It’s not unusual for physicians to see other doctors as patients – often they’re colleagues or even friends. That relationship can influence their behavior and how they treat the physician-patient, which may have unintended consequences for both of them.

“When doctors don’t get the proper care, that’s when things go south. Any time physicians lower their standard of care, there is a risk of missing something that could affect their differential diagnosis, ultimate working diagnosis, and treatment plan,” said Michael Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn, who saw only medical students, physicians, and their family members in his private practice for over 3 decades.

Of the more than 200 physicians who responded to a recent Medscape poll, more than half said they treated physician-patients differently from other patients.

They granted their peers special privileges: They spent more time with them than other patients, gave out their personal contact information, and granted them professional courtesy by waiving or discounting their fees.

Published studies have reported that special treatment of physician-patients, such as giving personal contact information or avoiding uncomfortable testing, can create challenges for the treating physicians who may feel pressure to deviate from the standard of care.

The American Medical Association has recognized the challenges that physicians have when they treat other physicians they know personally or professionally, including a potential loss of objectivity, privacy, or confidentiality.

The AMA recommends that physicians treat physician-patients the same way they would other patients. The guidance states that the treating physician should exercise objective professional judgment and make unbiased treatment recommendations; be sensitive to the potential psychological discomfort of the physician-patient, and respect the physical and informational privacy of physician-patients.

Dr. Myers recalled that one doctor-patient said his primary care physician was his business partner in the practice. They ordered tests for each other and occasionally examined each other, but the patient never felt comfortable asking his partner for a full physical, said Dr. Myers, the author of “Becoming a Doctors’ Doctor: A Memoir.”

“I recommended that he choose a primary care doctor whom he didn’t know so that he could truly be a patient and the doctor could truly be a treating doctor,” said Dr. Myers.

Physician-patients may also be concerned about running into their physicians and being judged, or that they will break confidentiality and tell their spouse or another colleague, said Dr. Myers.

“When your doctor is a complete and total stranger, and especially if you live in a sizable community and your paths never cross, you don’t have that added worry,” he said.
 

Do docs expect special treatment as patients?

Some doctors expect special treatment from other doctors when they’re patients – 14% of physician poll respondents said that was their experience.

Dr. Myers recommends setting boundaries with doctor-patients early on in the relationship. “Some doctors expected me to go over my regular appointment time and when they realized that I started and stopped on time, they got upset. Once, one doctor insisted to my answering service that he had to talk to me although I was at home. When he started talking, I interrupted him and asked if the matter was urgent. He said no, so I offered to fit him in before his next appointment if he felt it couldn’t wait,” said Dr. Myers.

Some doctors also give physician-patients “professional courtesy” when it comes to payment. One in four poll respondents said they waived or discounted their professional fees for a doctor-patient. As most doctors have health insurance, doctors may waive copayments or other out-of-pocket fees, according to the American Academy of Pediatrics.

However, waiving or discounting health insurance fees, especially for government funded insurance, may be illegal under federal anti-fraud and abuse laws and payer contracts as well as state laws, the AAP says. It’s best to check with an attorney.
 

Treating other physicians can be rewarding

“Physicians can be the most rewarding patients because they are allies and partners in the effort to overcome whatever is ailing them,” said one doctor who responded to the Medscape poll.

Over two-thirds of respondents said that doctor-patients participated much more in their care than did other patients – typically, they discussed their care in more depth than did other patients.

Most doctors also felt that it was easier to communicate with their physician-patients than other patients because they understood medicine and were knowledgeable about their conditions.
 

Being judged by your peers can be stressful

How physicians feel about treating physician-patients is complicated. Nearly half of respondents said that it was more stressful than treating other patients.

One respondent said, “If we are honest, treating other physicians as patients is more stressful because we know that our skills are being assessed by someone who is at our level. There is no training for treating physicians, as there is for the Pope’s confessor. And we can be challenging in more ways than one!”

About one-third of poll respondents said they were afraid of disappointing their physician-patients.

“I’m not surprised,” said Dr. Myers, when told of that poll response. “This is why some doctors are reluctant to treat other physicians; they may wonder whether they’re up to speed. I have always thrived on having a high bar set for me – it spurs me on to really stay current with the literature and be humble,” he said.

