for the trees by hyperfocusing on neutropenia and not considering clozapine’s other potential serious side effects like pneumonia, myocarditis, and gastrointestinal hypermotility,” Dr. Cotes said.
Importance of Vaccines
The findings of these studies highlight the importance of vaccines in this at-risk group, said Dr. Taquet, a point emphasized by investigators of the Danish study he reviewed.
“Inspired by the experience of COVID-19 vaccine prioritization in severe mental illness and based on our findings, there is momentum for preventive action,” the authors wrote. “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group.”
This includes recommending pneumococcal, influenza, COVID-19, and other anti-infective vaccines in those older than 40 years treated with, or due to start, an antipsychotic.
“It’s not mandatory, but we do recommend that patients on clozapine get the regular vaccines,” Dr. Taquet said.
Pointing to the recent study on pneumonia risk, Dr. Cotes said addressing underlying risk factors, such as smoking, obesity, and possibly sedation and excessive salivation caused by clozapine, is key.
“And to make sure that vaccinations are up to date, particularly heading into this fall,” he added.
Rethinking Clozapine REMS
One of the most challenging issues facing clinicians and researchers is how to help people understand the safety profile of clozapine and to use it with more confidence, Dr. Cotes said.
“A lot of people hear about clozapine and they think about neutropenia, they think about side effects, the REMS system, and all of these factors really drive down clozapine utilization,” he said.
Treatment-resistant schizophrenia affects about a quarter of those with schizophrenia, yet only 4% of these patients receive clozapine in the United States, Dr. Cotes said. That number may be even lower for its other indication of reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.
The clozapine REMS is viewed as a major barrier to utilization and requires certification of pharmacists and physicians and use of a central system to monitor absolute neutrophil counts for neutropenia in patients.
As previously reported by this news organization in November 2022, the FDA opted to temporarily exercise enforcement discretion for certain aspects of the drug safety program to ensure continuity of care for patients after concerns were raised by the American Psychiatric Association (APA) along with other professional organizations.
Even with that temporary enforcement discretion, “reports have shown that over half of those prescribed clozapine have trouble accessing the medication because of the REMS program,” a spokesperson for the APA told this news organization.
“Not only are patients having trouble accessing the medication, many have trouble finding a prescriber in their geographic locations and others because of the monitoring requirements have their treatment discontinued leading to negative outcomes,” the spokesperson said.
The FDA is currently reviewing the clozapine REMS and is holding a joint advisory committee meeting on November 19 to discuss the review and “possible changes to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.”
The APA plans to submit written and oral comments to the advisory committees.
“We are hopeful that the re-evaluation meeting in November will remove barriers and increase access to clozapine, which is currently highly underutilized, especially in marginalized communities,” the spokesperson said.
Dr. Cotes reported serving as a speaker and consultant for Saladax Biomedical and as a consultant for Syneos Health. Dr. Taquet reported having no competing interests.
A version of this article first appeared on Medscape.com.
Clozapine is considered the drug of choice for treatment-resistant schizophrenia in guidelines globally, but it remains significantly underutilized. This is largely due to its range of side effects, particularly its increased infection risk which prompted the US Food and Drug Administration (FDA) to mandate regular blood testing to monitor neutrophil counts.
The COVID-19 pandemic raised new concerns about the care of clozapine-treated patients, leading clinicians and patients to urge the FDA to relax prescription requirements for the drug under the Risk Evaluation and Mitigation Strategy (REMS) program.
As the FDA prepares for a public hearing in November on proposed adjustments to the drug’s REMS criteria, a growing body of research is challenging the previous understanding of clozapine and infection risk.
Clarifying the Risk
Research on the link between clozapine and respiratory infections has produced conflicting results. Some studies indicate little to no increased risk for mild COVID-19 and other respiratory illnesses, while others have shown a higher likelihood of severe infection.
A recent nationwide Danish registry study of respiratory infections in people with a schizophrenia spectrum disorder could bring some clarity, Maxime Taquet, MD, a clinical lecturer at the University of Oxford, Warneford Hospital, Oxford, England, told this news organization.
