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Minor Progress in Gender Pay Equity, But a Big Gap Persists
Despite some recent progress in compensation equity, women in medicine continue to be paid significantly lower salaries than men.
According to the Female Compensation Report 2024 by Medscape, male doctors of any kind earned an average salary of about $400,000, whereas female doctors earned approximately $309,000 — a 29% gap.
The report analyzed survey data from 7000 practicing physicians who were recruited over a 4-month period starting in October 2023. The respondents comprised roughly 60% women representing over 29 specialties.
In the 2022 report, the pay gap between the genders was 32%. But some women in the field argued substantial headway is still needed.
“You can try and pick apart the data, but I’d say we’re not really making progress,” said Susan T. Hingle, MD, an internist in Illinois and president of the American Medical Women’s Association. “A decline by a couple of percentage points is not significantly addressing this pay gap that over a lifetime is huge, can be millions of dollars.”
The gender gap was narrower among female primary care physicians (PCPs) vs medical specialists. Female PCPs earned around $253,000 per year, whereas male PCPs earned about $295,000 per year. Hingle suggested that female PCPs may enjoy more pay equity because health systems have a harder time filling these positions.
On the other hand, the gap for specialists rose from 27% in 2022 to 31% in 2023. Differences in how aggressively women and men negotiate compensation packages may play a role, said Hingle.
“Taking negotiation out of the equation would be progress to me,” said Hingle.
Pay disparity did not appear to be the result of time spent on the job — female doctors reported an average of 49 work hours per week, whereas their male counterparts reported 50 work hours per week.
Meanwhile, the pay gap progressively worsened over time. Among doctors aged 28-34 years, men earned an average of $53,000 more than women. By ages 46-49, men earned an average of $157,000 more than women.
“I had to take my employer to court to get equal compensation, sad as it is to say,” said a hospitalist in North Carolina.
Nearly 60% of women surveyed felt they were not being paid fairly for their efforts, up from less than half reported in Medscape’s 2021 report. Hingle said that this figure may not only reflect sentiments about the compensation gap, but also less support on the job, including fewer physician assistants (PAs), nurses, and administrative staff.
“At my job, I do the work of multiple people,” said a survey respondent. “Junior resident, senior resident, social worker, nurse practitioner, PA — as well as try to be a teacher, researcher, [and] an excellent doctor and have the time to make patients feel as if they are not in a rush.”
Roughly 30% of women physicians said they would not choose to go into medicine again if given the chance compared with 26% of male physicians.
“Gender inequities in our profession have a direct impact,” said Shikha Jain, MD, an oncologist in Chicago and founder of the Women in Medicine nonprofit. “I think women in general don’t feel valued in the care they’re providing.”
Jain cited bullying, harassment, and fewer opportunities for leadership and recognition as factors beyond pay that affect female physicians’ feelings of being valued.
A version of this article first appeared on Medscape.com.
Despite some recent progress in compensation equity, women in medicine continue to be paid significantly lower salaries than men.
According to the Female Compensation Report 2024 by Medscape, male doctors of any kind earned an average salary of about $400,000, whereas female doctors earned approximately $309,000 — a 29% gap.
The report analyzed survey data from 7000 practicing physicians who were recruited over a 4-month period starting in October 2023. The respondents comprised roughly 60% women representing over 29 specialties.
In the 2022 report, the pay gap between the genders was 32%. But some women in the field argued substantial headway is still needed.
“You can try and pick apart the data, but I’d say we’re not really making progress,” said Susan T. Hingle, MD, an internist in Illinois and president of the American Medical Women’s Association. “A decline by a couple of percentage points is not significantly addressing this pay gap that over a lifetime is huge, can be millions of dollars.”
The gender gap was narrower among female primary care physicians (PCPs) vs medical specialists. Female PCPs earned around $253,000 per year, whereas male PCPs earned about $295,000 per year. Hingle suggested that female PCPs may enjoy more pay equity because health systems have a harder time filling these positions.
On the other hand, the gap for specialists rose from 27% in 2022 to 31% in 2023. Differences in how aggressively women and men negotiate compensation packages may play a role, said Hingle.
“Taking negotiation out of the equation would be progress to me,” said Hingle.
Pay disparity did not appear to be the result of time spent on the job — female doctors reported an average of 49 work hours per week, whereas their male counterparts reported 50 work hours per week.
Meanwhile, the pay gap progressively worsened over time. Among doctors aged 28-34 years, men earned an average of $53,000 more than women. By ages 46-49, men earned an average of $157,000 more than women.
“I had to take my employer to court to get equal compensation, sad as it is to say,” said a hospitalist in North Carolina.
Nearly 60% of women surveyed felt they were not being paid fairly for their efforts, up from less than half reported in Medscape’s 2021 report. Hingle said that this figure may not only reflect sentiments about the compensation gap, but also less support on the job, including fewer physician assistants (PAs), nurses, and administrative staff.
“At my job, I do the work of multiple people,” said a survey respondent. “Junior resident, senior resident, social worker, nurse practitioner, PA — as well as try to be a teacher, researcher, [and] an excellent doctor and have the time to make patients feel as if they are not in a rush.”
Roughly 30% of women physicians said they would not choose to go into medicine again if given the chance compared with 26% of male physicians.
“Gender inequities in our profession have a direct impact,” said Shikha Jain, MD, an oncologist in Chicago and founder of the Women in Medicine nonprofit. “I think women in general don’t feel valued in the care they’re providing.”
Jain cited bullying, harassment, and fewer opportunities for leadership and recognition as factors beyond pay that affect female physicians’ feelings of being valued.
A version of this article first appeared on Medscape.com.
Despite some recent progress in compensation equity, women in medicine continue to be paid significantly lower salaries than men.
According to the Female Compensation Report 2024 by Medscape, male doctors of any kind earned an average salary of about $400,000, whereas female doctors earned approximately $309,000 — a 29% gap.
The report analyzed survey data from 7000 practicing physicians who were recruited over a 4-month period starting in October 2023. The respondents comprised roughly 60% women representing over 29 specialties.
In the 2022 report, the pay gap between the genders was 32%. But some women in the field argued substantial headway is still needed.
“You can try and pick apart the data, but I’d say we’re not really making progress,” said Susan T. Hingle, MD, an internist in Illinois and president of the American Medical Women’s Association. “A decline by a couple of percentage points is not significantly addressing this pay gap that over a lifetime is huge, can be millions of dollars.”
The gender gap was narrower among female primary care physicians (PCPs) vs medical specialists. Female PCPs earned around $253,000 per year, whereas male PCPs earned about $295,000 per year. Hingle suggested that female PCPs may enjoy more pay equity because health systems have a harder time filling these positions.
On the other hand, the gap for specialists rose from 27% in 2022 to 31% in 2023. Differences in how aggressively women and men negotiate compensation packages may play a role, said Hingle.
“Taking negotiation out of the equation would be progress to me,” said Hingle.
Pay disparity did not appear to be the result of time spent on the job — female doctors reported an average of 49 work hours per week, whereas their male counterparts reported 50 work hours per week.
Meanwhile, the pay gap progressively worsened over time. Among doctors aged 28-34 years, men earned an average of $53,000 more than women. By ages 46-49, men earned an average of $157,000 more than women.
“I had to take my employer to court to get equal compensation, sad as it is to say,” said a hospitalist in North Carolina.
Nearly 60% of women surveyed felt they were not being paid fairly for their efforts, up from less than half reported in Medscape’s 2021 report. Hingle said that this figure may not only reflect sentiments about the compensation gap, but also less support on the job, including fewer physician assistants (PAs), nurses, and administrative staff.
“At my job, I do the work of multiple people,” said a survey respondent. “Junior resident, senior resident, social worker, nurse practitioner, PA — as well as try to be a teacher, researcher, [and] an excellent doctor and have the time to make patients feel as if they are not in a rush.”
Roughly 30% of women physicians said they would not choose to go into medicine again if given the chance compared with 26% of male physicians.
“Gender inequities in our profession have a direct impact,” said Shikha Jain, MD, an oncologist in Chicago and founder of the Women in Medicine nonprofit. “I think women in general don’t feel valued in the care they’re providing.”
Jain cited bullying, harassment, and fewer opportunities for leadership and recognition as factors beyond pay that affect female physicians’ feelings of being valued.
A version of this article first appeared on Medscape.com.
Which Specialists Should Lead BP Control Efforts?
Current efforts to control high blood pressure (BP) are failing in the United States and globally.
The first World Health Organization (WHO) global report on hypertension found that only 54% of adults with hypertension are diagnosed, 42% get treatment, and just 21% have their hypertension controlled.
In the United States, almost half (48%) of adults have high BP, defined as a systolic BP > 130 mm Hg, or a diastolic BP > 80 mm Hg, or are taking medication for high BP, according to the Centers for Disease Control and Prevention. Only about one in four adults (22.5%) with high BP have their BP under control.
High BP is a major risk factor for coronary heart disease, heart failure, and stroke, and the problem of controlling it is only getting worse. In 2024, the American Heart Association estimates that, “among adults, prevalence of hypertension will increase from 51.2% in 2020 to 61.0% in 2050.”
Pharmacists Most Effective
Though many factors contribute to hypertension, researchers have found that the kind of specialist leading the hypertension team may play a role in success. Currently, most BP control teams are led by physicians in primary care.
In a recent meta-analysis involving 100 randomized controlled trials and more than 90,000 patients in Circulation, Katherine T. Mills, PhD, School of Public Health, Tulane University, New Orleans, Louisiana, and colleagues found that, while all the groups studied who led BP control efforts were successful in reducing BP, pharmacist- and community health worker–led teams saw the biggest reductions.
Those groups’ efforts resulted in the greatest systolic BP drops: −7.3 mm Hg (pharmacists) and −7.1 mm Hg (community health workers). Groups led by nurses and physicians saw systolic changes of −3 and −2.4 mm Hg, respectively.
Similarly, pharmacist- and community health worker–led efforts saw the greatest diastolic BP reductions (−3.8 and −3.1 mm Hg), compared with nurse-led (−1.6) and physician-led (−1.2) efforts.
Reductions Enough to Cut Cardiovascular Disease Risk
The reduction numbers for pharmacists are clinically meaningful, Mills said in an interview. “It’s greater than a lot of what we see from individual lifestyle changes,” such as reducing sodium intake or increasing physical activity.
“It’s a big enough blood pressure change to have meaningful reduction in risk of cardiovascular disease,” she said.
This evidence that the leader of the team matters is particularly important because the treatment of hypertension is not in doubt. Something else is not working the way it should.
“We have basically all the scientific evidence we need in terms of what interventions work. But there’s a big gap between that and what’s actually being done in the real world,” she said.
Mills said she was not surprised that pharmacists got the best results “because so much of it has to do with titrating medications and finding the right kind of medications for each patient.”
Additionally, BP management and control falls right into pharmacists’ wheelhouse, Mills noted, including evaluating medication side effects and talking to patients about medication adherence.
Why Pharmacists May Be More Successful
In an accompanying editorial, Ross T. Tsuyuki, PharmD, with the EPICORE Centre, Division of Cardiology, University of Alberta in Edmonton, Canada, and coauthors said the Mills study provides further data to support pharmacists leading BP control efforts, but it’s not the data that have been keeping the model from changing. The barriers include turf wars and lack of legislative change.
The editorialists also said having pharmacist-led BP teams is only the first step. “We need pharmacists to independently prescribe,” they wrote.
“Since individual states govern the scope of practice of pharmacists,” the editorialists wrote, “we have the enormous task of changing regulations to allow pharmacists to independently prescribe for hypertension. But it can be done. The Canadian province of Alberta allows pharmacists to prescribe. And more recently, Idaho. While most states allow some sort of collaborative (dependent) prescribing, that is only a first step.”
Allowing pharmacists to independently prescribe will help populations who do not have a physician or can’t get access to a physician, the editorialists wrote. But changing state legislation would be a lengthy and complex effort.
Physician-Led BP Control Model ‘Seems to Fail Miserably’
Coauthor of the editorial, Florian Rader, MD, MSc, medical director of the Hypertension Center of Excellence at Cedars-Sinai Medical Center in Los Angeles, California, said in an interview that, currently, physician-led teams are the norm, “and that model seems to fail miserably.”
He offered several key reasons for that. In primary care, patients with hypertension often have other problems — they may have high cholesterol or diabetes. “They may have acute illnesses that bother them as well as hypertension that doesn’t bother them,” he said.
Physicians tend to find excuses not to increase or add BP medications, Rader said. “We tend then to blame ‘white coat effect’ or say ‘you’re just nervous today.’ ”
Pharmacists, comparatively, are more protocol driven, he said. “They essentially look at blood pressure and they have an algorithm in their mind. If the blood pressure hits the guideline-stated bar, start this medication. If it hits another bar, increase or add another medication.”
Rader said turf wars are also keeping physician-led teams from changing, fueled by fears that patients will seek care from pharmacists instead of physicians.
“I don’t think the pharmacists will steal a single patient,” Rader said. “If a physician had a healthcare partner like a pharmacist to optimize blood pressure, then [patients] come back to the physician with normalized BP on the right medications. I think it’s a total win-win. I think we just have to get over that.”
Pharmacist-led warfarin clinics are very well established, Rader said, “but for whatever reason, when it comes to blood pressure, physicians are a little bit more hesitant.”
Collaboration Yes, Independent No
Hypertension expert Donald J. DiPette, MD, Health Sciences Distinguished Professor in the Department of Internal Medicine at University of South Carolina, Columbia, said he completely agrees with Mills and colleagues’ conclusion. “Pharmacists and community health workers are most effective at leading BP intervention implementation and should be prioritized in future hypertension control efforts.”
The conclusion “is in line with the thinking of major organizations,” said DiPette, who helped develop the WHO’s most recent pharmacological treatment of hypertension guidelines. “WHO suggests that pharmacological treatment of hypertension can be provided by nonphysician professionals such as pharmacists and nurses as long as the following conditions are met: Proper training, prescribing authority, specific management protocols, and physician oversight.”
DiPette strongly believes BP control efforts should be supervised by a physician, but that could come in different ways. He suggested a collaborative but physician-supervised development of a protocol. Everyone contributes, but the physician signs off on it.
As for the Idaho example of independent practice for pharmacists, DiPette said he doesn’t think that will make a big difference in control rates. “That’s still not team-based care.”
Community Health Workers Key
He said he was also glad to see community healthcare workers emerge as the next-most-effective group after pharmacists to lead BP control teams. This is particularly important as BP control efforts globally need to consider the cultural experience of individual communities. “The community worker is on the ground, and can help overcome some of the cultural barriers,” he said.
“The key is to focus on team-based care and moving away from silo practice,” DiPette said.
Physicians, he said, often fall into “clinical or therapeutic inertia,” where BP is concerned. “We fail to titrate or add additional hypertensive medications even when they’re clearly indicated by the blood pressure. This is a problem not with the individual patient or the healthcare system, this is on us as physicians.”
Nonphysicians are more aligned with following protocols and guidelines, irrespective of the dynamics of what’s going on, he said.
And following protocols rigidly is a good thing for hypertension. “We’re not overtreating hypertension,” he emphasized. “We’re undertreating it.”
Reversing the trend on hypertension will take a sea change in medicine — changing institutions, systems, and individuals who have been doing things the same way for decades, he said.
“Our hypertension control rates are dismal,” DiPette said. “What’s more alarming is they’re going down. That’s the urgency. That’s the burning platform. We must strongly consider doing something different.”
Tsuyuki has received investigator-initiated arm’s length research grants from Merck, Pfizer, AstraZeneca, and Sanofi. He has been a speaker/consultant for Merck, Emergent BioSolutions, and Shoppers Drug Mart/Loblaw Companies Limited. Rader has been a consultant for Bristol Meyers Squibb, Cytokinetics, Idorsia, Medtronic, and ReCor Medical. Mills and coauthors reported no relevant financial relationships. DiPette declared no relevant financial relationships. He was part of a leadership team that developed WHO guidelines on hypertension.
A version of this article first appeared on Medscape.com.
Current efforts to control high blood pressure (BP) are failing in the United States and globally.
The first World Health Organization (WHO) global report on hypertension found that only 54% of adults with hypertension are diagnosed, 42% get treatment, and just 21% have their hypertension controlled.
In the United States, almost half (48%) of adults have high BP, defined as a systolic BP > 130 mm Hg, or a diastolic BP > 80 mm Hg, or are taking medication for high BP, according to the Centers for Disease Control and Prevention. Only about one in four adults (22.5%) with high BP have their BP under control.
High BP is a major risk factor for coronary heart disease, heart failure, and stroke, and the problem of controlling it is only getting worse. In 2024, the American Heart Association estimates that, “among adults, prevalence of hypertension will increase from 51.2% in 2020 to 61.0% in 2050.”
Pharmacists Most Effective
Though many factors contribute to hypertension, researchers have found that the kind of specialist leading the hypertension team may play a role in success. Currently, most BP control teams are led by physicians in primary care.
In a recent meta-analysis involving 100 randomized controlled trials and more than 90,000 patients in Circulation, Katherine T. Mills, PhD, School of Public Health, Tulane University, New Orleans, Louisiana, and colleagues found that, while all the groups studied who led BP control efforts were successful in reducing BP, pharmacist- and community health worker–led teams saw the biggest reductions.
Those groups’ efforts resulted in the greatest systolic BP drops: −7.3 mm Hg (pharmacists) and −7.1 mm Hg (community health workers). Groups led by nurses and physicians saw systolic changes of −3 and −2.4 mm Hg, respectively.
Similarly, pharmacist- and community health worker–led efforts saw the greatest diastolic BP reductions (−3.8 and −3.1 mm Hg), compared with nurse-led (−1.6) and physician-led (−1.2) efforts.
Reductions Enough to Cut Cardiovascular Disease Risk
The reduction numbers for pharmacists are clinically meaningful, Mills said in an interview. “It’s greater than a lot of what we see from individual lifestyle changes,” such as reducing sodium intake or increasing physical activity.
“It’s a big enough blood pressure change to have meaningful reduction in risk of cardiovascular disease,” she said.
This evidence that the leader of the team matters is particularly important because the treatment of hypertension is not in doubt. Something else is not working the way it should.
“We have basically all the scientific evidence we need in terms of what interventions work. But there’s a big gap between that and what’s actually being done in the real world,” she said.
Mills said she was not surprised that pharmacists got the best results “because so much of it has to do with titrating medications and finding the right kind of medications for each patient.”
Additionally, BP management and control falls right into pharmacists’ wheelhouse, Mills noted, including evaluating medication side effects and talking to patients about medication adherence.
Why Pharmacists May Be More Successful
In an accompanying editorial, Ross T. Tsuyuki, PharmD, with the EPICORE Centre, Division of Cardiology, University of Alberta in Edmonton, Canada, and coauthors said the Mills study provides further data to support pharmacists leading BP control efforts, but it’s not the data that have been keeping the model from changing. The barriers include turf wars and lack of legislative change.
The editorialists also said having pharmacist-led BP teams is only the first step. “We need pharmacists to independently prescribe,” they wrote.
“Since individual states govern the scope of practice of pharmacists,” the editorialists wrote, “we have the enormous task of changing regulations to allow pharmacists to independently prescribe for hypertension. But it can be done. The Canadian province of Alberta allows pharmacists to prescribe. And more recently, Idaho. While most states allow some sort of collaborative (dependent) prescribing, that is only a first step.”
Allowing pharmacists to independently prescribe will help populations who do not have a physician or can’t get access to a physician, the editorialists wrote. But changing state legislation would be a lengthy and complex effort.
Physician-Led BP Control Model ‘Seems to Fail Miserably’
Coauthor of the editorial, Florian Rader, MD, MSc, medical director of the Hypertension Center of Excellence at Cedars-Sinai Medical Center in Los Angeles, California, said in an interview that, currently, physician-led teams are the norm, “and that model seems to fail miserably.”