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

It’s not unusual for physicians to see other doctors as patients – often they’re colleagues or even friends. That relationship can influence their behavior and how they treat the physician-patient, which may have unintended consequences for both of them.

“When doctors don’t get the proper care, that’s when things go south. Any time physicians lower their standard of care, there is a risk of missing something that could affect their differential diagnosis, ultimate working diagnosis, and treatment plan,” said Michael Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn, who saw only medical students, physicians, and their family members in his private practice for over 3 decades.

Of the more than 200 physicians who responded to a recent Medscape poll, more than half said they treated physician-patients differently from other patients.

They granted their peers special privileges: They spent more time with them than other patients, gave out their personal contact information, and granted them professional courtesy by waiving or discounting their fees.

Published studies have reported that special treatment of physician-patients, such as giving personal contact information or avoiding uncomfortable testing, can create challenges for the treating physicians who may feel pressure to deviate from the standard of care.

The American Medical Association has recognized the challenges that physicians have when they treat other physicians they know personally or professionally, including a potential loss of objectivity, privacy, or confidentiality.

The AMA recommends that physicians treat physician-patients the same way they would other patients. The guidance states that the treating physician should exercise objective professional judgment and make unbiased treatment recommendations; be sensitive to the potential psychological discomfort of the physician-patient, and respect the physical and informational privacy of physician-patients.

Dr. Myers recalled that one doctor-patient said his primary care physician was his business partner in the practice. They ordered tests for each other and occasionally examined each other, but the patient never felt comfortable asking his partner for a full physical, said Dr. Myers, the author of “Becoming a Doctors’ Doctor: A Memoir.”

“I recommended that he choose a primary care doctor whom he didn’t know so that he could truly be a patient and the doctor could truly be a treating doctor,” said Dr. Myers.

Physician-patients may also be concerned about running into their physicians and being judged, or that they will break confidentiality and tell their spouse or another colleague, said Dr. Myers.

“When your doctor is a complete and total stranger, and especially if you live in a sizable community and your paths never cross, you don’t have that added worry,” he said.
 

Do docs expect special treatment as patients?

Some doctors expect special treatment from other doctors when they’re patients – 14% of physician poll respondents said that was their experience.

Dr. Myers recommends setting boundaries with doctor-patients early on in the relationship. “Some doctors expected me to go over my regular appointment time and when they realized that I started and stopped on time, they got upset. Once, one doctor insisted to my answering service that he had to talk to me although I was at home. When he started talking, I interrupted him and asked if the matter was urgent. He said no, so I offered to fit him in before his next appointment if he felt it couldn’t wait,” said Dr. Myers.

Some doctors also give physician-patients “professional courtesy” when it comes to payment. One in four poll respondents said they waived or discounted their professional fees for a doctor-patient. As most doctors have health insurance, doctors may waive copayments or other out-of-pocket fees, according to the American Academy of Pediatrics.

However, waiving or discounting health insurance fees, especially for government funded insurance, may be illegal under federal anti-fraud and abuse laws and payer contracts as well as state laws, the AAP says. It’s best to check with an attorney.
 

Treating other physicians can be rewarding

“Physicians can be the most rewarding patients because they are allies and partners in the effort to overcome whatever is ailing them,” said one doctor who responded to the Medscape poll.

Over two-thirds of respondents said that doctor-patients participated much more in their care than did other patients – typically, they discussed their care in more depth than did other patients.

Most doctors also felt that it was easier to communicate with their physician-patients than other patients because they understood medicine and were knowledgeable about their conditions.
 

Being judged by your peers can be stressful

How physicians feel about treating physician-patients is complicated. Nearly half of respondents said that it was more stressful than treating other patients.

One respondent said, “If we are honest, treating other physicians as patients is more stressful because we know that our skills are being assessed by someone who is at our level. There is no training for treating physicians, as there is for the Pope’s confessor. And we can be challenging in more ways than one!”

About one-third of poll respondents said they were afraid of disappointing their physician-patients.

“I’m not surprised,” said Dr. Myers, when told of that poll response. “This is why some doctors are reluctant to treat other physicians; they may wonder whether they’re up to speed. I have always thrived on having a high bar set for me – it spurs me on to really stay current with the literature and be humble,” he said.

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

It’s not unusual for physicians to see other doctors as patients – often they’re colleagues or even friends. That relationship can influence their behavior and how they treat the physician-patient, which may have unintended consequences for both of them.