By tracking periods when patients were on and off clozapine and other antipsychotics, the study offers more precise risk estimates, distinguishing the risks associated with the antipsychotic from those related to underlying schizophrenia, said Dr. Taquet, who authored an accompanying editorial on the study.
“It’s very important to try to disentangle the effects of schizophrenia, its severity, from the medication,” Dr. Taquet said. “I think that the Danish study is the first to try and really do that with as much precision as possible.”
After adjusting for key confounders including economic status and COVID-19 vaccination status, the researchers found that individuals taking antipsychotics had lower odds of testing positive for SARS-CoV-2 and similar rates of filled anti-infective prescriptions as those not taking the drugs.
Although antipsychotic use was not linked to higher rates of mild infection, it was linked to an increased risk for COVID-19 hospitalization in individuals older than 70 years, as well as hospitalization and death from other respiratory infections, mainly pneumonia, in those older than 40 years.
Notably, there was no excess risk for any outcome with clozapine vs other antipsychotics.
Strong Link to Pneumonia Risk
Results from a longitudinal Finnish study, just published in The American Journal of Psychiatry, also show an increased risk for severe outcomes from ileus and pneumonia among more than 2600 patients with schizophrenia taking clozapine.
Twenty years after initiating clozapine, the cumulative incidence estimate for ileus was 5.3% — more than sixfold higher than previously reported. The incidence of pneumonia was also high, at 29.5%.
Both illnesses were significantly associated with mortality, with odds ratios of 4.5 and 2.8, respectively.
These findings align with previous pharmacovigilance studies, with reported mortality rates for gastrointestinal hypomotility and pneumonia that were 4-10 times higher than those for agranulocytosis, the researchers said.
The study “really adds to a growing body of research suggesting a connection between clozapine use and a higher risk of developing pneumonia,” Robert O. Cotes, MD, a professor of psychiatry and behavioral sciences at Emory University, Atlanta, who specializes in the use of clozapine, told this news organization.
“Additionally, when people on clozapine do contract pneumonia, there’s concern the condition may be more dangerous,” he added.
A Closer Look at Neutropenia Risk
Neutropenia receives the lion’s share of attention among clozapine’s potential side effects, but this focus may need to be re-evaluated, Dr. Cotes said.
He pointed out that recent data suggest the risk for severe neutropenia, 2-3 years after initiating clozapine, is comparable to that of other antipsychotics.
A study of 26,630 clozapine users in Australia and New Zealand showed that most cases of severe neutropenia leading to clozapine cessation peaked within 18 weeks and was negligible after 2 years. This suggests weekly hematologic monitoring could potentially be discontinued after the 2-year mark.
Another study reported earlier this year by this news organization showed a low risk for mild or moderate neutropenia and no severe cases in nearly 1000 people taking clozapine.
“I worry that we may be missing the forest for the trees by hyperfocusing on neutropenia and not considering clozapine’s other potential serious side effects like pneumonia, myocarditis, and gastrointestinal hypermotility,” Dr. Cotes said.
Importance of Vaccines
The findings of these studies highlight the importance of vaccines in this at-risk group, said Dr. Taquet, a point emphasized by investigators of the Danish study he reviewed.
“Inspired by the experience of COVID-19 vaccine prioritization in severe mental illness and based on our findings, there is momentum for preventive action,” the authors wrote. “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group.”
This includes recommending pneumococcal, influenza, COVID-19, and other anti-infective vaccines in those older than 40 years treated with, or due to start, an antipsychotic.
“It’s not mandatory, but we do recommend that patients on clozapine get the regular vaccines,” Dr. Taquet said.
Pointing to the recent study on pneumonia risk, Dr. Cotes said addressing underlying risk factors, such as smoking, obesity, and possibly sedation and excessive salivation caused by clozapine, is key.
“And to make sure that vaccinations are up to date, particularly heading into this fall,” he added.