He offered several key reasons for that. In primary care, patients with hypertension often have other problems — they may have high cholesterol or diabetes. “They may have acute illnesses that bother them as well as hypertension that doesn’t bother them,” he said.
Physicians tend to find excuses not to increase or add BP medications, Rader said. “We tend then to blame ‘white coat effect’ or say ‘you’re just nervous today.’ ”
Pharmacists, comparatively, are more protocol driven, he said. “They essentially look at blood pressure and they have an algorithm in their mind. If the blood pressure hits the guideline-stated bar, start this medication. If it hits another bar, increase or add another medication.”
Rader said turf wars are also keeping physician-led teams from changing, fueled by fears that patients will seek care from pharmacists instead of physicians.
“I don’t think the pharmacists will steal a single patient,” Rader said. “If a physician had a healthcare partner like a pharmacist to optimize blood pressure, then [patients] come back to the physician with normalized BP on the right medications. I think it’s a total win-win. I think we just have to get over that.”
Pharmacist-led warfarin clinics are very well established, Rader said, “but for whatever reason, when it comes to blood pressure, physicians are a little bit more hesitant.”
Collaboration Yes, Independent No
Hypertension expert Donald J. DiPette, MD, Health Sciences Distinguished Professor in the Department of Internal Medicine at University of South Carolina, Columbia, said he completely agrees with Mills and colleagues’ conclusion. “Pharmacists and community health workers are most effective at leading BP intervention implementation and should be prioritized in future hypertension control efforts.”
The conclusion “is in line with the thinking of major organizations,” said DiPette, who helped develop the WHO’s most recent pharmacological treatment of hypertension guidelines. “WHO suggests that pharmacological treatment of hypertension can be provided by nonphysician professionals such as pharmacists and nurses as long as the following conditions are met: Proper training, prescribing authority, specific management protocols, and physician oversight.”
DiPette strongly believes BP control efforts should be supervised by a physician, but that could come in different ways. He suggested a collaborative but physician-supervised development of a protocol. Everyone contributes, but the physician signs off on it.
As for the Idaho example of independent practice for pharmacists, DiPette said he doesn’t think that will make a big difference in control rates. “That’s still not team-based care.”
Community Health Workers Key
He said he was also glad to see community healthcare workers emerge as the next-most-effective group after pharmacists to lead BP control teams. This is particularly important as BP control efforts globally need to consider the cultural experience of individual communities. “The community worker is on the ground, and can help overcome some of the cultural barriers,” he said.
“The key is to focus on team-based care and moving away from silo practice,” DiPette said.
Physicians, he said, often fall into “clinical or therapeutic inertia,” where BP is concerned. “We fail to titrate or add additional hypertensive medications even when they’re clearly indicated by the blood pressure. This is a problem not with the individual patient or the healthcare system, this is on us as physicians.”
Nonphysicians are more aligned with following protocols and guidelines, irrespective of the dynamics of what’s going on, he said.
And following protocols rigidly is a good thing for hypertension. “We’re not overtreating hypertension,” he emphasized. “We’re undertreating it.”
Reversing the trend on hypertension will take a sea change in medicine — changing institutions, systems, and individuals who have been doing things the same way for decades, he said.
“Our hypertension control rates are dismal,” DiPette said. “What’s more alarming is they’re going down. That’s the urgency. That’s the burning platform. We must strongly consider doing something different.”
Tsuyuki has received investigator-initiated arm’s length research grants from Merck, Pfizer, AstraZeneca, and Sanofi. He has been a speaker/consultant for Merck, Emergent BioSolutions, and Shoppers Drug Mart/Loblaw Companies Limited. Rader has been a consultant for Bristol Meyers Squibb, Cytokinetics, Idorsia, Medtronic, and ReCor Medical. Mills and coauthors reported no relevant financial relationships. DiPette declared no relevant financial relationships. He was part of a leadership team that developed WHO guidelines on hypertension.
A version of this article first appeared on Medscape.com.
Current efforts to control high blood pressure (BP) are failing in the United States and globally.
The first World Health Organization (WHO) global report on hypertension found that only 54% of adults with hypertension are diagnosed, 42% get treatment, and just 21% have their hypertension controlled.
In the United States, almost half (48%) of adults have high BP, defined as a systolic BP > 130 mm Hg, or a diastolic BP > 80 mm Hg, or are taking medication for high BP, according to the Centers for Disease Control and Prevention. Only about one in four adults (22.5%) with high BP have their BP under control.
High BP is a major risk factor for coronary heart disease, heart failure, and stroke, and the problem of controlling it is only getting worse. In 2024, the American Heart Association estimates that, “among adults, prevalence of hypertension will increase from 51.2% in 2020 to 61.0% in 2050.”
Pharmacists Most Effective
Though many factors contribute to hypertension, researchers have found that the kind of specialist leading the hypertension team may play a role in success. Currently, most BP control teams are led by physicians in primary care.
In a recent meta-analysis involving 100 randomized controlled trials and more than 90,000 patients in Circulation, Katherine T. Mills, PhD, School of Public Health, Tulane University, New Orleans, Louisiana, and colleagues found that, while all the groups studied who led BP control efforts were successful in reducing BP, pharmacist- and community health worker–led teams saw the biggest reductions.
Those groups’ efforts resulted in the greatest systolic BP drops: −7.3 mm Hg (pharmacists) and −7.1 mm Hg (community health workers). Groups led by nurses and physicians saw systolic changes of −3 and −2.4 mm Hg, respectively.
Similarly, pharmacist- and community health worker–led efforts saw the greatest diastolic BP reductions (−3.8 and −3.1 mm Hg), compared with nurse-led (−1.6) and physician-led (−1.2) efforts.
Reductions Enough to Cut Cardiovascular Disease Risk
The reduction numbers for pharmacists are clinically meaningful, Mills said in an interview. “It’s greater than a lot of what we see from individual lifestyle changes,” such as reducing sodium intake or increasing physical activity.
“It’s a big enough blood pressure change to have meaningful reduction in risk of cardiovascular disease,” she said.
This evidence that the leader of the team matters is particularly important because the treatment of hypertension is not in doubt. Something else is not working the way it should.
“We have basically all the scientific evidence we need in terms of what interventions work. But there’s a big gap between that and what’s actually being done in the real world,” she said.
Mills said she was not surprised that pharmacists got the best results “because so much of it has to do with titrating medications and finding the right kind of medications for each patient.”
Additionally, BP management and control falls right into pharmacists’ wheelhouse, Mills noted, including evaluating medication side effects and talking to patients about medication adherence.
Why Pharmacists May Be More Successful
In an accompanying editorial, Ross T. Tsuyuki, PharmD, with the EPICORE Centre, Division of Cardiology, University of Alberta in Edmonton, Canada, and coauthors said the Mills study provides further data to support pharmacists leading BP control efforts, but it’s not the data that have been keeping the model from changing. The barriers include turf wars and lack of legislative change.
The editorialists also said having pharmacist-led BP teams is only the first step. “We need pharmacists to independently prescribe,” they wrote.
“Since individual states govern the scope of practice of pharmacists,” the editorialists wrote, “we have the enormous task of changing regulations to allow pharmacists to independently prescribe for hypertension. But it can be done. The Canadian province of Alberta allows pharmacists to prescribe. And more recently, Idaho. While most states allow some sort of collaborative (dependent) prescribing, that is only a first step.”
Allowing pharmacists to independently prescribe will help populations who do not have a physician or can’t get access to a physician, the editorialists wrote. But changing state legislation would be a lengthy and complex effort.
Physician-Led BP Control Model ‘Seems to Fail Miserably’
Coauthor of the editorial, Florian Rader, MD, MSc, medical director of the Hypertension Center of Excellence at Cedars-Sinai Medical Center in Los Angeles, California, said in an interview that, currently, physician-led teams are the norm, “and that model seems to fail miserably.”
He offered several key reasons for that. In primary care, patients with hypertension often have other problems — they may have high cholesterol or diabetes. “They may have acute illnesses that bother them as well as hypertension that doesn’t bother them,” he said.
Physicians tend to find excuses not to increase or add BP medications, Rader said. “We tend then to blame ‘white coat effect’ or say ‘you’re just nervous today.’ ”
Pharmacists, comparatively, are more protocol driven, he said. “They essentially look at blood pressure and they have an algorithm in their mind. If the blood pressure hits the guideline-stated bar, start this medication. If it hits another bar, increase or add another medication.”
Rader said turf wars are also keeping physician-led teams from changing, fueled by fears that patients will seek care from pharmacists instead of physicians.
“I don’t think the pharmacists will steal a single patient,” Rader said. “If a physician had a healthcare partner like a pharmacist to optimize blood pressure, then [patients] come back to the physician with normalized BP on the right medications. I think it’s a total win-win. I think we just have to get over that.”
Pharmacist-led warfarin clinics are very well established, Rader said, “but for whatever reason, when it comes to blood pressure, physicians are a little bit more hesitant.”
Collaboration Yes, Independent No
Hypertension expert Donald J. DiPette, MD, Health Sciences Distinguished Professor in the Department of Internal Medicine at University of South Carolina, Columbia, said he completely agrees with Mills and colleagues’ conclusion. “Pharmacists and community health workers are most effective at leading BP intervention implementation and should be prioritized in future hypertension control efforts.”
The conclusion “is in line with the thinking of major organizations,” said DiPette, who helped develop the WHO’s most recent pharmacological treatment of hypertension guidelines. “WHO suggests that pharmacological treatment of hypertension can be provided by nonphysician professionals such as pharmacists and nurses as long as the following conditions are met: Proper training, prescribing authority, specific management protocols, and physician oversight.”
DiPette strongly believes BP control efforts should be supervised by a physician, but that could come in different ways. He suggested a collaborative but physician-supervised development of a protocol. Everyone contributes, but the physician signs off on it.
As for the Idaho example of independent practice for pharmacists, DiPette said he doesn’t think that will make a big difference in control rates. “That’s still not team-based care.”
Community Health Workers Key
He said he was also glad to see community healthcare workers emerge as the next-most-effective group after pharmacists to lead BP control teams. This is particularly important as BP control efforts globally need to consider the cultural experience of individual communities. “The community worker is on the ground, and can help overcome some of the cultural barriers,” he said.
“The key is to focus on team-based care and moving away from silo practice,” DiPette said.
Physicians, he said, often fall into “clinical or therapeutic inertia,” where BP is concerned. “We fail to titrate or add additional hypertensive medications even when they’re clearly indicated by the blood pressure. This is a problem not with the individual patient or the healthcare system, this is on us as physicians.”
Nonphysicians are more aligned with following protocols and guidelines, irrespective of the dynamics of what’s going on, he said.
And following protocols rigidly is a good thing for hypertension. “We’re not overtreating hypertension,” he emphasized. “We’re undertreating it.”
Reversing the trend on hypertension will take a sea change in medicine — changing institutions, systems, and individuals who have been doing things the same way for decades, he said.
“Our hypertension control rates are dismal,” DiPette said. “What’s more alarming is they’re going down. That’s the urgency. That’s the burning platform. We must strongly consider doing something different.”
Tsuyuki has received investigator-initiated arm’s length research grants from Merck, Pfizer, AstraZeneca, and Sanofi. He has been a speaker/consultant for Merck, Emergent BioSolutions, and Shoppers Drug Mart/Loblaw Companies Limited. Rader has been a consultant for Bristol Meyers Squibb, Cytokinetics, Idorsia, Medtronic, and ReCor Medical. Mills and coauthors reported no relevant financial relationships. DiPette declared no relevant financial relationships. He was part of a leadership team that developed WHO guidelines on hypertension.
A version of this article first appeared on Medscape.com.
The Pediatrician’s Role in Suicide Prevention
When she was 5 years old, Katherine Edson, LCSW, tried to end her life by drowning herself. “I was enduring severe physical and sexual abuse, and it had become unbearable,” she said. “I waded into a lake, knowing there was a point when it would become too deep and I’d go under.”
As she was walking toward the deeper water, it occurred to her that if she died, she wouldn’t be able to eat Rice Krispies again. “I thought, ‘no more Snap, Crackle, and Pop’ — the three little mascots on the cereal box — and I felt sad,” said Edson, a New York–based retired therapist. “But I still kept walking.”
A man on the shore saw her disappear under the water and pulled her out. “I remember vomiting a lot of water and I remember that the man had tattoos, but I don’t remember how I felt to be alive. I was just numb.”
Edson thinks there were clues her pediatrician missed. “We lived in a small Southern town. Everyone knew my parents were alcoholics. I was very dissociated and withdrawn in general and during pediatric visits. My affect broadcasted that something was wrong, but no one asked if I was okay.”
She acknowledged that professionals in those days “weren’t tuned in to mental health issues in kids. At least there’s more awareness today and hopefully more training — especially since it seems like more kids are trying to end their lives today than when I was growing up.”
Alarming Statistics
According to the American Academy of Pediatrics (AAP), suicide is the second leading cause of death for people aged 10-24 years. Data from Children’s Hospital Association’s Pediatric Health Information System revealed that suicide attempts, ideation, and self-injury have become the most common mental health conditions seen in the emergency departments (EDs) of children’s hospitals, with a 166% increase in ED visits for suicide attempts in children aged 5-18 years, between 2016 and 2022.
Psychiatrist Helen Egger, MD, chief medical officer and co-founder of Little Otter, a specialty pediatric and whole family digital mental health company, recently coauthored a report analyzing data on 1434 children who completed a screening session and comprehensive diagnostic assessment at Little Otter from May 2023 to February 2024 (n = 1016 children aged 8-14 years and n = 418 aged 3-7 years).
Almost one fifth of the older children presented with current positive suicide risk (suicidal ideation and/or behavior in the last month), while 6% of the younger age group presented with current suicide risk. The youngest was 5 years old.
Points of Contact
“It’s known that most children who die by suicide had a recent visit with a health professional — a pediatrician or child mental health professional. It’s unlikely that the child was fine and then, a few weeks later, stopped being fine. The likelihood is that the child wasn’t fine during that visit, but the clinician didn’t ask about mental health,” Egger said.
Christine Crawford, MD, MPH, associate medical director of the National Alliance on Mental Illness (NAMI), said that “When you’re working with kids, anything can come up. Be prepared to navigate the conversation. You can never predict who the patient will feel most comfortable disclosing these thoughts to.”
Pediatricians are the physicians most likely to be seen by children, and it’s important for pediatricians to inquire about a child’s mood, especially during child visits, according to Crawford, author of the book You Are Not Alone for Parents and Caregivers: The NAMI Guide to Navigating Your Child’s Mental Health.
Donald E. Greydanus, MD, professor and founding chair, Department of Pediatric and Adolescent Medicine, Homer Stryker MD School of Medicine, Western Michigan University, Kalamazoo, Michigan, said many fellow pediatricians have said the highly compressed exam doesn’t allow enough time to ask questions. “But pediatricians must find a way to make time,” he said. “Asking about depression and potential suicidality is top priority and can help keep your patients alive.”
Some pediatricians have told him, “I’m not prepared to provide counseling.” But “your role isn’t to provide counseling, just to open the conversation, offer hope, and direct the youngster to resources that can help.”
Don’t Be Afraid to Ask
According to the AAP, all children aged 12 years or older should be screened for suicidal risk, and children aged 8-11 years should be screened “when clinically indicated.” AAP also recommends annual screening for depression in children aged 12 years or older. However, Egger thinks that screening for depression should start sooner.
It can be tempting to screen by merely giving a youngster a form to fill out in the waiting room, but Greydanus strongly advises against this approach. “The important thing is having rapport with the child, being in the same room together. You can ask some simple questions. ‘How are you doing? How are things at school? How are things with your family?’”
“When you’re screening for depression and have a kid who’s talking about sadness or low mood for more than 2 weeks and endorsing other symptoms, such as problems with sleep or appetite, difficulty concentrating, anhedonia, losing interest in things they’d usually enjoy, feeling they’re a burden to others, hopelessness about the future, being unable to function the way they used to — that person meets criteria for depression and you should have a high suspicion and concern about potential suicide,” said Crawford, assistant professor of psychiatry, Boston University School of Medicine.
She suggested probing further and being direct. “It sounds like you’ve been having a tough time. You talk about being sad. I wonder if you’re feeling so sad that you might not want to be alive anymore.” Some healthcare providers “tiptoe around when it comes to suicide, but it’s better to be direct and communicate the question in simple, plain language: ‘Have you ever had thoughts about hurting or killing yourself, that life is no longer worth living, or life would be easier for your family if you weren’t alive?’”
It’s a common myth that asking about depression or suicidality will “plant a seed” or “put ideas in people’s heads,” potentially leading to suicidality. “What we know to be true is that asking about suicide doesn’t put lives at risk. In fact, the contrary is true,” according to Crawford. Several studies have refuted this myth.
Two screening tools that might be helpful in ascertaining the presence of depression and suicidality are the PHQ-9 modified for Adolescents and the four-question Ask Suicide-Screening Questions.
Probe for More Details
If a child or adolescent affirms suicidal ideation, it’s important to ask if they have a plan, Crawford advised. “If they say, ‘yes,’ don’t run out of the office or shut down the conversation by picking up the phone and calling the closest child psychiatrist. We want kids to open up as much as possible when they’ve already opened up a little. So continue the conversation.”
If a child has a plan, the risk for following through on that plan is “high,” Crawford emphasized. “You want the maximum amount of information at your fingertips because this will equip you to navigate the next step in getting the child help.”
The suicide plan may not be realistic and, if carried out, might not actually end in death, especially in younger children. “A 6-year-old might say, ‘I’m gonna drink a whole bottle of apple juice and my belly will explode.’ Or ‘I’ll take 10 extra vitamins.’ The objective lethality of the plan doesn’t matter in that moment. What matters is that the child believes it’s going to work, and it provides a window into how depressed that child is.”
Greydanus added that it’s important to understand what might be going on in the child’s life. Could there be abuse in the family? Is the child being bullied? Bullying can take place at school or online, he noted. The overall risk for suicidal thoughts is elevated for youth who are involved in bullying, whether they’re the bully or the one being bullied.
Kirk Smalley, president and co-founder of Stand for the Silent, an organization designed to bring awareness about the devastating effects of bullying, agreed that pediatricians a should ask children if they’re being bullied. “Sometimes, kids will open up to someone who isn’t a parent or a teacher, who might be seen as ‘too close’ to the situation,” Smalley said.
“Let them know you’re a trusted adult they can confide in and you’re willing to help them navigate this — and then follow through,” advised Smalley, whose 11-year-old son died by suicide after being subjected to bullying.
Painting a Complete Picture
Crawford advises clinicians to “look at the whole picture and piece it together.”
For example, “if the child is functioning, going to school, maintaining relationships with other people, and not experiencing symptoms of depression but discloses the desire to kill him/herself, understand the context.” Sometimes, adolescents can be impulsive. Decision-making “can be driven by emotion.” The teen may have experienced emotional distress, such as “conflict with a peer, arguments with a parent, or romantic heartbreak. She might say, ‘I’m going to kill myself if I ever see him holding hands with another girl.’”
In the setting of an acute stressor, such as a breakup, the child might not need a higher level of care such as hospitalization. “But for non-psychiatry providers, it’s unclear if the child might act on it, so it’s important to have the child evaluated; talk to collateral supports, such as parents, teachers, or a therapist if they have one; and see what makes sense for that specific child.”
She also recommended “getting a sense if the kid is future-oriented in thinking. If they’re talking about an upcoming concert this weekend, or wanting to get to basketball practice, that’s reassuring. It suggests the likelihood of following through [on suicide] is low.”
And assess coping strategies. “You can say, ‘I see you’re really going through a lot. I worry that these thoughts will come up in school. What do you think you’d do in the moment if these thoughts come up?’ If there’s a coping strategy — for example, ‘I’d talk to my friend during lunch’ — that’s also reassuring,” Crawford said.
Of course, that doesn’t mean the statement should be ignored or dismissed. Rather, it informs the next preventive steps and how intensive the level of care should be.