“When doctors don’t get the proper care, that’s when things go south. Any time physicians lower their standard of care, there is a risk of missing something that could affect their differential diagnosis, ultimate working diagnosis, and treatment plan,” said Michael Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn, who saw only medical students, physicians, and their family members in his private practice for over 3 decades.

Of the more than 200 physicians who responded to a recent Medscape poll, more than half said they treated physician-patients differently from other patients.

They granted their peers special privileges: They spent more time with them than other patients, gave out their personal contact information, and granted them professional courtesy by waiving or discounting their fees.

Published studies have reported that special treatment of physician-patients, such as giving personal contact information or avoiding uncomfortable testing, can create challenges for the treating physicians who may feel pressure to deviate from the standard of care.

The American Medical Association has recognized the challenges that physicians have when they treat other physicians they know personally or professionally, including a potential loss of objectivity, privacy, or confidentiality.

The AMA recommends that physicians treat physician-patients the same way they would other patients. The guidance states that the treating physician should exercise objective professional judgment and make unbiased treatment recommendations; be sensitive to the potential psychological discomfort of the physician-patient, and respect the physical and informational privacy of physician-patients.

Dr. Myers recalled that one doctor-patient said his primary care physician was his business partner in the practice. They ordered tests for each other and occasionally examined each other, but the patient never felt comfortable asking his partner for a full physical, said Dr. Myers, the author of “Becoming a Doctors’ Doctor: A Memoir.”

“I recommended that he choose a primary care doctor whom he didn’t know so that he could truly be a patient and the doctor could truly be a treating doctor,” said Dr. Myers.

Physician-patients may also be concerned about running into their physicians and being judged, or that they will break confidentiality and tell their spouse or another colleague, said Dr. Myers.

“When your doctor is a complete and total stranger, and especially if you live in a sizable community and your paths never cross, you don’t have that added worry,” he said.
 

Do docs expect special treatment as patients?

Some doctors expect special treatment from other doctors when they’re patients – 14% of physician poll respondents said that was their experience.

Dr. Myers recommends setting boundaries with doctor-patients early on in the relationship. “Some doctors expected me to go over my regular appointment time and when they realized that I started and stopped on time, they got upset. Once, one doctor insisted to my answering service that he had to talk to me although I was at home. When he started talking, I interrupted him and asked if the matter was urgent. He said no, so I offered to fit him in before his next appointment if he felt it couldn’t wait,” said Dr. Myers.

Some doctors also give physician-patients “professional courtesy” when it comes to payment. One in four poll respondents said they waived or discounted their professional fees for a doctor-patient. As most doctors have health insurance, doctors may waive copayments or other out-of-pocket fees, according to the American Academy of Pediatrics.

However, waiving or discounting health insurance fees, especially for government funded insurance, may be illegal under federal anti-fraud and abuse laws and payer contracts as well as state laws, the AAP says. It’s best to check with an attorney.
 

Treating other physicians can be rewarding

“Physicians can be the most rewarding patients because they are allies and partners in the effort to overcome whatever is ailing them,” said one doctor who responded to the Medscape poll.

Over two-thirds of respondents said that doctor-patients participated much more in their care than did other patients – typically, they discussed their care in more depth than did other patients.

Most doctors also felt that it was easier to communicate with their physician-patients than other patients because they understood medicine and were knowledgeable about their conditions.
 

Being judged by your peers can be stressful

How physicians feel about treating physician-patients is complicated. Nearly half of respondents said that it was more stressful than treating other patients.

One respondent said, “If we are honest, treating other physicians as patients is more stressful because we know that our skills are being assessed by someone who is at our level. There is no training for treating physicians, as there is for the Pope’s confessor. And we can be challenging in more ways than one!”

About one-third of poll respondents said they were afraid of disappointing their physician-patients.

“I’m not surprised,” said Dr. Myers, when told of that poll response. “This is why some doctors are reluctant to treat other physicians; they may wonder whether they’re up to speed. I have always thrived on having a high bar set for me – it spurs me on to really stay current with the literature and be humble,” he said.

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

At a routine doctor’s visit, a member of the clinic staff takes digital pictures of a patient’s retinas.