Rethinking Clozapine REMS
One of the most challenging issues facing clinicians and researchers is how to help people understand the safety profile of clozapine and to use it with more confidence, Dr. Cotes said.
“A lot of people hear about clozapine and they think about neutropenia, they think about side effects, the REMS system, and all of these factors really drive down clozapine utilization,” he said.
Treatment-resistant schizophrenia affects about a quarter of those with schizophrenia, yet only 4% of these patients receive clozapine in the United States, Dr. Cotes said. That number may be even lower for its other indication of reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.
The clozapine REMS is viewed as a major barrier to utilization and requires certification of pharmacists and physicians and use of a central system to monitor absolute neutrophil counts for neutropenia in patients.
As previously reported by this news organization in November 2022, the FDA opted to temporarily exercise enforcement discretion for certain aspects of the drug safety program to ensure continuity of care for patients after concerns were raised by the American Psychiatric Association (APA) along with other professional organizations.
Even with that temporary enforcement discretion, “reports have shown that over half of those prescribed clozapine have trouble accessing the medication because of the REMS program,” a spokesperson for the APA told this news organization.
“Not only are patients having trouble accessing the medication, many have trouble finding a prescriber in their geographic locations and others because of the monitoring requirements have their treatment discontinued leading to negative outcomes,” the spokesperson said.
The FDA is currently reviewing the clozapine REMS and is holding a joint advisory committee meeting on November 19 to discuss the review and “possible changes to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.”
The APA plans to submit written and oral comments to the advisory committees.
“We are hopeful that the re-evaluation meeting in November will remove barriers and increase access to clozapine, which is currently highly underutilized, especially in marginalized communities,” the spokesperson said.
Dr. Cotes reported serving as a speaker and consultant for Saladax Biomedical and as a consultant for Syneos Health. Dr. Taquet reported having no competing interests.
A version of this article first appeared on Medscape.com.
How Doctors Can Overcome Vaccine Hesitancy Through Empathy, Storytelling, and Patient-Centered Communication
When Kimberly Fisher, MD, was a junior doctor, she got fired up when patients showed hesitancy about vaccines. She responded by providing numbers, data, and facts that proved vaccines were safe and effective in preventing life-threatening diseases. But she soon realized that regurgitating scientific evidence wasn’t a winning strategy. “I’ve made the mistake of launching into a let me tell you all the things that I know that you don’t know kind of lecture,” Dr. Fisher, now an associate professor of medicine at UMass Chan Medical School, Worcester, Massachusetts, a pulmonary physician, and a researcher interested in patient-provider communication, told this news organization. “Through experience and research, I have learned that when you do that, they stop listening.”
She said when patients give reasons for not getting vaccinated that are factually wrong and rooted in misinformation, the most common reaction is to correct that information and not let it stand. “That is important; it just can’t be the first thing you do,” she said.
Diane Arnaout, MD, a pediatrician at Cook Children’s Pediatrics in Fort Worth, Texas, said listening to some patients explaining why vaccine injections are poisonous or a conspiracy can be exhausting and frustrating, but she agrees that presenting scientific facts alone won’t change people’s minds. “Even in my worst days, I take the time to stop talking for a moment and let the parents talk about what concerns them because if you just get mad and put a wall up, then that trust is gone, possibly forever, not just about vaccines.”
The Default Option
Since the start of the COVID-19 pandemic, Dr. Fisher has dedicated much of her time researching vaccine hesitancy. One of the most “fascinating and unexpected” findings of her work was that people are more likely to get vaccinated if a healthcare provider recommends that they get vaccinated in a “presumptive style,” which means that the provider uses language that presupposes that the person’s going to get vaccinated. “Rather than asking whether they wanted to get the vaccine conveying that the option of not getting it is just as valid, you make vaccination the default option,” she suggested.
The strategy wins many undecided, but it might not work on the most reluctant. “The presumptive recommendation is very directive, and if that works, great, but if it doesn’t, you need to shift to almost the opposite strategy, showing empathy and understanding about the person’s reasons for not wanting to be vaccinated,” Dr. Fisher said.