Next Steps: Involving the Family, Getting Help
It’s particularly concerning if the child is unable to identify strategies other than suicide, said Crawford. “You can say, ‘I’m concerned because it’s highly likely that you’ll run into this guy and I wouldn’t want you to die. You have so much to live for.’”
Then, you can ask if it’s okay to bring in the parent or caregiver to talk about what the child just revealed. “If the kid says no — especially a teen — you can respond, ‘I hear what you’re saying, but I actually do have to bring your parent in because of your safety and we can discuss together how to keep you safe.’”
In advance, Crawford tells the patient what she plans to share with the parent. “That way, we’re on the same page and the kid has a sense of agency about how the conversation with the parent will go.” If the teen doesn’t want certain information revealed, “you can ask, ‘What would you leave out, and why?’ This lends itself to a helpful conversation about what the child is thinking about.”
Once the provider has received the green light, it’s time to bring the parent into the room. “Especially in the primary care or pediatric setting, the parent is often shocked, worried, and caught off-guard,” Crawford said.
“You can start by thanking the patient for being open and honest. Then you can tell the parent, ‘Your daughter shared she’s been having some difficult emotions and experiences, and she’s thought of ending her life because she doesn’t know how to cope. I wanted to talk to you about this because it’s important to look at resources we can connect her to and effective coping strategies.’”
Further interventions can include referring the patient to a child psychiatrist or therapist, or both. “Have a list of referrals readily available,” Greydanus advised. If you suspect or if the child reveals abuse, you’re a mandated reporter and need to inform Child Protective Services (CPS). “But don’t stop there,” he warned. “Make sure the child is indeed getting help through CPS and appropriate intervention has been taken regarding the abuse and potential suicide attempt.” Or you may send the child to the ED, where ED physicians are “trained in what to do if they suspect abuse. But make sure that when you ‘throw the ball,’ there’s someone who can ‘catch’ it and accept responsibility for the child’s safety.”
Crawford noted that many primary care settings — especially in under-resourced areas — lack child psychiatrists or therapists. “You need to know what’s feasible in the community you’re practicing in,” she advised. “Be aware of the local crisis line — 988 — and mental health resources in the school and community. There are often school psychologists, social workers, or counselors who can become involved.”
Greydanus emphasized that it’s critical to assess for the presence of firearms in the home and address it with the parents. “If a child is sad or angry and gets impulsive, it’s amazingly common for them to get their hands in a firearm and use it.”
As previously reported, pediatricians and other healthcare providers have a valuable role to play in screening parents for firearm ownership and offering counseling on safe storage practices, according to research presented on September 28 at the AAP 2024 National Conference.
Sometimes, Even the Best Efforts Aren’t Successful
“Suicide is complicated, and parents or doctors can take all the ‘right’ steps to get counseling for the child — hospitalization, medication, and support — and children might still take their lives,” said Ronnie Susan Walker, MS, LCPC, founder and executive director of Alliance of Hope for Suicide Loss Survivors. The organization was launched as a “postvention campaign” 7 years ago to provide support to survivors of suicide loss, who are themselves a high-risk population for suicide.
Walker alluded to the concept of a “ suicide trance” — a term coined by Richard Heckler, PhD, in his book Waking Up, Alive. This trance “is a state of mind and body that receives only the kind of input that reinforces the pain and corroborates the person’s conviction that the only way out is through death,” Heckler wrote.
Walker, whose stepson died by suicide, said physicians and other healthcare professionals who have lost a patient to suicide “should focus on postvention — finding support from other professionals and managing their own grief and guilt.”
It’s natural to feel guilt and second-guess yourself, Greydanus said. “You question whether you missed something or could have done more, so acknowledge that even with the best care and intentions, some suicides aren’t preventable,” he said.
Walker recommends reaching out to the family. “When I lost my stepson, his doctor came to the funeral and wrote us a very meaningful note. That meant so much to us.”
Greydanus agreed it’s appropriate for the clinician to offer comfort to the family “if he or she feels it necessary or feels moved to do so.” However, he cautioned, there’s “often a fear of malpractice charges that may interfere in certain cases.”
Egger added that records should always be “very detailed,” with clear documentation of how you interacted with the child and the rationale behind your interventions. “I’m not a legal expert, but I would always err on the side of connecting with family and sharing grief and compassion. My experience with physician-patient relationships is that the more connected, transparent, and empathetic they are, the better the outcome will be for everyone.”
Losing a patient to suicide is traumatic, so give yourself time to grieve, Egger advised. “Unfortunately, this is an experience that almost everyone in the field will likely go through at some point. Reach out for professional counseling or peer support.”
Physicians who have lost a patient to suicide may turn to an online forum, the Coalition of Clinician Survivors, designed to create a safe anonymous space for discussion, education, testimonials, and one-on-one support.
Greydanus emphasized that the most important role in working with suicidal youngsters is to provide hope. “Yes, you can’t help everyone, but you can help most of them. That’s why you’re there.”
Greydanus, Crawford, Egger, Edson, Smalley, and Walker reported no financial conflicts of interest.
A version of this article appeared on Medscape.com.
When she was 5 years old, Katherine Edson, LCSW, tried to end her life by drowning herself. “I was enduring severe physical and sexual abuse, and it had become unbearable,” she said. “I waded into a lake, knowing there was a point when it would become too deep and I’d go under.”
As she was walking toward the deeper water, it occurred to her that if she died, she wouldn’t be able to eat Rice Krispies again. “I thought, ‘no more Snap, Crackle, and Pop’ — the three little mascots on the cereal box — and I felt sad,” said Edson, a New York–based retired therapist. “But I still kept walking.”
A man on the shore saw her disappear under the water and pulled her out. “I remember vomiting a lot of water and I remember that the man had tattoos, but I don’t remember how I felt to be alive. I was just numb.”
Edson thinks there were clues her pediatrician missed. “We lived in a small Southern town. Everyone knew my parents were alcoholics. I was very dissociated and withdrawn in general and during pediatric visits. My affect broadcasted that something was wrong, but no one asked if I was okay.”
She acknowledged that professionals in those days “weren’t tuned in to mental health issues in kids. At least there’s more awareness today and hopefully more training — especially since it seems like more kids are trying to end their lives today than when I was growing up.”
Alarming Statistics
According to the American Academy of Pediatrics (AAP), suicide is the second leading cause of death for people aged 10-24 years. Data from Children’s Hospital Association’s Pediatric Health Information System revealed that suicide attempts, ideation, and self-injury have become the most common mental health conditions seen in the emergency departments (EDs) of children’s hospitals, with a 166% increase in ED visits for suicide attempts in children aged 5-18 years, between 2016 and 2022.
Psychiatrist Helen Egger, MD, chief medical officer and co-founder of Little Otter, a specialty pediatric and whole family digital mental health company, recently coauthored a report analyzing data on 1434 children who completed a screening session and comprehensive diagnostic assessment at Little Otter from May 2023 to February 2024 (n = 1016 children aged 8-14 years and n = 418 aged 3-7 years).
Almost one fifth of the older children presented with current positive suicide risk (suicidal ideation and/or behavior in the last month), while 6% of the younger age group presented with current suicide risk. The youngest was 5 years old.
Points of Contact
“It’s known that most children who die by suicide had a recent visit with a health professional — a pediatrician or child mental health professional. It’s unlikely that the child was fine and then, a few weeks later, stopped being fine. The likelihood is that the child wasn’t fine during that visit, but the clinician didn’t ask about mental health,” Egger said.
Christine Crawford, MD, MPH, associate medical director of the National Alliance on Mental Illness (NAMI), said that “When you’re working with kids, anything can come up. Be prepared to navigate the conversation. You can never predict who the patient will feel most comfortable disclosing these thoughts to.”
Pediatricians are the physicians most likely to be seen by children, and it’s important for pediatricians to inquire about a child’s mood, especially during child visits, according to Crawford, author of the book You Are Not Alone for Parents and Caregivers: The NAMI Guide to Navigating Your Child’s Mental Health.
Donald E. Greydanus, MD, professor and founding chair, Department of Pediatric and Adolescent Medicine, Homer Stryker MD School of Medicine, Western Michigan University, Kalamazoo, Michigan, said many fellow pediatricians have said the highly compressed exam doesn’t allow enough time to ask questions. “But pediatricians must find a way to make time,” he said. “Asking about depression and potential suicidality is top priority and can help keep your patients alive.”
Some pediatricians have told him, “I’m not prepared to provide counseling.” But “your role isn’t to provide counseling, just to open the conversation, offer hope, and direct the youngster to resources that can help.”
Don’t Be Afraid to Ask
According to the AAP, all children aged 12 years or older should be screened for suicidal risk, and children aged 8-11 years should be screened “when clinically indicated.” AAP also recommends annual screening for depression in children aged 12 years or older. However, Egger thinks that screening for depression should start sooner.
It can be tempting to screen by merely giving a youngster a form to fill out in the waiting room, but Greydanus strongly advises against this approach. “The important thing is having rapport with the child, being in the same room together. You can ask some simple questions. ‘How are you doing? How are things at school? How are things with your family?’”
“When you’re screening for depression and have a kid who’s talking about sadness or low mood for more than 2 weeks and endorsing other symptoms, such as problems with sleep or appetite, difficulty concentrating, anhedonia, losing interest in things they’d usually enjoy, feeling they’re a burden to others, hopelessness about the future, being unable to function the way they used to — that person meets criteria for depression and you should have a high suspicion and concern about potential suicide,” said Crawford, assistant professor of psychiatry, Boston University School of Medicine.
She suggested probing further and being direct. “It sounds like you’ve been having a tough time. You talk about being sad. I wonder if you’re feeling so sad that you might not want to be alive anymore.” Some healthcare providers “tiptoe around when it comes to suicide, but it’s better to be direct and communicate the question in simple, plain language: ‘Have you ever had thoughts about hurting or killing yourself, that life is no longer worth living, or life would be easier for your family if you weren’t alive?’”
It’s a common myth that asking about depression or suicidality will “plant a seed” or “put ideas in people’s heads,” potentially leading to suicidality. “What we know to be true is that asking about suicide doesn’t put lives at risk. In fact, the contrary is true,” according to Crawford. Several studies have refuted this myth.
Two screening tools that might be helpful in ascertaining the presence of depression and suicidality are the PHQ-9 modified for Adolescents and the four-question Ask Suicide-Screening Questions.
Probe for More Details
If a child or adolescent affirms suicidal ideation, it’s important to ask if they have a plan, Crawford advised. “If they say, ‘yes,’ don’t run out of the office or shut down the conversation by picking up the phone and calling the closest child psychiatrist. We want kids to open up as much as possible when they’ve already opened up a little. So continue the conversation.”
If a child has a plan, the risk for following through on that plan is “high,” Crawford emphasized. “You want the maximum amount of information at your fingertips because this will equip you to navigate the next step in getting the child help.”
The suicide plan may not be realistic and, if carried out, might not actually end in death, especially in younger children. “A 6-year-old might say, ‘I’m gonna drink a whole bottle of apple juice and my belly will explode.’ Or ‘I’ll take 10 extra vitamins.’ The objective lethality of the plan doesn’t matter in that moment. What matters is that the child believes it’s going to work, and it provides a window into how depressed that child is.”
Greydanus added that it’s important to understand what might be going on in the child’s life. Could there be abuse in the family? Is the child being bullied? Bullying can take place at school or online, he noted. The overall risk for suicidal thoughts is elevated for youth who are involved in bullying, whether they’re the bully or the one being bullied.
Kirk Smalley, president and co-founder of Stand for the Silent, an organization designed to bring awareness about the devastating effects of bullying, agreed that pediatricians a should ask children if they’re being bullied. “Sometimes, kids will open up to someone who isn’t a parent or a teacher, who might be seen as ‘too close’ to the situation,” Smalley said.
“Let them know you’re a trusted adult they can confide in and you’re willing to help them navigate this — and then follow through,” advised Smalley, whose 11-year-old son died by suicide after being subjected to bullying.
Painting a Complete Picture
Crawford advises clinicians to “look at the whole picture and piece it together.”
For example, “if the child is functioning, going to school, maintaining relationships with other people, and not experiencing symptoms of depression but discloses the desire to kill him/herself, understand the context.” Sometimes, adolescents can be impulsive. Decision-making “can be driven by emotion.” The teen may have experienced emotional distress, such as “conflict with a peer, arguments with a parent, or romantic heartbreak. She might say, ‘I’m going to kill myself if I ever see him holding hands with another girl.’”
In the setting of an acute stressor, such as a breakup, the child might not need a higher level of care such as hospitalization. “But for non-psychiatry providers, it’s unclear if the child might act on it, so it’s important to have the child evaluated; talk to collateral supports, such as parents, teachers, or a therapist if they have one; and see what makes sense for that specific child.”
She also recommended “getting a sense if the kid is future-oriented in thinking. If they’re talking about an upcoming concert this weekend, or wanting to get to basketball practice, that’s reassuring. It suggests the likelihood of following through [on suicide] is low.”
And assess coping strategies. “You can say, ‘I see you’re really going through a lot. I worry that these thoughts will come up in school. What do you think you’d do in the moment if these thoughts come up?’ If there’s a coping strategy — for example, ‘I’d talk to my friend during lunch’ — that’s also reassuring,” Crawford said.
Of course, that doesn’t mean the statement should be ignored or dismissed. Rather, it informs the next preventive steps and how intensive the level of care should be.
Next Steps: Involving the Family, Getting Help
It’s particularly concerning if the child is unable to identify strategies other than suicide, said Crawford. “You can say, ‘I’m concerned because it’s highly likely that you’ll run into this guy and I wouldn’t want you to die. You have so much to live for.’”
Then, you can ask if it’s okay to bring in the parent or caregiver to talk about what the child just revealed. “If the kid says no — especially a teen — you can respond, ‘I hear what you’re saying, but I actually do have to bring your parent in because of your safety and we can discuss together how to keep you safe.’”
In advance, Crawford tells the patient what she plans to share with the parent. “That way, we’re on the same page and the kid has a sense of agency about how the conversation with the parent will go.” If the teen doesn’t want certain information revealed, “you can ask, ‘What would you leave out, and why?’ This lends itself to a helpful conversation about what the child is thinking about.”
Once the provider has received the green light, it’s time to bring the parent into the room. “Especially in the primary care or pediatric setting, the parent is often shocked, worried, and caught off-guard,” Crawford said.
“You can start by thanking the patient for being open and honest. Then you can tell the parent, ‘Your daughter shared she’s been having some difficult emotions and experiences, and she’s thought of ending her life because she doesn’t know how to cope. I wanted to talk to you about this because it’s important to look at resources we can connect her to and effective coping strategies.’”
Further interventions can include referring the patient to a child psychiatrist or therapist, or both. “Have a list of referrals readily available,” Greydanus advised. If you suspect or if the child reveals abuse, you’re a mandated reporter and need to inform Child Protective Services (CPS). “But don’t stop there,” he warned. “Make sure the child is indeed getting help through CPS and appropriate intervention has been taken regarding the abuse and potential suicide attempt.” Or you may send the child to the ED, where ED physicians are “trained in what to do if they suspect abuse. But make sure that when you ‘throw the ball,’ there’s someone who can ‘catch’ it and accept responsibility for the child’s safety.”
Crawford noted that many primary care settings — especially in under-resourced areas — lack child psychiatrists or therapists. “You need to know what’s feasible in the community you’re practicing in,” she advised. “Be aware of the local crisis line — 988 — and mental health resources in the school and community. There are often school psychologists, social workers, or counselors who can become involved.”
Greydanus emphasized that it’s critical to assess for the presence of firearms in the home and address it with the parents. “If a child is sad or angry and gets impulsive, it’s amazingly common for them to get their hands in a firearm and use it.”
As previously reported, pediatricians and other healthcare providers have a valuable role to play in screening parents for firearm ownership and offering counseling on safe storage practices, according to research presented on September 28 at the AAP 2024 National Conference.
Sometimes, Even the Best Efforts Aren’t Successful
“Suicide is complicated, and parents or doctors can take all the ‘right’ steps to get counseling for the child — hospitalization, medication, and support — and children might still take their lives,” said Ronnie Susan Walker, MS, LCPC, founder and executive director of Alliance of Hope for Suicide Loss Survivors. The organization was launched as a “postvention campaign” 7 years ago to provide support to survivors of suicide loss, who are themselves a high-risk population for suicide.
Walker alluded to the concept of a “ suicide trance” — a term coined by Richard Heckler, PhD, in his book Waking Up, Alive. This trance “is a state of mind and body that receives only the kind of input that reinforces the pain and corroborates the person’s conviction that the only way out is through death,” Heckler wrote.
Walker, whose stepson died by suicide, said physicians and other healthcare professionals who have lost a patient to suicide “should focus on postvention — finding support from other professionals and managing their own grief and guilt.”
It’s natural to feel guilt and second-guess yourself, Greydanus said. “You question whether you missed something or could have done more, so acknowledge that even with the best care and intentions, some suicides aren’t preventable,” he said.
Walker recommends reaching out to the family. “When I lost my stepson, his doctor came to the funeral and wrote us a very meaningful note. That meant so much to us.”
Greydanus agreed it’s appropriate for the clinician to offer comfort to the family “if he or she feels it necessary or feels moved to do so.” However, he cautioned, there’s “often a fear of malpractice charges that may interfere in certain cases.”
Egger added that records should always be “very detailed,” with clear documentation of how you interacted with the child and the rationale behind your interventions. “I’m not a legal expert, but I would always err on the side of connecting with family and sharing grief and compassion. My experience with physician-patient relationships is that the more connected, transparent, and empathetic they are, the better the outcome will be for everyone.”
Losing a patient to suicide is traumatic, so give yourself time to grieve, Egger advised. “Unfortunately, this is an experience that almost everyone in the field will likely go through at some point. Reach out for professional counseling or peer support.”
Physicians who have lost a patient to suicide may turn to an online forum, the Coalition of Clinician Survivors, designed to create a safe anonymous space for discussion, education, testimonials, and one-on-one support.
Greydanus emphasized that the most important role in working with suicidal youngsters is to provide hope. “Yes, you can’t help everyone, but you can help most of them. That’s why you’re there.”
Greydanus, Crawford, Egger, Edson, Smalley, and Walker reported no financial conflicts of interest.
A version of this article appeared on Medscape.com.
When she was 5 years old, Katherine Edson, LCSW, tried to end her life by drowning herself. “I was enduring severe physical and sexual abuse, and it had become unbearable,” she said. “I waded into a lake, knowing there was a point when it would become too deep and I’d go under.”
As she was walking toward the deeper water, it occurred to her that if she died, she wouldn’t be able to eat Rice Krispies again. “I thought, ‘no more Snap, Crackle, and Pop’ — the three little mascots on the cereal box — and I felt sad,” said Edson, a New York–based retired therapist. “But I still kept walking.”
A man on the shore saw her disappear under the water and pulled her out. “I remember vomiting a lot of water and I remember that the man had tattoos, but I don’t remember how I felt to be alive. I was just numb.”
Edson thinks there were clues her pediatrician missed. “We lived in a small Southern town. Everyone knew my parents were alcoholics. I was very dissociated and withdrawn in general and during pediatric visits. My affect broadcasted that something was wrong, but no one asked if I was okay.”
She acknowledged that professionals in those days “weren’t tuned in to mental health issues in kids. At least there’s more awareness today and hopefully more training — especially since it seems like more kids are trying to end their lives today than when I was growing up.”
Alarming Statistics
According to the American Academy of Pediatrics (AAP), suicide is the second leading cause of death for people aged 10-24 years. Data from Children’s Hospital Association’s Pediatric Health Information System revealed that suicide attempts, ideation, and self-injury have become the most common mental health conditions seen in the emergency departments (EDs) of children’s hospitals, with a 166% increase in ED visits for suicide attempts in children aged 5-18 years, between 2016 and 2022.