Find One Thing to Agree On
During a focus group on COVID-19 vaccine hesitancy that Dr. Fisher conducted in December 2021, most physicians expressed frustration that some patients remained resistant despite their best efforts. However, one participant shared an approach she found effective with even the most hesitant patients. The physician would listen carefully and express understanding, and even if what the patient said wasn’t accurate, she would find a kernel of truth to agree with and align herself with the patient. By doing this, she made patients feel like they were a team.
The example she gave was if a patient said, “I don’t know. I’ve heard different things and don’t feel comfortable taking the vaccine,” she might respond with something like, “I think it’s great that you’re thinking critically about this before making a decision. I was the same way — I wanted to fully understand the data before getting vaccinated. I also wouldn’t want to take something if I thought it wasn’t safe. It’s good that you’re being thorough.” Acknowledging their careful thought process, the physician helped patients feel seen and understood only after she introduced additional information to guide them toward understanding why the vaccine might be beneficial.
Focus on the Disease
Dr. Arnaout’s frustration grows when at the end of an appointment some parents object to vaccines with irrational and misguided concerns. “You’ve trusted me with everything else we’ve discussed today — whether it’s a diaper rash or an ear infection — so why wouldn’t you trust me on this? Sometimes it feels almost offensive — why trust my medical expertise on everything else but not vaccines?” she said.
The answer, she believes, is that vaccines are preventive, and when the threat of disease feels distant, it’s hard to see the necessity of a painful shot for your healthy child. “But if your baby were dying from meningitis, the needles we use to deliver life-saving medications in the hospital would feel absolutely necessary. It’s hard as a parent to inflict pain for something you’ve never personally seen.”
Dr. Arnaout thinks it is important to bring the focus on the disease the vaccine prevents. “Let’s talk about measles — how if a baby in my waiting room has measles and coughs, the virus can stay suspended in the air for 2 hours, and 100% of unvaccinated people in that room will get measles.”
She said sharing personal stories can also help physicians connect with their patients. “I talk to parents every day about their vaccine concerns, and I’ve found that if I take the time to explain why we vaccinate, they start to understand. I also tell them, ‘I vaccinated my children for everything on time and give them the flu shot every year. Why would I offer your child something I wouldn’t give my own?’ That personal decision, made without hesitation, resonates with parents.”
Wired for Stories
Medical professionals have a professional necessity to think and speak with precision. Their training is based on analyzing studies and data, and they develop a specialized vocabulary to describe their findings accurately.
But the human brain is naturally inclined to process and make sense of information through the structure and narrative of stories. We instinctively organize reality into a “shape of a story” rather than just isolated facts, explained Ben Riggs, senior communications specialist at Kettering Health, Dayton, Ohio, a nonfiction writing coach and author. Storytelling also taps into the emotional, rather than just the rational, parts of the brain. This emotional connection helps make the information more memorable and impactful for the listener.
Mr. Riggs said that moving from this world of precision and accuracy to one that also requires effective communication with those who haven’t had that same training is much like learning a new language. “If they can’t speak in a way that non-scientists understand, it’s like the old saying: If a tree falls in the woods and no one hears it, does it make a sound?”
Metaphors can help doctors translate scientific facts into language that meets people where they are, allowing patients to make informed decisions about their health. They can help physicians transform abstract concepts into vivid, tangible mental images that are easier for people to understand and relate to, Mr. Riggs explained. “We are predominantly concrete thinkers. Metaphors can create concrete scenes and do much of the heavy lifting when communicating complex ideas.”
“It’s important to align yourself with the other person by showing that you care, that you’re truly listening, and understand their perspective,” concluded Dr. Fisher. “Acknowledge their point of view and emphasize that they have autonomy in the decision-making process. This can open people up to hearing your perspective. You also need to know when to let go don’t cause a rift in the relationship.”
Dr. Fisher, Dr. Arnaout, and Mr. Riggs reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When Kimberly Fisher, MD, was a junior doctor, she got fired up when patients showed hesitancy about vaccines. She responded by providing numbers, data, and facts that proved vaccines were safe and effective in preventing life-threatening diseases. But she soon realized that regurgitating scientific evidence wasn’t a winning strategy. “I’ve made the mistake of launching into a let me tell you all the things that I know that you don’t know kind of lecture,” Dr. Fisher, now an associate professor of medicine at UMass Chan Medical School, Worcester, Massachusetts, a pulmonary physician, and a researcher interested in patient-provider communication, told this news organization. “Through experience and research, I have learned that when you do that, they stop listening.”
She said when patients give reasons for not getting vaccinated that are factually wrong and rooted in misinformation, the most common reaction is to correct that information and not let it stand. “That is important; it just can’t be the first thing you do,” she said.
Diane Arnaout, MD, a pediatrician at Cook Children’s Pediatrics in Fort Worth, Texas, said listening to some patients explaining why vaccine injections are poisonous or a conspiracy can be exhausting and frustrating, but she agrees that presenting scientific facts alone won’t change people’s minds. “Even in my worst days, I take the time to stop talking for a moment and let the parents talk about what concerns them because if you just get mad and put a wall up, then that trust is gone, possibly forever, not just about vaccines.”
The Default Option
Since the start of the COVID-19 pandemic, Dr. Fisher has dedicated much of her time researching vaccine hesitancy. One of the most “fascinating and unexpected” findings of her work was that people are more likely to get vaccinated if a healthcare provider recommends that they get vaccinated in a “presumptive style,” which means that the provider uses language that presupposes that the person’s going to get vaccinated. “Rather than asking whether they wanted to get the vaccine conveying that the option of not getting it is just as valid, you make vaccination the default option,” she suggested.
The strategy wins many undecided, but it might not work on the most reluctant. “The presumptive recommendation is very directive, and if that works, great, but if it doesn’t, you need to shift to almost the opposite strategy, showing empathy and understanding about the person’s reasons for not wanting to be vaccinated,” Dr. Fisher said.
Find One Thing to Agree On
During a focus group on COVID-19 vaccine hesitancy that Dr. Fisher conducted in December 2021, most physicians expressed frustration that some patients remained resistant despite their best efforts. However, one participant shared an approach she found effective with even the most hesitant patients. The physician would listen carefully and express understanding, and even if what the patient said wasn’t accurate, she would find a kernel of truth to agree with and align herself with the patient. By doing this, she made patients feel like they were a team.
The example she gave was if a patient said, “I don’t know. I’ve heard different things and don’t feel comfortable taking the vaccine,” she might respond with something like, “I think it’s great that you’re thinking critically about this before making a decision. I was the same way — I wanted to fully understand the data before getting vaccinated. I also wouldn’t want to take something if I thought it wasn’t safe. It’s good that you’re being thorough.” Acknowledging their careful thought process, the physician helped patients feel seen and understood only after she introduced additional information to guide them toward understanding why the vaccine might be beneficial.
Focus on the Disease
Dr. Arnaout’s frustration grows when at the end of an appointment some parents object to vaccines with irrational and misguided concerns. “You’ve trusted me with everything else we’ve discussed today — whether it’s a diaper rash or an ear infection — so why wouldn’t you trust me on this? Sometimes it feels almost offensive — why trust my medical expertise on everything else but not vaccines?” she said.
The answer, she believes, is that vaccines are preventive, and when the threat of disease feels distant, it’s hard to see the necessity of a painful shot for your healthy child. “But if your baby were dying from meningitis, the needles we use to deliver life-saving medications in the hospital would feel absolutely necessary. It’s hard as a parent to inflict pain for something you’ve never personally seen.”
Dr. Arnaout thinks it is important to bring the focus on the disease the vaccine prevents. “Let’s talk about measles — how if a baby in my waiting room has measles and coughs, the virus can stay suspended in the air for 2 hours, and 100% of unvaccinated people in that room will get measles.”