Psychiatrist Helen Egger, MD, chief medical officer and co-founder of Little Otter, a specialty pediatric and whole family digital mental health company, recently coauthored a report analyzing data on 1434 children who completed a screening session and comprehensive diagnostic assessment at Little Otter from May 2023 to February 2024 (n = 1016 children aged 8-14 years and n = 418 aged 3-7 years).
Almost one fifth of the older children presented with current positive suicide risk (suicidal ideation and/or behavior in the last month), while 6% of the younger age group presented with current suicide risk. The youngest was 5 years old.
Points of Contact
“It’s known that most children who die by suicide had a recent visit with a health professional — a pediatrician or child mental health professional. It’s unlikely that the child was fine and then, a few weeks later, stopped being fine. The likelihood is that the child wasn’t fine during that visit, but the clinician didn’t ask about mental health,” Egger said.
Christine Crawford, MD, MPH, associate medical director of the National Alliance on Mental Illness (NAMI), said that “When you’re working with kids, anything can come up. Be prepared to navigate the conversation. You can never predict who the patient will feel most comfortable disclosing these thoughts to.”
Pediatricians are the physicians most likely to be seen by children, and it’s important for pediatricians to inquire about a child’s mood, especially during child visits, according to Crawford, author of the book You Are Not Alone for Parents and Caregivers: The NAMI Guide to Navigating Your Child’s Mental Health.
Donald E. Greydanus, MD, professor and founding chair, Department of Pediatric and Adolescent Medicine, Homer Stryker MD School of Medicine, Western Michigan University, Kalamazoo, Michigan, said many fellow pediatricians have said the highly compressed exam doesn’t allow enough time to ask questions. “But pediatricians must find a way to make time,” he said. “Asking about depression and potential suicidality is top priority and can help keep your patients alive.”
Some pediatricians have told him, “I’m not prepared to provide counseling.” But “your role isn’t to provide counseling, just to open the conversation, offer hope, and direct the youngster to resources that can help.”
Don’t Be Afraid to Ask
According to the AAP, all children aged 12 years or older should be screened for suicidal risk, and children aged 8-11 years should be screened “when clinically indicated.” AAP also recommends annual screening for depression in children aged 12 years or older. However, Egger thinks that screening for depression should start sooner.
It can be tempting to screen by merely giving a youngster a form to fill out in the waiting room, but Greydanus strongly advises against this approach. “The important thing is having rapport with the child, being in the same room together. You can ask some simple questions. ‘How are you doing? How are things at school? How are things with your family?’”
“When you’re screening for depression and have a kid who’s talking about sadness or low mood for more than 2 weeks and endorsing other symptoms, such as problems with sleep or appetite, difficulty concentrating, anhedonia, losing interest in things they’d usually enjoy, feeling they’re a burden to others, hopelessness about the future, being unable to function the way they used to — that person meets criteria for depression and you should have a high suspicion and concern about potential suicide,” said Crawford, assistant professor of psychiatry, Boston University School of Medicine.
She suggested probing further and being direct. “It sounds like you’ve been having a tough time. You talk about being sad. I wonder if you’re feeling so sad that you might not want to be alive anymore.” Some healthcare providers “tiptoe around when it comes to suicide, but it’s better to be direct and communicate the question in simple, plain language: ‘Have you ever had thoughts about hurting or killing yourself, that life is no longer worth living, or life would be easier for your family if you weren’t alive?’”
It’s a common myth that asking about depression or suicidality will “plant a seed” or “put ideas in people’s heads,” potentially leading to suicidality. “What we know to be true is that asking about suicide doesn’t put lives at risk. In fact, the contrary is true,” according to Crawford. Several studies have refuted this myth.
Two screening tools that might be helpful in ascertaining the presence of depression and suicidality are the PHQ-9 modified for Adolescents and the four-question Ask Suicide-Screening Questions.
Probe for More Details
If a child or adolescent affirms suicidal ideation, it’s important to ask if they have a plan, Crawford advised. “If they say, ‘yes,’ don’t run out of the office or shut down the conversation by picking up the phone and calling the closest child psychiatrist. We want kids to open up as much as possible when they’ve already opened up a little. So continue the conversation.”
If a child has a plan, the risk for following through on that plan is “high,” Crawford emphasized. “You want the maximum amount of information at your fingertips because this will equip you to navigate the next step in getting the child help.”
The suicide plan may not be realistic and, if carried out, might not actually end in death, especially in younger children. “A 6-year-old might say, ‘I’m gonna drink a whole bottle of apple juice and my belly will explode.’ Or ‘I’ll take 10 extra vitamins.’ The objective lethality of the plan doesn’t matter in that moment. What matters is that the child believes it’s going to work, and it provides a window into how depressed that child is.”
Greydanus added that it’s important to understand what might be going on in the child’s life. Could there be abuse in the family? Is the child being bullied? Bullying can take place at school or online, he noted. The overall risk for suicidal thoughts is elevated for youth who are involved in bullying, whether they’re the bully or the one being bullied.
Kirk Smalley, president and co-founder of Stand for the Silent, an organization designed to bring awareness about the devastating effects of bullying, agreed that pediatricians a should ask children if they’re being bullied. “Sometimes, kids will open up to someone who isn’t a parent or a teacher, who might be seen as ‘too close’ to the situation,” Smalley said.
“Let them know you’re a trusted adult they can confide in and you’re willing to help them navigate this — and then follow through,” advised Smalley, whose 11-year-old son died by suicide after being subjected to bullying.
Painting a Complete Picture
Crawford advises clinicians to “look at the whole picture and piece it together.”
For example, “if the child is functioning, going to school, maintaining relationships with other people, and not experiencing symptoms of depression but discloses the desire to kill him/herself, understand the context.” Sometimes, adolescents can be impulsive. Decision-making “can be driven by emotion.” The teen may have experienced emotional distress, such as “conflict with a peer, arguments with a parent, or romantic heartbreak. She might say, ‘I’m going to kill myself if I ever see him holding hands with another girl.’”
In the setting of an acute stressor, such as a breakup, the child might not need a higher level of care such as hospitalization. “But for non-psychiatry providers, it’s unclear if the child might act on it, so it’s important to have the child evaluated; talk to collateral supports, such as parents, teachers, or a therapist if they have one; and see what makes sense for that specific child.”
She also recommended “getting a sense if the kid is future-oriented in thinking. If they’re talking about an upcoming concert this weekend, or wanting to get to basketball practice, that’s reassuring. It suggests the likelihood of following through [on suicide] is low.”
And assess coping strategies. “You can say, ‘I see you’re really going through a lot. I worry that these thoughts will come up in school. What do you think you’d do in the moment if these thoughts come up?’ If there’s a coping strategy — for example, ‘I’d talk to my friend during lunch’ — that’s also reassuring,” Crawford said.
Of course, that doesn’t mean the statement should be ignored or dismissed. Rather, it informs the next preventive steps and how intensive the level of care should be.
Next Steps: Involving the Family, Getting Help
It’s particularly concerning if the child is unable to identify strategies other than suicide, said Crawford. “You can say, ‘I’m concerned because it’s highly likely that you’ll run into this guy and I wouldn’t want you to die. You have so much to live for.’”
Then, you can ask if it’s okay to bring in the parent or caregiver to talk about what the child just revealed. “If the kid says no — especially a teen — you can respond, ‘I hear what you’re saying, but I actually do have to bring your parent in because of your safety and we can discuss together how to keep you safe.’”
In advance, Crawford tells the patient what she plans to share with the parent. “That way, we’re on the same page and the kid has a sense of agency about how the conversation with the parent will go.” If the teen doesn’t want certain information revealed, “you can ask, ‘What would you leave out, and why?’ This lends itself to a helpful conversation about what the child is thinking about.”
Once the provider has received the green light, it’s time to bring the parent into the room. “Especially in the primary care or pediatric setting, the parent is often shocked, worried, and caught off-guard,” Crawford said.
“You can start by thanking the patient for being open and honest. Then you can tell the parent, ‘Your daughter shared she’s been having some difficult emotions and experiences, and she’s thought of ending her life because she doesn’t know how to cope. I wanted to talk to you about this because it’s important to look at resources we can connect her to and effective coping strategies.’”
Further interventions can include referring the patient to a child psychiatrist or therapist, or both. “Have a list of referrals readily available,” Greydanus advised. If you suspect or if the child reveals abuse, you’re a mandated reporter and need to inform Child Protective Services (CPS). “But don’t stop there,” he warned. “Make sure the child is indeed getting help through CPS and appropriate intervention has been taken regarding the abuse and potential suicide attempt.” Or you may send the child to the ED, where ED physicians are “trained in what to do if they suspect abuse. But make sure that when you ‘throw the ball,’ there’s someone who can ‘catch’ it and accept responsibility for the child’s safety.”
Crawford noted that many primary care settings — especially in under-resourced areas — lack child psychiatrists or therapists. “You need to know what’s feasible in the community you’re practicing in,” she advised. “Be aware of the local crisis line — 988 — and mental health resources in the school and community. There are often school psychologists, social workers, or counselors who can become involved.”
Greydanus emphasized that it’s critical to assess for the presence of firearms in the home and address it with the parents. “If a child is sad or angry and gets impulsive, it’s amazingly common for them to get their hands in a firearm and use it.”
As previously reported, pediatricians and other healthcare providers have a valuable role to play in screening parents for firearm ownership and offering counseling on safe storage practices, according to research presented on September 28 at the AAP 2024 National Conference.
Sometimes, Even the Best Efforts Aren’t Successful
“Suicide is complicated, and parents or doctors can take all the ‘right’ steps to get counseling for the child — hospitalization, medication, and support — and children might still take their lives,” said Ronnie Susan Walker, MS, LCPC, founder and executive director of Alliance of Hope for Suicide Loss Survivors. The organization was launched as a “postvention campaign” 7 years ago to provide support to survivors of suicide loss, who are themselves a high-risk population for suicide.
Walker alluded to the concept of a “ suicide trance” — a term coined by Richard Heckler, PhD, in his book Waking Up, Alive. This trance “is a state of mind and body that receives only the kind of input that reinforces the pain and corroborates the person’s conviction that the only way out is through death,” Heckler wrote.
Walker, whose stepson died by suicide, said physicians and other healthcare professionals who have lost a patient to suicide “should focus on postvention — finding support from other professionals and managing their own grief and guilt.”
It’s natural to feel guilt and second-guess yourself, Greydanus said. “You question whether you missed something or could have done more, so acknowledge that even with the best care and intentions, some suicides aren’t preventable,” he said.
Walker recommends reaching out to the family. “When I lost my stepson, his doctor came to the funeral and wrote us a very meaningful note. That meant so much to us.”
Greydanus agreed it’s appropriate for the clinician to offer comfort to the family “if he or she feels it necessary or feels moved to do so.” However, he cautioned, there’s “often a fear of malpractice charges that may interfere in certain cases.”
Egger added that records should always be “very detailed,” with clear documentation of how you interacted with the child and the rationale behind your interventions. “I’m not a legal expert, but I would always err on the side of connecting with family and sharing grief and compassion. My experience with physician-patient relationships is that the more connected, transparent, and empathetic they are, the better the outcome will be for everyone.”
Losing a patient to suicide is traumatic, so give yourself time to grieve, Egger advised. “Unfortunately, this is an experience that almost everyone in the field will likely go through at some point. Reach out for professional counseling or peer support.”
Physicians who have lost a patient to suicide may turn to an online forum, the Coalition of Clinician Survivors, designed to create a safe anonymous space for discussion, education, testimonials, and one-on-one support.
Greydanus emphasized that the most important role in working with suicidal youngsters is to provide hope. “Yes, you can’t help everyone, but you can help most of them. That’s why you’re there.”
Greydanus, Crawford, Egger, Edson, Smalley, and Walker reported no financial conflicts of interest.
A version of this article appeared on Medscape.com.
Should the Body Roundness Index Replace BMI?
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s 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.
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s 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.
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s 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.
Thyroid Cancer Overdiagnosis Continues Despite Cautions
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
Starting Mammograms at Age 40: Will Women Benefit?
Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74.
The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.
For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women.
But is this recommendation to screen earlier a change for the better?
Opinions vary.
USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.
“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year.
However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.
The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women.
More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.
However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.
Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime.
The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.
“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”
Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better.
Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily.
Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary.
But several experts not involved in the USPSTF recommendations agree with the change.
The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.
Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.”
“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.
One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.
“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.
The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.
There is one place where experts seem to align: the importance of educating patients about their personal risk.
The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50.
“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote.
For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization.
“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”
Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25.
“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added.
Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
A version of this article appeared on Medscape.com.
Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74.
The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.
For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women.
But is this recommendation to screen earlier a change for the better?
Opinions vary.
USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.
“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year.
However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.
The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women.
More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.
However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.
Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime.
The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.
“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”
Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better.
Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily.
Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary.
But several experts not involved in the USPSTF recommendations agree with the change.
The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.
Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.”
“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.
One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.
“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.
The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.
There is one place where experts seem to align: the importance of educating patients about their personal risk.
The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50.
“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote.
For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization.
“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”
Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25.
“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added.
Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
A version of this article appeared on Medscape.com.
Last April, the US Preventive Services Task Force (USPSTF) revised its breast cancer screening guidelines to recommend average-risk women start their screening mammograms at age 40, instead of age 50, and continue every other year until age 74.
The USPSTF’s recent recommendations align with those from major organizations, including the National Comprehensive Cancer Network and the American College of Radiology. The latest update comes from the American College of Obstetricians and Gynecologists (ACOG), which recommended a start age of 40 and continued screening either annually or every 2 years.
For USPSTF, the decision to recommend the earlier screening age, instead of keeping the choice an individualized one, was largely driven by the steady rise in breast cancer diagnoses among women in their 40s, alongside evidence that Black women are more likely to get breast cancer younger and die from the disease compared with White women.
But is this recommendation to screen earlier a change for the better?
Opinions vary.
USPSTF member John Wong, MD, chief of clinical decision making and a primary care physician at Tufts Medical Center in Boston, believes the new recommendation is the right move.
“It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women and there is even greater potential benefit for Black women, who are much more likely to die from breast cancer,” Wong told Medscape last year.
However, in a recent Viewpoint in JAMA Internal Medicine, experts from the University of California San Francisco expressed their reservations about shifting the recommended screening age a decade earlier.
The trio — Karla Kerlikowske, MD, Laura Esserman, MD, and Jeffrey Tice, MD — called the new recommendations “surprising” given the lack of new randomized control trial data to support the change as well as data that show breast cancer deaths have been decreasing among women, including younger women.
More specifically, breast cancer deaths for women under 50 have decreased from 5.9 to 3.9 per 100,000 individuals between 2000 and 2020 — a decline that can likely be attributed to better treatments rather than increased screening effectiveness, the Viewpoint authors said.
However, moving the screening age earlier would not markedly improve survival for most women, the authors argued. According to USPSTF modeling, starting mammograms at age 40 instead of 50 could avert only 1.3 additional breast cancer deaths per 1000 women screened biennially and 1.8 additional breast cancer deaths among Black women.
Starting screening at 40, however, does come with an array of potential harms. These include 65 more benign biopsies per 1000 women screened, 1 in 2 women with a false-positive mammography result (503 per 1000), and 1 in 500 women with an over-diagnosed breast cancer, meaning the cancer would not have become clinically evident in their lifetime.
The use of digital breast tomosynthesis can slightly reduce the number of false-positives and benign biopsies compared to older mammography techniques, but these small improvements did not sway the overall pro-con assessment for the Viewpoint authors.
“False-positive results require additional imaging and are associated with anxiety for patients,” the authors noted. “Women who have benign biopsies may experience the potential adverse effects of biopsies, such as bleeding, infection, and scarring unnecessarily; and over-diagnosis may lead to unnecessary treatment.”
Kenneth Lin, MD, MPH, family physician and associate director of the Lancaster General Hospital Family Medicine Residency in Pennsylvania, agreed that starting mammograms at age 40 is not a change for the better.
Lin and colleagues conducted an analysis based on data from the USPSTF’s 2016 breast cancer screening report that similarly found 1 additional breast cancer death prevented per 1000 women screened starting at 40 vs 50, at a cost of 576 more false-positive results, 67 more benign breast biopsies, and 2 women diagnosed and treated unnecessarily.
Overall, “there is no compelling evidence to change our clinical approach to breast cancer screening for women in their 40s: individual decision-making based on patient preferences and values,” Lin wrote in a recent Medscape commentary.
But several experts not involved in the USPSTF recommendations agree with the change.
The updated recommendation to begin mammograms at age 40 for women at average risk “aligns with accumulating data suggesting that earlier and more frequent screening can save more lives, and is widely seen as a positive step,” said Lisa Abramson, MD, a radiologist specializing in breast imaging with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York City.
Melissa Fana, MD, a breast surgical oncologist at NYU Langone Health, agreed that the revised recommendation is justified and “will undoubtedly save lives.”
“The recent change in the screening recommendation was meant to be inclusive, and provide women, particularly women aged 40 to 49 the opportunity to screen with mammography,” Fana said.
One major argument in favor of earlier screening is that it will help address racial inequities in breast cancer diagnoses, treatment, and deaths. Despite a 5% lower incidence of breast cancer, Black women are more likely to be diagnosed with distant-stage cancer or more aggressive breast cancer subtypes, such as triple-negative, compared with White women, and are more likely to die from breast cancer.
“We hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” said Cherie C. Hill, MD, FACOG, an ob.gyn. at Emory Healthcare in Atlanta, who coauthored the recent ACOG recommendations.
The Viewpoint authors Kerlikowske, Esserman and Tice agreed that Black women may benefit more from earlier screening. However, earlier screening does not address the underlying disparities in treatment and follow-up care for Black women, and it is unclear whether screening alone will help improve breast cancer mortality rates for Black women, the authors noted.
There is one place where experts seem to align: the importance of educating patients about their personal risk.
The Viewpoint authors favor a risk-based approach to help women decide whether to start screening before age 50.
“Engaging women in informed decision-making based on their invasive and advanced breast cancer risk would be a patient-centered approach toward tailored screening, informing when to consider starting screening and how often to screen,” the experts wrote.
For a woman to truly make an educated decision on whether she would like to screen or wait after age 40, she would at least need to know what her specific lifetime risk of developing breast cancer is, not the average risk is for American women in general, Fana told this news organization.
“Risk assessment calculators are widely available and include factors such as family history and reproductive history, and this information can evolve over time and affect lifetime risk,” Fana noted. But “some women just do not get this information.”
Abramson explained that ob.gyns. and primary care physicians will likely play a larger role in the early assessment of breast cancer risk, including discussions about genetic testing and personal risk factors starting as early as age 25.
“For clinicians, the emphasis may be on educating patients about their individual risk, ensuring timely mammograms, and referring higher-risk individuals for further testing or consultations with specialists,” Abramson added.
Esserman reported being a Blue Cross Medical Advisory Panel member, an uncompensated board member of Quantum Leap Healthcare Collaborative, which funds the I-SPY trial through the University of California, San Francisco, and having an investigator-initiated trial for high-risk ductal carcinoma in situ (DCIS) funded through UCSF by Moderna for a DCIS phase 1 study. Tice and Kerlikowske reported receiving grants from the National Cancer Institute outside the submitted work. Abramson and Fana have no relevant disclosures.
A version of this article appeared on Medscape.com.
Will Psychedelics Break the Major Depression Logjam?
With tens of millions of Euros in the offing, researchers across the European Union have eagerly taken up the gauntlet to find novel interventions for difficult-to-treat mental health and pain conditions. Their target is psychedelics, including classic compounds like psilocybin and atypical ones like ketamine and MDMA. Some of these still carry a stigma as party drugs and spiritual gateways to holotropic experiences.
Twelve groups make up the European College of Neuropsychopharmacology’s psychedelic research network. Along with several affiliates, the groups span nine countries (Denmark, Sweden, Finland, Switzerland, Germany, the Netherlands, the Czech Republic, Greece, and the United Kingdom) and are focused on the use of psychedelic compounds as potential treatments for psychiatric conditions like treatment-resistant depression, addiction, attention-deficit/hyperactivity disorder, anorexia, and obsessive-compulsive disorder.