She said sharing personal stories can also help physicians connect with their patients. “I talk to parents every day about their vaccine concerns, and I’ve found that if I take the time to explain why we vaccinate, they start to understand. I also tell them, ‘I vaccinated my children for everything on time and give them the flu shot every year. Why would I offer your child something I wouldn’t give my own?’ That personal decision, made without hesitation, resonates with parents.”
Wired for Stories
Medical professionals have a professional necessity to think and speak with precision. Their training is based on analyzing studies and data, and they develop a specialized vocabulary to describe their findings accurately.
But the human brain is naturally inclined to process and make sense of information through the structure and narrative of stories. We instinctively organize reality into a “shape of a story” rather than just isolated facts, explained Ben Riggs, senior communications specialist at Kettering Health, Dayton, Ohio, a nonfiction writing coach and author. Storytelling also taps into the emotional, rather than just the rational, parts of the brain. This emotional connection helps make the information more memorable and impactful for the listener.
Mr. Riggs said that moving from this world of precision and accuracy to one that also requires effective communication with those who haven’t had that same training is much like learning a new language. “If they can’t speak in a way that non-scientists understand, it’s like the old saying: If a tree falls in the woods and no one hears it, does it make a sound?”
Metaphors can help doctors translate scientific facts into language that meets people where they are, allowing patients to make informed decisions about their health. They can help physicians transform abstract concepts into vivid, tangible mental images that are easier for people to understand and relate to, Mr. Riggs explained. “We are predominantly concrete thinkers. Metaphors can create concrete scenes and do much of the heavy lifting when communicating complex ideas.”
“It’s important to align yourself with the other person by showing that you care, that you’re truly listening, and understand their perspective,” concluded Dr. Fisher. “Acknowledge their point of view and emphasize that they have autonomy in the decision-making process. This can open people up to hearing your perspective. You also need to know when to let go don’t cause a rift in the relationship.”
Dr. Fisher, Dr. Arnaout, and Mr. Riggs reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When Kimberly Fisher, MD, was a junior doctor, she got fired up when patients showed hesitancy about vaccines. She responded by providing numbers, data, and facts that proved vaccines were safe and effective in preventing life-threatening diseases. But she soon realized that regurgitating scientific evidence wasn’t a winning strategy. “I’ve made the mistake of launching into a let me tell you all the things that I know that you don’t know kind of lecture,” Dr. Fisher, now an associate professor of medicine at UMass Chan Medical School, Worcester, Massachusetts, a pulmonary physician, and a researcher interested in patient-provider communication, told this news organization. “Through experience and research, I have learned that when you do that, they stop listening.”
She said when patients give reasons for not getting vaccinated that are factually wrong and rooted in misinformation, the most common reaction is to correct that information and not let it stand. “That is important; it just can’t be the first thing you do,” she said.
Diane Arnaout, MD, a pediatrician at Cook Children’s Pediatrics in Fort Worth, Texas, said listening to some patients explaining why vaccine injections are poisonous or a conspiracy can be exhausting and frustrating, but she agrees that presenting scientific facts alone won’t change people’s minds. “Even in my worst days, I take the time to stop talking for a moment and let the parents talk about what concerns them because if you just get mad and put a wall up, then that trust is gone, possibly forever, not just about vaccines.”
The Default Option
Since the start of the COVID-19 pandemic, Dr. Fisher has dedicated much of her time researching vaccine hesitancy. One of the most “fascinating and unexpected” findings of her work was that people are more likely to get vaccinated if a healthcare provider recommends that they get vaccinated in a “presumptive style,” which means that the provider uses language that presupposes that the person’s going to get vaccinated. “Rather than asking whether they wanted to get the vaccine conveying that the option of not getting it is just as valid, you make vaccination the default option,” she suggested.
The strategy wins many undecided, but it might not work on the most reluctant. “The presumptive recommendation is very directive, and if that works, great, but if it doesn’t, you need to shift to almost the opposite strategy, showing empathy and understanding about the person’s reasons for not wanting to be vaccinated,” Dr. Fisher said.
Find One Thing to Agree On
During a focus group on COVID-19 vaccine hesitancy that Dr. Fisher conducted in December 2021, most physicians expressed frustration that some patients remained resistant despite their best efforts. However, one participant shared an approach she found effective with even the most hesitant patients. The physician would listen carefully and express understanding, and even if what the patient said wasn’t accurate, she would find a kernel of truth to agree with and align herself with the patient. By doing this, she made patients feel like they were a team.
The example she gave was if a patient said, “I don’t know. I’ve heard different things and don’t feel comfortable taking the vaccine,” she might respond with something like, “I think it’s great that you’re thinking critically about this before making a decision. I was the same way — I wanted to fully understand the data before getting vaccinated. I also wouldn’t want to take something if I thought it wasn’t safe. It’s good that you’re being thorough.” Acknowledging their careful thought process, the physician helped patients feel seen and understood only after she introduced additional information to guide them toward understanding why the vaccine might be beneficial.
Focus on the Disease
Dr. Arnaout’s frustration grows when at the end of an appointment some parents object to vaccines with irrational and misguided concerns. “You’ve trusted me with everything else we’ve discussed today — whether it’s a diaper rash or an ear infection — so why wouldn’t you trust me on this? Sometimes it feels almost offensive — why trust my medical expertise on everything else but not vaccines?” she said.
The answer, she believes, is that vaccines are preventive, and when the threat of disease feels distant, it’s hard to see the necessity of a painful shot for your healthy child. “But if your baby were dying from meningitis, the needles we use to deliver life-saving medications in the hospital would feel absolutely necessary. It’s hard as a parent to inflict pain for something you’ve never personally seen.”
Dr. Arnaout thinks it is important to bring the focus on the disease the vaccine prevents. “Let’s talk about measles — how if a baby in my waiting room has measles and coughs, the virus can stay suspended in the air for 2 hours, and 100% of unvaccinated people in that room will get measles.”
She said sharing personal stories can also help physicians connect with their patients. “I talk to parents every day about their vaccine concerns, and I’ve found that if I take the time to explain why we vaccinate, they start to understand. I also tell them, ‘I vaccinated my children for everything on time and give them the flu shot every year. Why would I offer your child something I wouldn’t give my own?’ That personal decision, made without hesitation, resonates with parents.”
Wired for Stories
Medical professionals have a professional necessity to think and speak with precision. Their training is based on analyzing studies and data, and they develop a specialized vocabulary to describe their findings accurately.
But the human brain is naturally inclined to process and make sense of information through the structure and narrative of stories. We instinctively organize reality into a “shape of a story” rather than just isolated facts, explained Ben Riggs, senior communications specialist at Kettering Health, Dayton, Ohio, a nonfiction writing coach and author. Storytelling also taps into the emotional, rather than just the rational, parts of the brain. This emotional connection helps make the information more memorable and impactful for the listener.
Mr. Riggs said that moving from this world of precision and accuracy to one that also requires effective communication with those who haven’t had that same training is much like learning a new language. “If they can’t speak in a way that non-scientists understand, it’s like the old saying: If a tree falls in the woods and no one hears it, does it make a sound?”
Metaphors can help doctors translate scientific facts into language that meets people where they are, allowing patients to make informed decisions about their health. They can help physicians transform abstract concepts into vivid, tangible mental images that are easier for people to understand and relate to, Mr. Riggs explained. “We are predominantly concrete thinkers. Metaphors can create concrete scenes and do much of the heavy lifting when communicating complex ideas.”
“It’s important to align yourself with the other person by showing that you care, that you’re truly listening, and understand their perspective,” concluded Dr. Fisher. “Acknowledge their point of view and emphasize that they have autonomy in the decision-making process. This can open people up to hearing your perspective. You also need to know when to let go don’t cause a rift in the relationship.”
Dr. Fisher, Dr. Arnaout, and Mr. Riggs reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.