One of the largest endeavors is PsyPal, a 4-year, randomized controlled trial investigating the potential of psilocybin for treating psychological distress in palliative care patients with life-limiting conditions. PsyPal is the first multisite clinical trial funded by the European Union to explore psychedelic-assisted therapy.
At PsyPal’s helm is Robert Schoevers, MD, PhD, professor of psychiatry and Department Head at University Medical Center Groningen (UMCG), Groningen, the Netherlands, a major hub for psychedelic research.
Schoevers is a bit of a pioneer who said he entered psychedelic research somewhat reluctantly. A decade ago, a colleague showed him a few papers on ketamine and depression. Because UMCG has a large population of patients with treatment-resistant depression, he agreed to do a pilot study. Since then, he has put together an interdisciplinary team of 25 researchers, published numerous papers, and currently has seven studies, including PsyPal, in various stages of progress.
Schoevers is also building a large national consortium that aims to investigate and, if shown effective, implement novel psychiatry treatments much more rapidly and efficiently than current drug development and approval processes, which can take 12 years or longer. He has just secured millions in government funding to start this process.
Next year, Schoevers and his team will decide to test either MDMA for posttraumatic stress disorder (PTSD) or psilocybin for depression in a large clinical trial, with the aim of getting a treatment as near to formal registration as possible. This will involve working with the European Medicines Agency and its Dutch counterpart, talking to experts who are familiar with the US Food and Drug Administration’s rejection of Lykos Therapeutics’ MDMA treatment for PTSD, and working directly with patients through the National Patient Alliance. The team is also talking to insurers and pharma companies.
The ultimate goal is to “see if we can build a platform in the Netherlands that would have a European perspective, serve as a point of entry for researchers with good ideas, and [attract] public funding as well as companies who have interesting compounds we think would be worthwhile to study,” Schoevers said.
His multiple endeavors emphasize a transdisciplinary and transdiagnostic approach he has been honing for decades. He and his colleagues are investigating the clinical, psychological, and neurobiological parallels between different treatment- resistant conditions and seeking to understand how contextual factors might influence patients, experiences, and outcomes.
Connecting the Dots
Jens H. van Dalfsen, PhD, a postdoctoral researcher in biological psychiatry, is the principal investigator of another UMCG group looking into the neurobiological mechanisms of major depressive disorder and treatment-resistant depression. His team’s strategy entails an elaborate coordination between the preclinical and clinical research settings.
For example, Sarah Massetti, a PhD candidate in biological psychiatry, is using blood samples collected in clinical trials to investigate the molecular mechanisms underpinning the neuroplasticity and immune-modulating effects produced by psychedelic compounds.
Another line of research spearheaded by Rutger Boesjes, a PhD candidate in biological psychiatry, is exploring the interactions between drugs like ketamine and the circadian system and how they might relate to antidepressant responses in animal models. It could be that the timing of administration of these drugs is relevant, he explained.
The Patient Factor
How psychedelics work and in whom is a big question for the UMCG team and across the research landscape.
“When researchers and the general public talk about psychedelics, they frequently refer to how they promote synaptic plasticity and new connections in the brain,” said van Dalfsen. “But traditional compounds also do that. So the ultimate question that we’ve been exploring is whether findings reflect an actual pharmacological effect or if expectancy also plays a role. In other words: How can we explain why psychedelics might or might not be effective in treatment-resistant patients?” he explained.
This is where the connection to the clinical experience becomes paramount and Joost Breeksema, PhD, comes in.
Breeksema divides his time between UMCG research and his role as executive director and co-founder of the Open Foundation, a nonprofit dedicated to advancing scientific psychedelic research. The work he’s doing outside the university is helping to frame the investigations of the wider group.
So far he has conducted two qualitative studies.
One was an off-label study in which patients with treatment-resistant depression were administered esketamine.
The other was a randomized clinical trial in which participants were blinded to a single 10- or 25-mg dose of psilocybin versus a 1-mg psilocybin microdose placebo that is too small to invoke any effects.
A key insight was the degree to which participants were unprepared for the intensity of their experiences, especially with regards to ketamine. Breeksema said the sessions might not have been so intense or negative for some participants had they been informed beforehand to expect the drugs could provoke “quite overwhelming experiences” and had they been accompanied by an experienced guide providing reassurance and support.
The format for the psilocybin trial met part of this criteria. Participants received a micro (placebo), medium, or high dose in a single session accompanied by two trained therapists. They then engaged in two sessions afterward to process their experiences. A single psilocybin experience appeared to be not enough or too much depending on the dose they were assigned and if they had prior experience with the compound.
Trial participants also felt they needed more help making sense of the experience. “This is a common and important theme,” said Breeksema. “Think about it. If you’ve been depressed for 10, 15 years and … you uncover something and break through something that’s been stuck, you need to process it.”
Jeanine Kamphuis, PhD, a psychiatrist and senior researcher at UMCG and one of the trial study co-authors, explained that they want to find a way to identify who will be too overwhelmed by these experiences if the dose should be adjusted or if some time needs to pass between dosing sessions. They also want to spend more time preparing patients for these sessions.
She emphasized that the studies have provided a reality check. “These are not wonder pills or wonder experiences. And in these types of patients, they’re not intended for a personal growth experience,” she said. “You have a patient who is sitting in front of you who seeks therapy and relief from very severe mood complaints, and the suffering is high,” she said, adding that expectancy bias further complicates patient participation and, likely, outcomes.
The Challenges
For all the potential and opportunity that psychedelics may hold for treatment, UMCG’s work has underscored some challenges.
The field of psychedelic research is characterized by methodological issues, explained van Dalfsen, such as blinding, expectancy, and overestimation of treatment effects. When looking at efficacy, “Is it the compound or the expectancy and promise? This is why it’s important to study how the drugs differ from each other in their biological effects and why they are or are not effective,” he said.
The team has also experienced issues with trial recruitment.
Martijn Godschalk, MD, a PhD candidate in psychiatry, has been addressing this problem while working on RESET-TRD, a phase 3, randomized controlled trial comparing an oral esketamine drink with electroconvulsive therapy in patients with treatment-resistant depression.
He’s been coordinating with local university hospitals, general hospitals, and municipal healthcare clinics to meet inclusion criteria and ensure the trial has enough power to demonstrate effectiveness. In turn, these sites are able to participate in a trial they wouldn’t normally be involved in due to lack of resources.
But Godschalk said he was concerned that many patients have gotten wind of the hype surrounding psychedelic treatments within psychiatry — a factor that has contributed to recruitment challenges. “There are a lot of patients who are interested in the non-registered drug and don’t necessarily have an interest in the other [control] arm,” he said.
Despite the challenges, the classic psychedelics such as MDMA and psilocybin “seem to catalyze a psychological process that may be harder to get with regular psychotherapies,” said Schoevers.
He remains cautious, noting there are still unanswered questions, such as who are the best candidates for these drugs and whether they might cause harm in certain patients while benefiting others. “I do think that this is the first time in 20 or 30 years that there is a group of potential treatments that would really make a difference.”
Schoevers received grants and other funding from The Netherlands Organisation for Health Research & Development, Horizon 2020, Horizon 2023, the National Institute of Mental Health (USA), UMCG, Stichting tot Steun VCVGZ, Nationaal programma Groningen, Healthcare Innovation Funds, Janssen Pharmaceuticals, Novartis, Compass Pathways, Clexio Biosciences, and GH research.
A version of this article appeared on Medscape.com.
With tens of millions of Euros in the offing, researchers across the European Union have eagerly taken up the gauntlet to find novel interventions for difficult-to-treat mental health and pain conditions. Their target is psychedelics, including classic compounds like psilocybin and atypical ones like ketamine and MDMA. Some of these still carry a stigma as party drugs and spiritual gateways to holotropic experiences.
Twelve groups make up the European College of Neuropsychopharmacology’s psychedelic research network. Along with several affiliates, the groups span nine countries (Denmark, Sweden, Finland, Switzerland, Germany, the Netherlands, the Czech Republic, Greece, and the United Kingdom) and are focused on the use of psychedelic compounds as potential treatments for psychiatric conditions like treatment-resistant depression, addiction, attention-deficit/hyperactivity disorder, anorexia, and obsessive-compulsive disorder.
One of the largest endeavors is PsyPal, a 4-year, randomized controlled trial investigating the potential of psilocybin for treating psychological distress in palliative care patients with life-limiting conditions. PsyPal is the first multisite clinical trial funded by the European Union to explore psychedelic-assisted therapy.
At PsyPal’s helm is Robert Schoevers, MD, PhD, professor of psychiatry and Department Head at University Medical Center Groningen (UMCG), Groningen, the Netherlands, a major hub for psychedelic research.
Schoevers is a bit of a pioneer who said he entered psychedelic research somewhat reluctantly. A decade ago, a colleague showed him a few papers on ketamine and depression. Because UMCG has a large population of patients with treatment-resistant depression, he agreed to do a pilot study. Since then, he has put together an interdisciplinary team of 25 researchers, published numerous papers, and currently has seven studies, including PsyPal, in various stages of progress.
Schoevers is also building a large national consortium that aims to investigate and, if shown effective, implement novel psychiatry treatments much more rapidly and efficiently than current drug development and approval processes, which can take 12 years or longer. He has just secured millions in government funding to start this process.
Next year, Schoevers and his team will decide to test either MDMA for posttraumatic stress disorder (PTSD) or psilocybin for depression in a large clinical trial, with the aim of getting a treatment as near to formal registration as possible. This will involve working with the European Medicines Agency and its Dutch counterpart, talking to experts who are familiar with the US Food and Drug Administration’s rejection of Lykos Therapeutics’ MDMA treatment for PTSD, and working directly with patients through the National Patient Alliance. The team is also talking to insurers and pharma companies.
The ultimate goal is to “see if we can build a platform in the Netherlands that would have a European perspective, serve as a point of entry for researchers with good ideas, and [attract] public funding as well as companies who have interesting compounds we think would be worthwhile to study,” Schoevers said.
His multiple endeavors emphasize a transdisciplinary and transdiagnostic approach he has been honing for decades. He and his colleagues are investigating the clinical, psychological, and neurobiological parallels between different treatment- resistant conditions and seeking to understand how contextual factors might influence patients, experiences, and outcomes.
Connecting the Dots
Jens H. van Dalfsen, PhD, a postdoctoral researcher in biological psychiatry, is the principal investigator of another UMCG group looking into the neurobiological mechanisms of major depressive disorder and treatment-resistant depression. His team’s strategy entails an elaborate coordination between the preclinical and clinical research settings.
For example, Sarah Massetti, a PhD candidate in biological psychiatry, is using blood samples collected in clinical trials to investigate the molecular mechanisms underpinning the neuroplasticity and immune-modulating effects produced by psychedelic compounds.
Another line of research spearheaded by Rutger Boesjes, a PhD candidate in biological psychiatry, is exploring the interactions between drugs like ketamine and the circadian system and how they might relate to antidepressant responses in animal models. It could be that the timing of administration of these drugs is relevant, he explained.
The Patient Factor
How psychedelics work and in whom is a big question for the UMCG team and across the research landscape.
“When researchers and the general public talk about psychedelics, they frequently refer to how they promote synaptic plasticity and new connections in the brain,” said van Dalfsen. “But traditional compounds also do that. So the ultimate question that we’ve been exploring is whether findings reflect an actual pharmacological effect or if expectancy also plays a role. In other words: How can we explain why psychedelics might or might not be effective in treatment-resistant patients?” he explained.
This is where the connection to the clinical experience becomes paramount and Joost Breeksema, PhD, comes in.
Breeksema divides his time between UMCG research and his role as executive director and co-founder of the Open Foundation, a nonprofit dedicated to advancing scientific psychedelic research. The work he’s doing outside the university is helping to frame the investigations of the wider group.
So far he has conducted two qualitative studies.
One was an off-label study in which patients with treatment-resistant depression were administered esketamine.
The other was a randomized clinical trial in which participants were blinded to a single 10- or 25-mg dose of psilocybin versus a 1-mg psilocybin microdose placebo that is too small to invoke any effects.
A key insight was the degree to which participants were unprepared for the intensity of their experiences, especially with regards to ketamine. Breeksema said the sessions might not have been so intense or negative for some participants had they been informed beforehand to expect the drugs could provoke “quite overwhelming experiences” and had they been accompanied by an experienced guide providing reassurance and support.
The format for the psilocybin trial met part of this criteria. Participants received a micro (placebo), medium, or high dose in a single session accompanied by two trained therapists. They then engaged in two sessions afterward to process their experiences. A single psilocybin experience appeared to be not enough or too much depending on the dose they were assigned and if they had prior experience with the compound.
Trial participants also felt they needed more help making sense of the experience. “This is a common and important theme,” said Breeksema. “Think about it. If you’ve been depressed for 10, 15 years and … you uncover something and break through something that’s been stuck, you need to process it.”
Jeanine Kamphuis, PhD, a psychiatrist and senior researcher at UMCG and one of the trial study co-authors, explained that they want to find a way to identify who will be too overwhelmed by these experiences if the dose should be adjusted or if some time needs to pass between dosing sessions. They also want to spend more time preparing patients for these sessions.
She emphasized that the studies have provided a reality check. “These are not wonder pills or wonder experiences. And in these types of patients, they’re not intended for a personal growth experience,” she said. “You have a patient who is sitting in front of you who seeks therapy and relief from very severe mood complaints, and the suffering is high,” she said, adding that expectancy bias further complicates patient participation and, likely, outcomes.
The Challenges
For all the potential and opportunity that psychedelics may hold for treatment, UMCG’s work has underscored some challenges.
The field of psychedelic research is characterized by methodological issues, explained van Dalfsen, such as blinding, expectancy, and overestimation of treatment effects. When looking at efficacy, “Is it the compound or the expectancy and promise? This is why it’s important to study how the drugs differ from each other in their biological effects and why they are or are not effective,” he said.
The team has also experienced issues with trial recruitment.
Martijn Godschalk, MD, a PhD candidate in psychiatry, has been addressing this problem while working on RESET-TRD, a phase 3, randomized controlled trial comparing an oral esketamine drink with electroconvulsive therapy in patients with treatment-resistant depression.
He’s been coordinating with local university hospitals, general hospitals, and municipal healthcare clinics to meet inclusion criteria and ensure the trial has enough power to demonstrate effectiveness. In turn, these sites are able to participate in a trial they wouldn’t normally be involved in due to lack of resources.
But Godschalk said he was concerned that many patients have gotten wind of the hype surrounding psychedelic treatments within psychiatry — a factor that has contributed to recruitment challenges. “There are a lot of patients who are interested in the non-registered drug and don’t necessarily have an interest in the other [control] arm,” he said.
Despite the challenges, the classic psychedelics such as MDMA and psilocybin “seem to catalyze a psychological process that may be harder to get with regular psychotherapies,” said Schoevers.
He remains cautious, noting there are still unanswered questions, such as who are the best candidates for these drugs and whether they might cause harm in certain patients while benefiting others. “I do think that this is the first time in 20 or 30 years that there is a group of potential treatments that would really make a difference.”
Schoevers received grants and other funding from The Netherlands Organisation for Health Research & Development, Horizon 2020, Horizon 2023, the National Institute of Mental Health (USA), UMCG, Stichting tot Steun VCVGZ, Nationaal programma Groningen, Healthcare Innovation Funds, Janssen Pharmaceuticals, Novartis, Compass Pathways, Clexio Biosciences, and GH research.
A version of this article appeared on Medscape.com.
With tens of millions of Euros in the offing, researchers across the European Union have eagerly taken up the gauntlet to find novel interventions for difficult-to-treat mental health and pain conditions. Their target is psychedelics, including classic compounds like psilocybin and atypical ones like ketamine and MDMA. Some of these still carry a stigma as party drugs and spiritual gateways to holotropic experiences.
Twelve groups make up the European College of Neuropsychopharmacology’s psychedelic research network. Along with several affiliates, the groups span nine countries (Denmark, Sweden, Finland, Switzerland, Germany, the Netherlands, the Czech Republic, Greece, and the United Kingdom) and are focused on the use of psychedelic compounds as potential treatments for psychiatric conditions like treatment-resistant depression, addiction, attention-deficit/hyperactivity disorder, anorexia, and obsessive-compulsive disorder.
One of the largest endeavors is PsyPal, a 4-year, randomized controlled trial investigating the potential of psilocybin for treating psychological distress in palliative care patients with life-limiting conditions. PsyPal is the first multisite clinical trial funded by the European Union to explore psychedelic-assisted therapy.
At PsyPal’s helm is Robert Schoevers, MD, PhD, professor of psychiatry and Department Head at University Medical Center Groningen (UMCG), Groningen, the Netherlands, a major hub for psychedelic research.
Schoevers is a bit of a pioneer who said he entered psychedelic research somewhat reluctantly. A decade ago, a colleague showed him a few papers on ketamine and depression. Because UMCG has a large population of patients with treatment-resistant depression, he agreed to do a pilot study. Since then, he has put together an interdisciplinary team of 25 researchers, published numerous papers, and currently has seven studies, including PsyPal, in various stages of progress.
Schoevers is also building a large national consortium that aims to investigate and, if shown effective, implement novel psychiatry treatments much more rapidly and efficiently than current drug development and approval processes, which can take 12 years or longer. He has just secured millions in government funding to start this process.
Next year, Schoevers and his team will decide to test either MDMA for posttraumatic stress disorder (PTSD) or psilocybin for depression in a large clinical trial, with the aim of getting a treatment as near to formal registration as possible. This will involve working with the European Medicines Agency and its Dutch counterpart, talking to experts who are familiar with the US Food and Drug Administration’s rejection of Lykos Therapeutics’ MDMA treatment for PTSD, and working directly with patients through the National Patient Alliance. The team is also talking to insurers and pharma companies.
The ultimate goal is to “see if we can build a platform in the Netherlands that would have a European perspective, serve as a point of entry for researchers with good ideas, and [attract] public funding as well as companies who have interesting compounds we think would be worthwhile to study,” Schoevers said.
His multiple endeavors emphasize a transdisciplinary and transdiagnostic approach he has been honing for decades. He and his colleagues are investigating the clinical, psychological, and neurobiological parallels between different treatment- resistant conditions and seeking to understand how contextual factors might influence patients, experiences, and outcomes.
Connecting the Dots
Jens H. van Dalfsen, PhD, a postdoctoral researcher in biological psychiatry, is the principal investigator of another UMCG group looking into the neurobiological mechanisms of major depressive disorder and treatment-resistant depression. His team’s strategy entails an elaborate coordination between the preclinical and clinical research settings.
For example, Sarah Massetti, a PhD candidate in biological psychiatry, is using blood samples collected in clinical trials to investigate the molecular mechanisms underpinning the neuroplasticity and immune-modulating effects produced by psychedelic compounds.
Another line of research spearheaded by Rutger Boesjes, a PhD candidate in biological psychiatry, is exploring the interactions between drugs like ketamine and the circadian system and how they might relate to antidepressant responses in animal models. It could be that the timing of administration of these drugs is relevant, he explained.
The Patient Factor
How psychedelics work and in whom is a big question for the UMCG team and across the research landscape.
“When researchers and the general public talk about psychedelics, they frequently refer to how they promote synaptic plasticity and new connections in the brain,” said van Dalfsen. “But traditional compounds also do that. So the ultimate question that we’ve been exploring is whether findings reflect an actual pharmacological effect or if expectancy also plays a role. In other words: How can we explain why psychedelics might or might not be effective in treatment-resistant patients?” he explained.
This is where the connection to the clinical experience becomes paramount and Joost Breeksema, PhD, comes in.
Breeksema divides his time between UMCG research and his role as executive director and co-founder of the Open Foundation, a nonprofit dedicated to advancing scientific psychedelic research. The work he’s doing outside the university is helping to frame the investigations of the wider group.
So far he has conducted two qualitative studies.
One was an off-label study in which patients with treatment-resistant depression were administered esketamine.
The other was a randomized clinical trial in which participants were blinded to a single 10- or 25-mg dose of psilocybin versus a 1-mg psilocybin microdose placebo that is too small to invoke any effects.
A key insight was the degree to which participants were unprepared for the intensity of their experiences, especially with regards to ketamine. Breeksema said the sessions might not have been so intense or negative for some participants had they been informed beforehand to expect the drugs could provoke “quite overwhelming experiences” and had they been accompanied by an experienced guide providing reassurance and support.
The format for the psilocybin trial met part of this criteria. Participants received a micro (placebo), medium, or high dose in a single session accompanied by two trained therapists. They then engaged in two sessions afterward to process their experiences. A single psilocybin experience appeared to be not enough or too much depending on the dose they were assigned and if they had prior experience with the compound.
Trial participants also felt they needed more help making sense of the experience. “This is a common and important theme,” said Breeksema. “Think about it. If you’ve been depressed for 10, 15 years and … you uncover something and break through something that’s been stuck, you need to process it.”
Jeanine Kamphuis, PhD, a psychiatrist and senior researcher at UMCG and one of the trial study co-authors, explained that they want to find a way to identify who will be too overwhelmed by these experiences if the dose should be adjusted or if some time needs to pass between dosing sessions. They also want to spend more time preparing patients for these sessions.
She emphasized that the studies have provided a reality check. “These are not wonder pills or wonder experiences. And in these types of patients, they’re not intended for a personal growth experience,” she said. “You have a patient who is sitting in front of you who seeks therapy and relief from very severe mood complaints, and the suffering is high,” she said, adding that expectancy bias further complicates patient participation and, likely, outcomes.
The Challenges
For all the potential and opportunity that psychedelics may hold for treatment, UMCG’s work has underscored some challenges.
The field of psychedelic research is characterized by methodological issues, explained van Dalfsen, such as blinding, expectancy, and overestimation of treatment effects. When looking at efficacy, “Is it the compound or the expectancy and promise? This is why it’s important to study how the drugs differ from each other in their biological effects and why they are or are not effective,” he said.
The team has also experienced issues with trial recruitment.
Martijn Godschalk, MD, a PhD candidate in psychiatry, has been addressing this problem while working on RESET-TRD, a phase 3, randomized controlled trial comparing an oral esketamine drink with electroconvulsive therapy in patients with treatment-resistant depression.
He’s been coordinating with local university hospitals, general hospitals, and municipal healthcare clinics to meet inclusion criteria and ensure the trial has enough power to demonstrate effectiveness. In turn, these sites are able to participate in a trial they wouldn’t normally be involved in due to lack of resources.
But Godschalk said he was concerned that many patients have gotten wind of the hype surrounding psychedelic treatments within psychiatry — a factor that has contributed to recruitment challenges. “There are a lot of patients who are interested in the non-registered drug and don’t necessarily have an interest in the other [control] arm,” he said.
Despite the challenges, the classic psychedelics such as MDMA and psilocybin “seem to catalyze a psychological process that may be harder to get with regular psychotherapies,” said Schoevers.
He remains cautious, noting there are still unanswered questions, such as who are the best candidates for these drugs and whether they might cause harm in certain patients while benefiting others. “I do think that this is the first time in 20 or 30 years that there is a group of potential treatments that would really make a difference.”
Schoevers received grants and other funding from The Netherlands Organisation for Health Research & Development, Horizon 2020, Horizon 2023, the National Institute of Mental Health (USA), UMCG, Stichting tot Steun VCVGZ, Nationaal programma Groningen, Healthcare Innovation Funds, Janssen Pharmaceuticals, Novartis, Compass Pathways, Clexio Biosciences, and GH research.
A version of this article appeared on Medscape.com.
AI in Medicine: Are Large Language Models Ready for the Exam Room?
In seconds, Ravi Parikh, MD, an oncologist at the Emory University School of Medicine in Atlanta, had a summary of his patient’s entire medical history. Normally, Parikh skimmed the cumbersome files before seeing a patient. However, the artificial intelligence (AI) tool his institution was testing could list the highlights he needed in a fraction of the time.
“On the whole, I like it ... it saves me time,” Parikh said of the tool. “But I’d be lying if I told you it was perfect all the time. It’s interpreting the [patient] history in some ways that may be inaccurate,” he said.
Within the first week of testing the tool, Parikh started to notice that the large language model (LLM) made a particular mistake in his patients with prostate cancer. If their prostate-specific antigen test results came back slightly elevated — which is part of normal variation — the LLM recorded it as disease progression. Because Parikh reviews all his notes — with or without using an AI tool — after a visit, he easily caught the mistake before it was added to the chart. “The problem, I think, is if these mistakes go under the hood,” he said.
In the data science world, these mistakes are called hallucinations. And a growing body of research suggests they’re happening more frequently than is safe for healthcare. The industry promised LLMs would alleviate administrative burden and reduce physician burnout. But so far, studies show these AI-tool mistakes often create more work for doctors, not less. To truly help physicians and be safe for patients, some experts say healthcare needs to build its own LLMs from the ground up. And all agree that the field desperately needs a way to vet these algorithms more thoroughly.
Prone to Error
Right now, “I think the industry is focused on taking existing LLMs and forcing them into usage for healthcare,” said Nigam H. Shah, MBBS, PhD, chief data scientist for Stanford Health. However, the value of deploying general LLMs in the healthcare space is questionable. “People are starting to wonder if we’re using these tools wrong,” he told this news organization.
In 2023, Shah and his colleagues evaluated seven LLMs on their ability to answer electronic health record–based questions. For realistic tasks, the error rate in the best cases was about 35%, he said. “To me, that rate seems a bit high ... to adopt for routine use.”
A study earlier this year by the UC San Diego School of Medicine showed that using LLMs to respond to patient messages increased the time doctors spent on messages. And this summer, a study by the clinical AI firm Mendel found that when GPT-4o or Llama-3 were used to summarize patient medical records, almost every summary contained at least one type of hallucination.
“We’ve seen cases where a patient does have drug allergies, but the system says ‘no known drug allergies’ ” in the medical history summary, said Wael Salloum, PhD, cofounder and chief science officer at Mendel. “That’s a serious hallucination.” And if physicians have to constantly verify what the system is telling them, that “defeats the purpose [of summarization],” he said.
A Higher Quality Diet
Part of the trouble with LLMs is that there’s just not enough high-quality information to feed them. The algorithms are insatiable, requiring vast swaths of data for training. GPT-3.5, for instance, was trained on 570 GB of data from the internet, more than 300 billion words. And to train GPT-4o, OpenAI reportedly transcribed more than 1 million hours of YouTube content.
However, the strategies that built these general LLMs don’t always translate well to healthcare. The internet is full of low-quality or misleading health information from wellness sites and supplement advertisements. And even data that are trustworthy, like the millions of clinical studies and the US Food and Drug Administration (FDA) statements, can be outdated, Salloum said. And “an LLM in training can’t distinguish good from bad,” he added.
The good news is that clinicians don’t rely on controversial information in the real world. Medical knowledge is standardized. “Healthcare is a domain rich with explicit knowledge,” Salloum said. So there’s potential to build a more reliable LLM that is guided by robust medical standards and guidelines.
It’s possible that healthcare could use small language models, which are LLM’s pocket-sized cousins, and perform tasks needing only bite-sized datasets requiring fewer resources and easier fine-tuning, according to Microsoft’s website. Shah said training these smaller models on real medical data might be an option, like an LLM meant to respond to patient messages that could be trained with real messages sent by physicians.
Several groups are already working on databases of standardized human medical knowledge or real physician responses. “Perhaps that will work better than using LLMs trained on the general internet. Those studies need to be done,” Shah said.
Jon Tamir, assistant professor of electrical and computer engineering and co-lead of the AI Health Lab at The University of Texas at Austin, said, “The community has recognized that we are entering a new era of AI where the dataset itself is the most important aspect. We need training sets that are highly curated and highly specialized.
“If the dataset is highly specialized, it will definitely help reduce hallucinations,” he said.
Cutting Overconfidence
A major problem with LLM mistakes is that they are often hard to detect. Hallucinations can be highly convincing even if they’re highly inaccurate, according to Tamir.
When Shah, for instance, was recently testing an LLM on de-identified patient data, he asked the LLM which blood test the patient last had. The model responded with “complete blood count [CBC].” But when he asked for the results, the model gave him white blood count and other values. “Turns out that record did not have a CBC done at all! The result was entirely made up,” he said.
Making healthcare LLMs safer and more reliable will mean training AI to acknowledge potential mistakes and uncertainty. Existing LLMs are trained to project confidence and produce a lot of answers, even when there isn’t one, Salloum said. They rarely respond with “I don’t know” even when their prediction has low confidence, he added.
Healthcare stands to benefit from a system that highlights uncertainty and potential errors. For instance, if a patient’s history shows they have smoked, stopped smoking, vaped, and started smoking again. The LLM might call them a smoker but flag the comment as uncertain because the chronology is complicated, Salloum said.
Tamir added that this strategy could improve LLM and doctor collaboration by honing in on where human expertise is needed most.
Too Little Evaluation
For any improvement strategy to work, LLMs — and all AI-assisted healthcare tools — first need a better evaluation framework. So far, LLMs have “been used in really exciting ways but not really well-vetted ways,” Tamir said.
While some AI-assisted tools, particularly in medical imaging, have undergone rigorous FDA evaluations and earned approval, most haven’t. And because the FDA only regulates algorithms that are considered medical devices, Parikh said that most LLMs used for administrative tasks and efficiency don’t fall under the regulatory agency’s purview.
But these algorithms still have access to patient information and can directly influence patient and doctor decisions. Third-party regulatory agencies are expected to emerge, but it’s still unclear who those will be. Before developers can build a safer and more efficient LLM for healthcare, they’ll need better guidelines and guardrails. “Unless we figure out evaluation, how would we know whether the healthcare-appropriate large language models are better or worse?” Shah asked.
A version of this article appeared on Medscape.com.
In seconds, Ravi Parikh, MD, an oncologist at the Emory University School of Medicine in Atlanta, had a summary of his patient’s entire medical history. Normally, Parikh skimmed the cumbersome files before seeing a patient. However, the artificial intelligence (AI) tool his institution was testing could list the highlights he needed in a fraction of the time.
“On the whole, I like it ... it saves me time,” Parikh said of the tool. “But I’d be lying if I told you it was perfect all the time. It’s interpreting the [patient] history in some ways that may be inaccurate,” he said.
Within the first week of testing the tool, Parikh started to notice that the large language model (LLM) made a particular mistake in his patients with prostate cancer. If their prostate-specific antigen test results came back slightly elevated — which is part of normal variation — the LLM recorded it as disease progression. Because Parikh reviews all his notes — with or without using an AI tool — after a visit, he easily caught the mistake before it was added to the chart. “The problem, I think, is if these mistakes go under the hood,” he said.
In the data science world, these mistakes are called hallucinations. And a growing body of research suggests they’re happening more frequently than is safe for healthcare. The industry promised LLMs would alleviate administrative burden and reduce physician burnout. But so far, studies show these AI-tool mistakes often create more work for doctors, not less. To truly help physicians and be safe for patients, some experts say healthcare needs to build its own LLMs from the ground up. And all agree that the field desperately needs a way to vet these algorithms more thoroughly.
Prone to Error
Right now, “I think the industry is focused on taking existing LLMs and forcing them into usage for healthcare,” said Nigam H. Shah, MBBS, PhD, chief data scientist for Stanford Health. However, the value of deploying general LLMs in the healthcare space is questionable. “People are starting to wonder if we’re using these tools wrong,” he told this news organization.
In 2023, Shah and his colleagues evaluated seven LLMs on their ability to answer electronic health record–based questions. For realistic tasks, the error rate in the best cases was about 35%, he said. “To me, that rate seems a bit high ... to adopt for routine use.”
A study earlier this year by the UC San Diego School of Medicine showed that using LLMs to respond to patient messages increased the time doctors spent on messages. And this summer, a study by the clinical AI firm Mendel found that when GPT-4o or Llama-3 were used to summarize patient medical records, almost every summary contained at least one type of hallucination.
“We’ve seen cases where a patient does have drug allergies, but the system says ‘no known drug allergies’ ” in the medical history summary, said Wael Salloum, PhD, cofounder and chief science officer at Mendel. “That’s a serious hallucination.” And if physicians have to constantly verify what the system is telling them, that “defeats the purpose [of summarization],” he said.
A Higher Quality Diet
Part of the trouble with LLMs is that there’s just not enough high-quality information to feed them. The algorithms are insatiable, requiring vast swaths of data for training. GPT-3.5, for instance, was trained on 570 GB of data from the internet, more than 300 billion words. And to train GPT-4o, OpenAI reportedly transcribed more than 1 million hours of YouTube content.
However, the strategies that built these general LLMs don’t always translate well to healthcare. The internet is full of low-quality or misleading health information from wellness sites and supplement advertisements. And even data that are trustworthy, like the millions of clinical studies and the US Food and Drug Administration (FDA) statements, can be outdated, Salloum said. And “an LLM in training can’t distinguish good from bad,” he added.
The good news is that clinicians don’t rely on controversial information in the real world. Medical knowledge is standardized. “Healthcare is a domain rich with explicit knowledge,” Salloum said. So there’s potential to build a more reliable LLM that is guided by robust medical standards and guidelines.
It’s possible that healthcare could use small language models, which are LLM’s pocket-sized cousins, and perform tasks needing only bite-sized datasets requiring fewer resources and easier fine-tuning, according to Microsoft’s website. Shah said training these smaller models on real medical data might be an option, like an LLM meant to respond to patient messages that could be trained with real messages sent by physicians.
Several groups are already working on databases of standardized human medical knowledge or real physician responses. “Perhaps that will work better than using LLMs trained on the general internet. Those studies need to be done,” Shah said.
Jon Tamir, assistant professor of electrical and computer engineering and co-lead of the AI Health Lab at The University of Texas at Austin, said, “The community has recognized that we are entering a new era of AI where the dataset itself is the most important aspect. We need training sets that are highly curated and highly specialized.
“If the dataset is highly specialized, it will definitely help reduce hallucinations,” he said.
Cutting Overconfidence
A major problem with LLM mistakes is that they are often hard to detect. Hallucinations can be highly convincing even if they’re highly inaccurate, according to Tamir.
When Shah, for instance, was recently testing an LLM on de-identified patient data, he asked the LLM which blood test the patient last had. The model responded with “complete blood count [CBC].” But when he asked for the results, the model gave him white blood count and other values. “Turns out that record did not have a CBC done at all! The result was entirely made up,” he said.
Making healthcare LLMs safer and more reliable will mean training AI to acknowledge potential mistakes and uncertainty. Existing LLMs are trained to project confidence and produce a lot of answers, even when there isn’t one, Salloum said. They rarely respond with “I don’t know” even when their prediction has low confidence, he added.
Healthcare stands to benefit from a system that highlights uncertainty and potential errors. For instance, if a patient’s history shows they have smoked, stopped smoking, vaped, and started smoking again. The LLM might call them a smoker but flag the comment as uncertain because the chronology is complicated, Salloum said.
Tamir added that this strategy could improve LLM and doctor collaboration by honing in on where human expertise is needed most.
Too Little Evaluation
For any improvement strategy to work, LLMs — and all AI-assisted healthcare tools — first need a better evaluation framework. So far, LLMs have “been used in really exciting ways but not really well-vetted ways,” Tamir said.
While some AI-assisted tools, particularly in medical imaging, have undergone rigorous FDA evaluations and earned approval, most haven’t. And because the FDA only regulates algorithms that are considered medical devices, Parikh said that most LLMs used for administrative tasks and efficiency don’t fall under the regulatory agency’s purview.
But these algorithms still have access to patient information and can directly influence patient and doctor decisions. Third-party regulatory agencies are expected to emerge, but it’s still unclear who those will be. Before developers can build a safer and more efficient LLM for healthcare, they’ll need better guidelines and guardrails. “Unless we figure out evaluation, how would we know whether the healthcare-appropriate large language models are better or worse?” Shah asked.
A version of this article appeared on Medscape.com.
In seconds, Ravi Parikh, MD, an oncologist at the Emory University School of Medicine in Atlanta, had a summary of his patient’s entire medical history. Normally, Parikh skimmed the cumbersome files before seeing a patient. However, the artificial intelligence (AI) tool his institution was testing could list the highlights he needed in a fraction of the time.
“On the whole, I like it ... it saves me time,” Parikh said of the tool. “But I’d be lying if I told you it was perfect all the time. It’s interpreting the [patient] history in some ways that may be inaccurate,” he said.
Within the first week of testing the tool, Parikh started to notice that the large language model (LLM) made a particular mistake in his patients with prostate cancer. If their prostate-specific antigen test results came back slightly elevated — which is part of normal variation — the LLM recorded it as disease progression. Because Parikh reviews all his notes — with or without using an AI tool — after a visit, he easily caught the mistake before it was added to the chart. “The problem, I think, is if these mistakes go under the hood,” he said.
In the data science world, these mistakes are called hallucinations. And a growing body of research suggests they’re happening more frequently than is safe for healthcare. The industry promised LLMs would alleviate administrative burden and reduce physician burnout. But so far, studies show these AI-tool mistakes often create more work for doctors, not less. To truly help physicians and be safe for patients, some experts say healthcare needs to build its own LLMs from the ground up. And all agree that the field desperately needs a way to vet these algorithms more thoroughly.
Prone to Error
Right now, “I think the industry is focused on taking existing LLMs and forcing them into usage for healthcare,” said Nigam H. Shah, MBBS, PhD, chief data scientist for Stanford Health. However, the value of deploying general LLMs in the healthcare space is questionable. “People are starting to wonder if we’re using these tools wrong,” he told this news organization.
In 2023, Shah and his colleagues evaluated seven LLMs on their ability to answer electronic health record–based questions. For realistic tasks, the error rate in the best cases was about 35%, he said. “To me, that rate seems a bit high ... to adopt for routine use.”
A study earlier this year by the UC San Diego School of Medicine showed that using LLMs to respond to patient messages increased the time doctors spent on messages. And this summer, a study by the clinical AI firm Mendel found that when GPT-4o or Llama-3 were used to summarize patient medical records, almost every summary contained at least one type of hallucination.
“We’ve seen cases where a patient does have drug allergies, but the system says ‘no known drug allergies’ ” in the medical history summary, said Wael Salloum, PhD, cofounder and chief science officer at Mendel. “That’s a serious hallucination.” And if physicians have to constantly verify what the system is telling them, that “defeats the purpose [of summarization],” he said.
A Higher Quality Diet
Part of the trouble with LLMs is that there’s just not enough high-quality information to feed them. The algorithms are insatiable, requiring vast swaths of data for training. GPT-3.5, for instance, was trained on 570 GB of data from the internet, more than 300 billion words. And to train GPT-4o, OpenAI reportedly transcribed more than 1 million hours of YouTube content.
However, the strategies that built these general LLMs don’t always translate well to healthcare. The internet is full of low-quality or misleading health information from wellness sites and supplement advertisements. And even data that are trustworthy, like the millions of clinical studies and the US Food and Drug Administration (FDA) statements, can be outdated, Salloum said. And “an LLM in training can’t distinguish good from bad,” he added.
The good news is that clinicians don’t rely on controversial information in the real world. Medical knowledge is standardized. “Healthcare is a domain rich with explicit knowledge,” Salloum said. So there’s potential to build a more reliable LLM that is guided by robust medical standards and guidelines.
It’s possible that healthcare could use small language models, which are LLM’s pocket-sized cousins, and perform tasks needing only bite-sized datasets requiring fewer resources and easier fine-tuning, according to Microsoft’s website. Shah said training these smaller models on real medical data might be an option, like an LLM meant to respond to patient messages that could be trained with real messages sent by physicians.
Several groups are already working on databases of standardized human medical knowledge or real physician responses. “Perhaps that will work better than using LLMs trained on the general internet. Those studies need to be done,” Shah said.
Jon Tamir, assistant professor of electrical and computer engineering and co-lead of the AI Health Lab at The University of Texas at Austin, said, “The community has recognized that we are entering a new era of AI where the dataset itself is the most important aspect. We need training sets that are highly curated and highly specialized.
“If the dataset is highly specialized, it will definitely help reduce hallucinations,” he said.
Cutting Overconfidence
A major problem with LLM mistakes is that they are often hard to detect. Hallucinations can be highly convincing even if they’re highly inaccurate, according to Tamir.
When Shah, for instance, was recently testing an LLM on de-identified patient data, he asked the LLM which blood test the patient last had. The model responded with “complete blood count [CBC].” But when he asked for the results, the model gave him white blood count and other values. “Turns out that record did not have a CBC done at all! The result was entirely made up,” he said.
Making healthcare LLMs safer and more reliable will mean training AI to acknowledge potential mistakes and uncertainty. Existing LLMs are trained to project confidence and produce a lot of answers, even when there isn’t one, Salloum said. They rarely respond with “I don’t know” even when their prediction has low confidence, he added.
Healthcare stands to benefit from a system that highlights uncertainty and potential errors. For instance, if a patient’s history shows they have smoked, stopped smoking, vaped, and started smoking again. The LLM might call them a smoker but flag the comment as uncertain because the chronology is complicated, Salloum said.
Tamir added that this strategy could improve LLM and doctor collaboration by honing in on where human expertise is needed most.
Too Little Evaluation
For any improvement strategy to work, LLMs — and all AI-assisted healthcare tools — first need a better evaluation framework. So far, LLMs have “been used in really exciting ways but not really well-vetted ways,” Tamir said.
While some AI-assisted tools, particularly in medical imaging, have undergone rigorous FDA evaluations and earned approval, most haven’t. And because the FDA only regulates algorithms that are considered medical devices, Parikh said that most LLMs used for administrative tasks and efficiency don’t fall under the regulatory agency’s purview.
But these algorithms still have access to patient information and can directly influence patient and doctor decisions. Third-party regulatory agencies are expected to emerge, but it’s still unclear who those will be. Before developers can build a safer and more efficient LLM for healthcare, they’ll need better guidelines and guardrails. “Unless we figure out evaluation, how would we know whether the healthcare-appropriate large language models are better or worse?” Shah asked.
A version of this article appeared on Medscape.com.
Family Medicine–Led Obstetric Units Achieve Lower C-Section Rates, Better Safety Culture
Labor and delivery centers run by family medicine (FM) healthcare providers have a lower cesarean delivery rate and better safety culture than centers led by obstetricians (OBs), based on observational data from Iowa hospitals.
These findings show how FM providers backed up by general surgeons can deliver a high standard of obstetric care, suggesting that this team-based model could address growing maternity care deserts across the United States, lead author Emily White VanGompel, MD, of the University of Illinois College of Medicine in Chicago, and colleagues reported.
“Despite decades of research documenting the high quality of care provided by FM physicians, controversy continues regarding whether family physicians trained in existing FM residency programs should provide intrapartum obstetric care,” the investigators wrote in Annals of Family Medicine.
This controversy, though long-standing, has gained more attention in the past decade with worsening severe maternal morbidity and maternal health disparities in rural areas, along with state-based perinatal quality initiatives to improve care and reduce severe maternal morbidity. These efforts have largely involved obstetric, nursing, and midwifery organizations, with minimal input from FM professionals.
The role of FM in these initiatives therefore remains unexplored.
This is a clear blind spot, according to White VanGompel and colleagues, who noted that 40% of counties in the United States do not have an OB or a midwife, while only 6.5% of counties lack an FM physician. In other words, FM providers may be the most rational — and widely available — specialty to close gaps in obstetric care.
Study Reveals Fewer C-Sections, Better Safety Culture Among FM-Led Centers
To explore the viability of an FM-led model, the investigators used a cross-sectional survey to assess the relationship between staffing models and perinatal outcomes. A total of 849 clinicians, including physicians, nurses, and midwives from 39 hospitals, were surveyed as part of a statewide quality improvement initiative designed to reduce cesarean delivery rates. The hospitals were categorized on the basis of the type of physician providing intrapartum care: Some hospitals were staffed exclusively by FM physicians (13), some by OBs only (11), and others by both types of providers (15).
The primary outcome measured was the low-risk cesarean delivery rate, specifically the nulliparous, term, singleton, vertex cesarean delivery rate.
The study found that FM-only hospitals, all of which were located in rural areas with fewer than 1000 annual births, had significantly lower cesarean delivery rates than hospitals with mixed or OB-only staffing. After adjusting for factors such as hospital birth volume, geographic location, patient body mass index, maternal age, and insurance status, FM-only hospitals had an adjusted 34.3% lower rate of cesarean sections than hospitals with both FM and OB physicians (adjusted incidence rate ratio, 0.66; 95% CI, 0.52-0.98).
In addition to lower cesarean delivery rates, the study revealed that hospitals staffed exclusively by FM physicians reported a stronger safety culture, as measured by nurse perceptions of unit norms supporting vaginal birth. Nurses at FM-only hospitals were more likely to endorse safety practices that favored vaginal delivery, a finding that was statistically significant. The study also found that nurses at FM-only hospitals rated overall unit safety culture higher than those at hospitals staffed solely by OBs or a combination of FM physicians and OBs.
“I’m not surprised [by these findings],” said Joedrecka S. Brown Speights, MD, professor and chair of the Department of Family Medicine and Rural Health at Florida State University College of Medicine, Tallahassee.
She noted that the data echo previous reports demonstrating the broader benefits of FM involvement.
“When people get primary care, life is better,” Brown Speights said, citing improved outcomes, greater health equity, and lower overall healthcare costs associated with high-quality primary care.
“That’s what we need for women and for pregnant persons, especially in rural areas,” she said.
The Model Itself Could Be the Biggest Finding
According to White VanGompel, the biggest finding from the study is the existence of the team-based model itself — where FM providers lead obstetric care with support from general surgeons.
“Quite honestly, many people around the country, including family physicians like myself, did not know [this model] existed and was thriving in these rural areas that are on the verge of becoming maternity care deserts,” White VanGompel said in an interview. “That makes a huge difference clinically because those are patients that otherwise wouldn’t have access to comprehensive pregnancy care.”
This FM-led model has the added advantage of improving continuity of care, she added, noting that issues like maternal mental health — a major contributor to postpartum morbidity and mortality — are a primary care issue.
“If we are not involved in that patient’s pregnancy care, and we don’t know that they’ve had this postpartum course or they’ve had antepartum depression, it’s very hard for us to then jump in and accurately treat that person,” White VanGompel said. “If we’re involved in the entire course of care, we can make that contribution.”
Emilio A. Russo, MD, Marie Lahasky Professor of Family Medicine and chair of the Department of Family Medicine at Louisiana State University (LSU) Health Sciences Center New Orleans, and program director of the LSU Rural Family Medicine Program, Bogalusa, Louisiana, agreed that FM providers’ more continuous care, along with experience treating both mothers and babies, make them invaluable in the maternity care setting.
“We are missing the opportunity to incorporate family physicians and nurse midwives into the continuum of care for women, especially in these remote areas,” Russo said in an interview. “Family physicians and nurse midwives are the only two [groups] in the health system trained and licensed to care for both mother and baby, and I have to believe that there’s something profoundly important about that.”
Barriers May Block FM Providers From Obstetric Practice
In a recent Birth editorial, Simone Hampton, MD, of Carle Health Family Medicine, Urbana, Illinois, explored a key question: Why aren’t we using FM to help confront the maternal mortality crisis in the United States?
Hampton described how obstetric care is often siloed between specialties and barriers, including insufficient training, organizational constraints, and malpractice coverage, deter FM physicians from practicing obstetrics.
In an additional written comment, Hampton suggested that family doctors also face misconceptions about their ability to provide obstetric care, even with rigorous training and a comprehensive skill set.
“We are interested in caring for families,” Hampton said, emphasizing how FM providers are uniquely trained to care for the maternal dyad in a way that OBs are not and often view birth as a more natural process that typically does not require intervention.
Unfortunately, hospital administrators often maintain a different view, Brown Speights said, describing how some centers limit obstetric care privileges exclusively to OBs or require case volume minimums that can be tough to reach in a rural setting.
“If you have low-volume places, you can have a challenge meeting the numbers to keep up the requirements to get credentialed to practice obstetrics at the hospital,” she said, which only exacerbates gaps in maternity care access.
“This type of skill set in a rural place often, by default, represents a lower volume,” Russo said. “So how do the interests of competency and access intersect in this space?”
Generating more data to support the quality of FM-led obstetric models could be the clearest path forward, according to White VanGompel. She suggested that team-based approaches like the one described in the present study deserve further investigation in other hospital systems.
Until then, this gap in maternity care remains an ongoing, and often personal, concern.
“The more I do this quality work, the more I’m in these rooms where I’m the only family physician and I’m surrounded by all of these amazing labor and delivery nurses and obstetricians and maternal-fetal medicine doctors and midwives and doulas,” White VanGompel said. “I’m just constantly asking myself, Why am I the only family doctor in the room?”
This study was supported by the Agency for Healthcare Research and Quality and the North Shore Auxiliary. The Iowa Maternal Quality Care Collaborative is supported by a State Maternal Health Innovation award from the Health Resources and Services Administration. The investigators, Hampton and Brown Speights, disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Labor and delivery centers run by family medicine (FM) healthcare providers have a lower cesarean delivery rate and better safety culture than centers led by obstetricians (OBs), based on observational data from Iowa hospitals.
These findings show how FM providers backed up by general surgeons can deliver a high standard of obstetric care, suggesting that this team-based model could address growing maternity care deserts across the United States, lead author Emily White VanGompel, MD, of the University of Illinois College of Medicine in Chicago, and colleagues reported.
“Despite decades of research documenting the high quality of care provided by FM physicians, controversy continues regarding whether family physicians trained in existing FM residency programs should provide intrapartum obstetric care,” the investigators wrote in Annals of Family Medicine.
This controversy, though long-standing, has gained more attention in the past decade with worsening severe maternal morbidity and maternal health disparities in rural areas, along with state-based perinatal quality initiatives to improve care and reduce severe maternal morbidity. These efforts have largely involved obstetric, nursing, and midwifery organizations, with minimal input from FM professionals.
The role of FM in these initiatives therefore remains unexplored.
This is a clear blind spot, according to White VanGompel and colleagues, who noted that 40% of counties in the United States do not have an OB or a midwife, while only 6.5% of counties lack an FM physician. In other words, FM providers may be the most rational — and widely available — specialty to close gaps in obstetric care.
Study Reveals Fewer C-Sections, Better Safety Culture Among FM-Led Centers
To explore the viability of an FM-led model, the investigators used a cross-sectional survey to assess the relationship between staffing models and perinatal outcomes. A total of 849 clinicians, including physicians, nurses, and midwives from 39 hospitals, were surveyed as part of a statewide quality improvement initiative designed to reduce cesarean delivery rates. The hospitals were categorized on the basis of the type of physician providing intrapartum care: Some hospitals were staffed exclusively by FM physicians (13), some by OBs only (11), and others by both types of providers (15).
The primary outcome measured was the low-risk cesarean delivery rate, specifically the nulliparous, term, singleton, vertex cesarean delivery rate.
The study found that FM-only hospitals, all of which were located in rural areas with fewer than 1000 annual births, had significantly lower cesarean delivery rates than hospitals with mixed or OB-only staffing. After adjusting for factors such as hospital birth volume, geographic location, patient body mass index, maternal age, and insurance status, FM-only hospitals had an adjusted 34.3% lower rate of cesarean sections than hospitals with both FM and OB physicians (adjusted incidence rate ratio, 0.66; 95% CI, 0.52-0.98).
In addition to lower cesarean delivery rates, the study revealed that hospitals staffed exclusively by FM physicians reported a stronger safety culture, as measured by nurse perceptions of unit norms supporting vaginal birth. Nurses at FM-only hospitals were more likely to endorse safety practices that favored vaginal delivery, a finding that was statistically significant. The study also found that nurses at FM-only hospitals rated overall unit safety culture higher than those at hospitals staffed solely by OBs or a combination of FM physicians and OBs.
“I’m not surprised [by these findings],” said Joedrecka S. Brown Speights, MD, professor and chair of the Department of Family Medicine and Rural Health at Florida State University College of Medicine, Tallahassee.
She noted that the data echo previous reports demonstrating the broader benefits of FM involvement.
“When people get primary care, life is better,” Brown Speights said, citing improved outcomes, greater health equity, and lower overall healthcare costs associated with high-quality primary care.
“That’s what we need for women and for pregnant persons, especially in rural areas,” she said.
The Model Itself Could Be the Biggest Finding
According to White VanGompel, the biggest finding from the study is the existence of the team-based model itself — where FM providers lead obstetric care with support from general surgeons.
“Quite honestly, many people around the country, including family physicians like myself, did not know [this model] existed and was thriving in these rural areas that are on the verge of becoming maternity care deserts,” White VanGompel said in an interview. “That makes a huge difference clinically because those are patients that otherwise wouldn’t have access to comprehensive pregnancy care.”
This FM-led model has the added advantage of improving continuity of care, she added, noting that issues like maternal mental health — a major contributor to postpartum morbidity and mortality — are a primary care issue.
“If we are not involved in that patient’s pregnancy care, and we don’t know that they’ve had this postpartum course or they’ve had antepartum depression, it’s very hard for us to then jump in and accurately treat that person,” White VanGompel said. “If we’re involved in the entire course of care, we can make that contribution.”
Emilio A. Russo, MD, Marie Lahasky Professor of Family Medicine and chair of the Department of Family Medicine at Louisiana State University (LSU) Health Sciences Center New Orleans, and program director of the LSU Rural Family Medicine Program, Bogalusa, Louisiana, agreed that FM providers’ more continuous care, along with experience treating both mothers and babies, make them invaluable in the maternity care setting.
“We are missing the opportunity to incorporate family physicians and nurse midwives into the continuum of care for women, especially in these remote areas,” Russo said in an interview. “Family physicians and nurse midwives are the only two [groups] in the health system trained and licensed to care for both mother and baby, and I have to believe that there’s something profoundly important about that.”
Barriers May Block FM Providers From Obstetric Practice
In a recent Birth editorial, Simone Hampton, MD, of Carle Health Family Medicine, Urbana, Illinois, explored a key question: Why aren’t we using FM to help confront the maternal mortality crisis in the United States?
Hampton described how obstetric care is often siloed between specialties and barriers, including insufficient training, organizational constraints, and malpractice coverage, deter FM physicians from practicing obstetrics.
In an additional written comment, Hampton suggested that family doctors also face misconceptions about their ability to provide obstetric care, even with rigorous training and a comprehensive skill set.
“We are interested in caring for families,” Hampton said, emphasizing how FM providers are uniquely trained to care for the maternal dyad in a way that OBs are not and often view birth as a more natural process that typically does not require intervention.
Unfortunately, hospital administrators often maintain a different view, Brown Speights said, describing how some centers limit obstetric care privileges exclusively to OBs or require case volume minimums that can be tough to reach in a rural setting.
“If you have low-volume places, you can have a challenge meeting the numbers to keep up the requirements to get credentialed to practice obstetrics at the hospital,” she said, which only exacerbates gaps in maternity care access.
“This type of skill set in a rural place often, by default, represents a lower volume,” Russo said. “So how do the interests of competency and access intersect in this space?”
Generating more data to support the quality of FM-led obstetric models could be the clearest path forward, according to White VanGompel. She suggested that team-based approaches like the one described in the present study deserve further investigation in other hospital systems.
Until then, this gap in maternity care remains an ongoing, and often personal, concern.
“The more I do this quality work, the more I’m in these rooms where I’m the only family physician and I’m surrounded by all of these amazing labor and delivery nurses and obstetricians and maternal-fetal medicine doctors and midwives and doulas,” White VanGompel said. “I’m just constantly asking myself, Why am I the only family doctor in the room?”
This study was supported by the Agency for Healthcare Research and Quality and the North Shore Auxiliary. The Iowa Maternal Quality Care Collaborative is supported by a State Maternal Health Innovation award from the Health Resources and Services Administration. The investigators, Hampton and Brown Speights, disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Labor and delivery centers run by family medicine (FM) healthcare providers have a lower cesarean delivery rate and better safety culture than centers led by obstetricians (OBs), based on observational data from Iowa hospitals.
These findings show how FM providers backed up by general surgeons can deliver a high standard of obstetric care, suggesting that this team-based model could address growing maternity care deserts across the United States, lead author Emily White VanGompel, MD, of the University of Illinois College of Medicine in Chicago, and colleagues reported.
“Despite decades of research documenting the high quality of care provided by FM physicians, controversy continues regarding whether family physicians trained in existing FM residency programs should provide intrapartum obstetric care,” the investigators wrote in Annals of Family Medicine.
This controversy, though long-standing, has gained more attention in the past decade with worsening severe maternal morbidity and maternal health disparities in rural areas, along with state-based perinatal quality initiatives to improve care and reduce severe maternal morbidity. These efforts have largely involved obstetric, nursing, and midwifery organizations, with minimal input from FM professionals.
The role of FM in these initiatives therefore remains unexplored.
This is a clear blind spot, according to White VanGompel and colleagues, who noted that 40% of counties in the United States do not have an OB or a midwife, while only 6.5% of counties lack an FM physician. In other words, FM providers may be the most rational — and widely available — specialty to close gaps in obstetric care.
Study Reveals Fewer C-Sections, Better Safety Culture Among FM-Led Centers
To explore the viability of an FM-led model, the investigators used a cross-sectional survey to assess the relationship between staffing models and perinatal outcomes. A total of 849 clinicians, including physicians, nurses, and midwives from 39 hospitals, were surveyed as part of a statewide quality improvement initiative designed to reduce cesarean delivery rates. The hospitals were categorized on the basis of the type of physician providing intrapartum care: Some hospitals were staffed exclusively by FM physicians (13), some by OBs only (11), and others by both types of providers (15).
The primary outcome measured was the low-risk cesarean delivery rate, specifically the nulliparous, term, singleton, vertex cesarean delivery rate.
The study found that FM-only hospitals, all of which were located in rural areas with fewer than 1000 annual births, had significantly lower cesarean delivery rates than hospitals with mixed or OB-only staffing. After adjusting for factors such as hospital birth volume, geographic location, patient body mass index, maternal age, and insurance status, FM-only hospitals had an adjusted 34.3% lower rate of cesarean sections than hospitals with both FM and OB physicians (adjusted incidence rate ratio, 0.66; 95% CI, 0.52-0.98).
In addition to lower cesarean delivery rates, the study revealed that hospitals staffed exclusively by FM physicians reported a stronger safety culture, as measured by nurse perceptions of unit norms supporting vaginal birth. Nurses at FM-only hospitals were more likely to endorse safety practices that favored vaginal delivery, a finding that was statistically significant. The study also found that nurses at FM-only hospitals rated overall unit safety culture higher than those at hospitals staffed solely by OBs or a combination of FM physicians and OBs.
“I’m not surprised [by these findings],” said Joedrecka S. Brown Speights, MD, professor and chair of the Department of Family Medicine and Rural Health at Florida State University College of Medicine, Tallahassee.
She noted that the data echo previous reports demonstrating the broader benefits of FM involvement.
“When people get primary care, life is better,” Brown Speights said, citing improved outcomes, greater health equity, and lower overall healthcare costs associated with high-quality primary care.
“That’s what we need for women and for pregnant persons, especially in rural areas,” she said.
The Model Itself Could Be the Biggest Finding
According to White VanGompel, the biggest finding from the study is the existence of the team-based model itself — where FM providers lead obstetric care with support from general surgeons.
“Quite honestly, many people around the country, including family physicians like myself, did not know [this model] existed and was thriving in these rural areas that are on the verge of becoming maternity care deserts,” White VanGompel said in an interview. “That makes a huge difference clinically because those are patients that otherwise wouldn’t have access to comprehensive pregnancy care.”
This FM-led model has the added advantage of improving continuity of care, she added, noting that issues like maternal mental health — a major contributor to postpartum morbidity and mortality — are a primary care issue.
“If we are not involved in that patient’s pregnancy care, and we don’t know that they’ve had this postpartum course or they’ve had antepartum depression, it’s very hard for us to then jump in and accurately treat that person,” White VanGompel said. “If we’re involved in the entire course of care, we can make that contribution.”
Emilio A. Russo, MD, Marie Lahasky Professor of Family Medicine and chair of the Department of Family Medicine at Louisiana State University (LSU) Health Sciences Center New Orleans, and program director of the LSU Rural Family Medicine Program, Bogalusa, Louisiana, agreed that FM providers’ more continuous care, along with experience treating both mothers and babies, make them invaluable in the maternity care setting.
“We are missing the opportunity to incorporate family physicians and nurse midwives into the continuum of care for women, especially in these remote areas,” Russo said in an interview. “Family physicians and nurse midwives are the only two [groups] in the health system trained and licensed to care for both mother and baby, and I have to believe that there’s something profoundly important about that.”
Barriers May Block FM Providers From Obstetric Practice
In a recent Birth editorial, Simone Hampton, MD, of Carle Health Family Medicine, Urbana, Illinois, explored a key question: Why aren’t we using FM to help confront the maternal mortality crisis in the United States?
Hampton described how obstetric care is often siloed between specialties and barriers, including insufficient training, organizational constraints, and malpractice coverage, deter FM physicians from practicing obstetrics.
In an additional written comment, Hampton suggested that family doctors also face misconceptions about their ability to provide obstetric care, even with rigorous training and a comprehensive skill set.
“We are interested in caring for families,” Hampton said, emphasizing how FM providers are uniquely trained to care for the maternal dyad in a way that OBs are not and often view birth as a more natural process that typically does not require intervention.
Unfortunately, hospital administrators often maintain a different view, Brown Speights said, describing how some centers limit obstetric care privileges exclusively to OBs or require case volume minimums that can be tough to reach in a rural setting.
“If you have low-volume places, you can have a challenge meeting the numbers to keep up the requirements to get credentialed to practice obstetrics at the hospital,” she said, which only exacerbates gaps in maternity care access.
“This type of skill set in a rural place often, by default, represents a lower volume,” Russo said. “So how do the interests of competency and access intersect in this space?”
Generating more data to support the quality of FM-led obstetric models could be the clearest path forward, according to White VanGompel. She suggested that team-based approaches like the one described in the present study deserve further investigation in other hospital systems.
Until then, this gap in maternity care remains an ongoing, and often personal, concern.
“The more I do this quality work, the more I’m in these rooms where I’m the only family physician and I’m surrounded by all of these amazing labor and delivery nurses and obstetricians and maternal-fetal medicine doctors and midwives and doulas,” White VanGompel said. “I’m just constantly asking myself, Why am I the only family doctor in the room?”
This study was supported by the Agency for Healthcare Research and Quality and the North Shore Auxiliary. The Iowa Maternal Quality Care Collaborative is supported by a State Maternal Health Innovation award from the Health Resources and Services Administration. The investigators, Hampton and Brown Speights, disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF FAMILY MEDICINE
Humans and Carbs: A Complicated 800,000-Year Relationship
Trying to reduce your carbohydrate intake means going against nearly a million years of evolution.
Humans are among a few species with multiple copies of certain genes that help us break down starch — carbs like potatoes, beans, corn, and grains — so that we can turn it into energy our bodies can use.
However, it’s been difficult for researchers to pinpoint when in human history we acquired multiple copies of these genes because they’re in a region of the genome that’s hard to sequence.
A recent study published in Science suggests that humans may have developed multiple copies of the gene for amylase — an enzyme that’s the first step in starch digestion — over 800,000 years ago, long before the agricultural revolution. This genetic change could have helped us adapt to eating starchy foods.
The study shows how “what your ancestors ate thousands of years ago could be affecting our genetics today,” said Kelsey Jorgensen, PhD, a biological anthropologist at The University of Kansas, Lawrence, who was not involved in the study.
The double-edged sword has sharpened over all those centuries. On one hand, the human body needs and craves carbs to function. On the other hand, our modern-day consumption of carbs, especially calorie-dense/nutritionally-barren processed carbs, has long since passed “healthy.”
How Researchers Found Our Carb-Lover Gene
The enzyme amylase turns complex carbs into maltose, a sweet-tasting sugar that is made of two glucose molecules linked together. We make two kinds of amylases: Salivary amylase that breaks down carbs in our mouths and pancreatic amylase that is secreted into our small intestines.
Modern humans have multiple copies of both amylases. Past research showed that human populations with diets high in starch can have up to nine copies of the gene for salivary amylase, called AMY1.
To pinpoint when in human history we acquired multiple copies of AMY1, the new study utilized novel techniques, called optical genome mapping and long-read sequencing, to sequence and analyze the genes. They sequenced 98 modern-day samples and 68 ancient DNA samples, including one from a Siberian person who lived 45,000 years ago.
The ancient DNA data in the study allowed the researchers to track how the number of amylase genes changed over time, said George Perry, PhD, an anthropological geneticist at The Pennsylvania State University-University Park (he was not involved in the study).
Based on the sequencing, the team analyzed changes in the genes in their samples to gauge evolutionary timelines. Perry noted that this was a “very clever approach to estimating the amylase copy number mutation rate, which in turn can really help in testing evolutionary hypotheses.”
The researchers found that even before farming, hunter-gatherers had between four and eight AMY1 genes in their cells. This suggests that people across Eurasia already had a number of these genes long before they started growing crops. (Recent research indicates that Neanderthals also ate starchy foods.)
“Even archaic hominins had these [genetic] variations and that indicates that they were consuming starch,” said Feyza Yilmaz, PhD, an associate computational scientist at The Jackson Laboratory in Bar Harbor, Maine, and a lead author of the study.
However, 4000 years ago, after the agricultural revolution, the research indicates that there were even more AMY1 copies acquired. Yilmaz noted, “with the advance of agriculture, we see an increase in high amylase copy number haplotypes. So genetic variation goes hand in hand with adaptation to the environment.”
A previous study showed that species that share an environment with humans, such as dogs and pigs, also have copy number variation of amylase genes, said Yilmaz, indicating a link between genome changes and an increase in starch consumption.
Potential Health Impacts on Modern Humans
The duplications in the AMY1 gene could have allowed humans to better digest starches. And it’s conceivable that having more copies of the gene means being able to break down starches even more efficiently, and those with more copies “may be more prone to having high blood sugar, prediabetes, that sort of thing,” Jorgensen said.
Whether those with more AMY1 genes have more health risks is an active area of research. “Researchers tested whether there’s a correlation between AMY1 gene copies and diabetes or BMI [body mass index]. And so far, some studies show that there is indeed correlation, but other studies show that there is no correlation at all,” said Yilmaz.
Yilmaz pointed out that only 5 or 10% of carb digestion happens in our mouths, the rest occurs in our small intestine, plus there are many other factors involved in eating and metabolism.
“I am really looking forward to seeing studies which truly figure out the connection between AMY1 copy number and metabolic health and also what type of factors play a role in metabolic health,” said Yilmaz.
It’s also possible that having more AMY1 copies could lead to more carb cravings as the enzyme creates a type of sugar in our mouths. “Previous studies show that there’s a correlation between AMY1 copy number and also the amylase enzyme levels, so the faster we process the starch, the taste [of starches] will be sweeter,” said Yilmaz.
However, the link between cravings and copy numbers isn’t clear. And we don’t exactly know what came first — did the starch in humans’ diet lead to more copies of amylase genes, or did the copies of the amylase genes drive cravings that lead us to cultivate more carbs? We’ll need more research to find out.
How Will Today’s Processed Carbs Affect Our Genes Tomorrow?
As our diet changes to increasingly include processed carbs, what will happen to our AMY1 genes is fuzzy. “I don’t know what this could do to our genomes in the next 1000 years or more than 1000 years,” Yilmaz noted, but she said from the evidence it seems as though we may have peaked in AMY1 copies.
Jorgensen noted that this research is focused on a European population. She wonders whether the pattern of AMY1 duplication will be repeated in other populations “because the rise of starch happened first in the Middle East and then Europe and then later in the Americas,” she said.
“There’s individual variation and then there’s population-wide variation,” Jorgensen pointed out. She speculates that the historical diet of different cultures could explain population-based variations in AMY1 genes — it’s something future research could investigate. Other populations may also experience genetic changes as much of the world shifts to a more carb-heavy Western diet.
Overall, this research adds to the growing evidence that humans have a long history of loving carbs — for better and, at least over our most recent history and immediate future, for worse.
A version of this article appeared on Medscape.com.
Trying to reduce your carbohydrate intake means going against nearly a million years of evolution.
Humans are among a few species with multiple copies of certain genes that help us break down starch — carbs like potatoes, beans, corn, and grains — so that we can turn it into energy our bodies can use.
However, it’s been difficult for researchers to pinpoint when in human history we acquired multiple copies of these genes because they’re in a region of the genome that’s hard to sequence.
A recent study published in Science suggests that humans may have developed multiple copies of the gene for amylase — an enzyme that’s the first step in starch digestion — over 800,000 years ago, long before the agricultural revolution. This genetic change could have helped us adapt to eating starchy foods.
The study shows how “what your ancestors ate thousands of years ago could be affecting our genetics today,” said Kelsey Jorgensen, PhD, a biological anthropologist at The University of Kansas, Lawrence, who was not involved in the study.
The double-edged sword has sharpened over all those centuries. On one hand, the human body needs and craves carbs to function. On the other hand, our modern-day consumption of carbs, especially calorie-dense/nutritionally-barren processed carbs, has long since passed “healthy.”
How Researchers Found Our Carb-Lover Gene
The enzyme amylase turns complex carbs into maltose, a sweet-tasting sugar that is made of two glucose molecules linked together. We make two kinds of amylases: Salivary amylase that breaks down carbs in our mouths and pancreatic amylase that is secreted into our small intestines.
Modern humans have multiple copies of both amylases. Past research showed that human populations with diets high in starch can have up to nine copies of the gene for salivary amylase, called AMY1.
To pinpoint when in human history we acquired multiple copies of AMY1, the new study utilized novel techniques, called optical genome mapping and long-read sequencing, to sequence and analyze the genes. They sequenced 98 modern-day samples and 68 ancient DNA samples, including one from a Siberian person who lived 45,000 years ago.
The ancient DNA data in the study allowed the researchers to track how the number of amylase genes changed over time, said George Perry, PhD, an anthropological geneticist at The Pennsylvania State University-University Park (he was not involved in the study).
Based on the sequencing, the team analyzed changes in the genes in their samples to gauge evolutionary timelines. Perry noted that this was a “very clever approach to estimating the amylase copy number mutation rate, which in turn can really help in testing evolutionary hypotheses.”
The researchers found that even before farming, hunter-gatherers had between four and eight AMY1 genes in their cells. This suggests that people across Eurasia already had a number of these genes long before they started growing crops. (Recent research indicates that Neanderthals also ate starchy foods.)
“Even archaic hominins had these [genetic] variations and that indicates that they were consuming starch,” said Feyza Yilmaz, PhD, an associate computational scientist at The Jackson Laboratory in Bar Harbor, Maine, and a lead author of the study.
However, 4000 years ago, after the agricultural revolution, the research indicates that there were even more AMY1 copies acquired. Yilmaz noted, “with the advance of agriculture, we see an increase in high amylase copy number haplotypes. So genetic variation goes hand in hand with adaptation to the environment.”
A previous study showed that species that share an environment with humans, such as dogs and pigs, also have copy number variation of amylase genes, said Yilmaz, indicating a link between genome changes and an increase in starch consumption.
Potential Health Impacts on Modern Humans
The duplications in the AMY1 gene could have allowed humans to better digest starches. And it’s conceivable that having more copies of the gene means being able to break down starches even more efficiently, and those with more copies “may be more prone to having high blood sugar, prediabetes, that sort of thing,” Jorgensen said.
Whether those with more AMY1 genes have more health risks is an active area of research. “Researchers tested whether there’s a correlation between AMY1 gene copies and diabetes or BMI [body mass index]. And so far, some studies show that there is indeed correlation, but other studies show that there is no correlation at all,” said Yilmaz.
Yilmaz pointed out that only 5 or 10% of carb digestion happens in our mouths, the rest occurs in our small intestine, plus there are many other factors involved in eating and metabolism.
“I am really looking forward to seeing studies which truly figure out the connection between AMY1 copy number and metabolic health and also what type of factors play a role in metabolic health,” said Yilmaz.
It’s also possible that having more AMY1 copies could lead to more carb cravings as the enzyme creates a type of sugar in our mouths. “Previous studies show that there’s a correlation between AMY1 copy number and also the amylase enzyme levels, so the faster we process the starch, the taste [of starches] will be sweeter,” said Yilmaz.
However, the link between cravings and copy numbers isn’t clear. And we don’t exactly know what came first — did the starch in humans’ diet lead to more copies of amylase genes, or did the copies of the amylase genes drive cravings that lead us to cultivate more carbs? We’ll need more research to find out.
How Will Today’s Processed Carbs Affect Our Genes Tomorrow?
As our diet changes to increasingly include processed carbs, what will happen to our AMY1 genes is fuzzy. “I don’t know what this could do to our genomes in the next 1000 years or more than 1000 years,” Yilmaz noted, but she said from the evidence it seems as though we may have peaked in AMY1 copies.
Jorgensen noted that this research is focused on a European population. She wonders whether the pattern of AMY1 duplication will be repeated in other populations “because the rise of starch happened first in the Middle East and then Europe and then later in the Americas,” she said.
“There’s individual variation and then there’s population-wide variation,” Jorgensen pointed out. She speculates that the historical diet of different cultures could explain population-based variations in AMY1 genes — it’s something future research could investigate. Other populations may also experience genetic changes as much of the world shifts to a more carb-heavy Western diet.
Overall, this research adds to the growing evidence that humans have a long history of loving carbs — for better and, at least over our most recent history and immediate future, for worse.
A version of this article appeared on Medscape.com.
Trying to reduce your carbohydrate intake means going against nearly a million years of evolution.
Humans are among a few species with multiple copies of certain genes that help us break down starch — carbs like potatoes, beans, corn, and grains — so that we can turn it into energy our bodies can use.
However, it’s been difficult for researchers to pinpoint when in human history we acquired multiple copies of these genes because they’re in a region of the genome that’s hard to sequence.
A recent study published in Science suggests that humans may have developed multiple copies of the gene for amylase — an enzyme that’s the first step in starch digestion — over 800,000 years ago, long before the agricultural revolution. This genetic change could have helped us adapt to eating starchy foods.
The study shows how “what your ancestors ate thousands of years ago could be affecting our genetics today,” said Kelsey Jorgensen, PhD, a biological anthropologist at The University of Kansas, Lawrence, who was not involved in the study.
The double-edged sword has sharpened over all those centuries. On one hand, the human body needs and craves carbs to function. On the other hand, our modern-day consumption of carbs, especially calorie-dense/nutritionally-barren processed carbs, has long since passed “healthy.”
How Researchers Found Our Carb-Lover Gene
The enzyme amylase turns complex carbs into maltose, a sweet-tasting sugar that is made of two glucose molecules linked together. We make two kinds of amylases: Salivary amylase that breaks down carbs in our mouths and pancreatic amylase that is secreted into our small intestines.
Modern humans have multiple copies of both amylases. Past research showed that human populations with diets high in starch can have up to nine copies of the gene for salivary amylase, called AMY1.
To pinpoint when in human history we acquired multiple copies of AMY1, the new study utilized novel techniques, called optical genome mapping and long-read sequencing, to sequence and analyze the genes. They sequenced 98 modern-day samples and 68 ancient DNA samples, including one from a Siberian person who lived 45,000 years ago.
The ancient DNA data in the study allowed the researchers to track how the number of amylase genes changed over time, said George Perry, PhD, an anthropological geneticist at The Pennsylvania State University-University Park (he was not involved in the study).
Based on the sequencing, the team analyzed changes in the genes in their samples to gauge evolutionary timelines. Perry noted that this was a “very clever approach to estimating the amylase copy number mutation rate, which in turn can really help in testing evolutionary hypotheses.”
The researchers found that even before farming, hunter-gatherers had between four and eight AMY1 genes in their cells. This suggests that people across Eurasia already had a number of these genes long before they started growing crops. (Recent research indicates that Neanderthals also ate starchy foods.)
“Even archaic hominins had these [genetic] variations and that indicates that they were consuming starch,” said Feyza Yilmaz, PhD, an associate computational scientist at The Jackson Laboratory in Bar Harbor, Maine, and a lead author of the study.
However, 4000 years ago, after the agricultural revolution, the research indicates that there were even more AMY1 copies acquired. Yilmaz noted, “with the advance of agriculture, we see an increase in high amylase copy number haplotypes. So genetic variation goes hand in hand with adaptation to the environment.”
A previous study showed that species that share an environment with humans, such as dogs and pigs, also have copy number variation of amylase genes, said Yilmaz, indicating a link between genome changes and an increase in starch consumption.
Potential Health Impacts on Modern Humans
The duplications in the AMY1 gene could have allowed humans to better digest starches. And it’s conceivable that having more copies of the gene means being able to break down starches even more efficiently, and those with more copies “may be more prone to having high blood sugar, prediabetes, that sort of thing,” Jorgensen said.
Whether those with more AMY1 genes have more health risks is an active area of research. “Researchers tested whether there’s a correlation between AMY1 gene copies and diabetes or BMI [body mass index]. And so far, some studies show that there is indeed correlation, but other studies show that there is no correlation at all,” said Yilmaz.
Yilmaz pointed out that only 5 or 10% of carb digestion happens in our mouths, the rest occurs in our small intestine, plus there are many other factors involved in eating and metabolism.
“I am really looking forward to seeing studies which truly figure out the connection between AMY1 copy number and metabolic health and also what type of factors play a role in metabolic health,” said Yilmaz.
It’s also possible that having more AMY1 copies could lead to more carb cravings as the enzyme creates a type of sugar in our mouths. “Previous studies show that there’s a correlation between AMY1 copy number and also the amylase enzyme levels, so the faster we process the starch, the taste [of starches] will be sweeter,” said Yilmaz.
However, the link between cravings and copy numbers isn’t clear. And we don’t exactly know what came first — did the starch in humans’ diet lead to more copies of amylase genes, or did the copies of the amylase genes drive cravings that lead us to cultivate more carbs? We’ll need more research to find out.
How Will Today’s Processed Carbs Affect Our Genes Tomorrow?
As our diet changes to increasingly include processed carbs, what will happen to our AMY1 genes is fuzzy. “I don’t know what this could do to our genomes in the next 1000 years or more than 1000 years,” Yilmaz noted, but she said from the evidence it seems as though we may have peaked in AMY1 copies.
Jorgensen noted that this research is focused on a European population. She wonders whether the pattern of AMY1 duplication will be repeated in other populations “because the rise of starch happened first in the Middle East and then Europe and then later in the Americas,” she said.
“There’s individual variation and then there’s population-wide variation,” Jorgensen pointed out. She speculates that the historical diet of different cultures could explain population-based variations in AMY1 genes — it’s something future research could investigate. Other populations may also experience genetic changes as much of the world shifts to a more carb-heavy Western diet.
Overall, this research adds to the growing evidence that humans have a long history of loving carbs — for better and, at least over our most recent history and immediate future, for worse.
A version of this article appeared on Medscape.com.