Within seconds, an artificial intelligence (AI) algorithm determines if the patient has diabetic retinopathy, a complication of diabetes that can lead to blindness.

If they do, the physician refers the patient to an eye care specialist for further evaluation and treatment.

This scene already is playing out in primary care clinics around the United States and in other countries, and it may become more common.

Health care systems intend to expand their use of AI to screen for diabetic retinopathy in 2023, and companies are developing more algorithms for this purpose.

In May, OSF HealthCare, a network of medical facilities headquartered in Peoria, Ill., piloted an AI system to diagnose diabetic retinopathy, a condition that affects an estimated 4 million Americans. In 2023, the health care system plans to expand the technology to 34 locations.

Meanwhile, the Food and Drug Administration in November approved a new AI system to diagnose diabetic retinopathy, making AEYE-DS from AEYE Health the third such product on the market.

Roomasa Channa, MD, a clinician-scientist with the McPherson Eye Research Institute at the University of Wisconsin–Madison, has studied the use of AI in teenage patients with diabetes. She said she soon plans to use AI screening in federally qualified health centers to screen adults with diabetes.

Dr. Channa welcomed the latest regulatory clearance and said she hopes another Food and Drug Administration–cleared algorithm product will improve accessibility to the technology.

“It is good to see more players in the field: We need this technology to be readily available and affordable,” she said in an interview.
 

A mixed reception

Responses from physicians to this type of AI have been mixed. Some worry, for instance, that the algorithms might be programmed with unrecognized biases that could lead them to less accurately interpret images from certain patient groups. Researchers should be on the lookout out for this possibility, Dr. Channa said.

“We need more real-world studies in different settings,” she said. “We also need to keep collecting data on AI performance post approval,” like investigators do for newly approved drugs.

The first AI system to diagnose diabetic retinopathy, IDx-DR, was approved by the FDA in 2018 and rolled out in retail clinics soon after. A second system, EyeArt, gained clearance by the agency in 2020.

Adding AI algorithms into primary care practice has changed how patients with diabetes can receive a screening. It also has introduced a new way for certain medical conditions to be diagnosed in primary care.

The American Medical Association in 2021 released a new CPT code to allow clinicians to bill government and private insurers for use of these services. CPT code 92229 refers to imaging of the retina to detect disease with an automated analysis and report at the point of care.
 

Meeting a need

Health care clinics in underserved areas often do not have eye care providers onsite to conduct recommended screening exams, so AI could help patients receive screening who otherwise would not get it, Dr. Channa said.

Dr. Channa and colleagues successfully used one AI system, IDx-DR, to screen children at a pediatric diabetes clinic. Over a year, screening rates jumped from 49% to 95%.

This technology “can potentially help us in decreasing disparities in care and focusing our efforts on patients with the most severe diseases,” she said.

OSF HealthCare recently obtained an approximately $1 million grant from drug company Regeneron to expand the use of AI-based screening for diabetic retinopathy, following a successful pilot. Regeneron markets a treatment for diabetic retinopathy.

Without an AI option, recommended eye screening for patients with diabetes often falls through the cracks, according to Mark Meeker, DO, vice president of community medicine at OSF. Primary care physicians may refer patients elsewhere for their annual retinopathy screening exam.

“That often doesn’t get completed because it’s another trip, another appointment, another time away from work,” Dr. Meeker said.

All patients with diabetes should have their eyes screened each year, but between one- to two-thirds of patients nationwide do not, he said.

A member of the clinic staff takes digital pictures of the retina, almost always through undilated pupils.

If the result is normal, the patient is scheduled for another follow-up screening in a year. If early signs of diabetic retinopathy are spotted, patients are referred to an eye care specialist.

After 7 months of the pilot program, OSF had screened about 350 patients. Approximately 20% had diabetic retinopathy, according to OSF.
 

‘A huge impact’

OSF has about 66,000 patients with diabetes. About two-thirds do not receive annual screening, Dr. Meeker estimated. “This can have a huge impact on the quality of life in the coming years for our diabetic patients. It’s pretty profound.”

Eye care specialists typically treat diabetic retinopathy with lasers, surgery, or medication. For primary care clinicians, however, AI screening for retinopathy is an opportunity to emphasize how important it is to manage the disease and what its consequences can be.

AI screening is “another tool for us to use to get patients more engaged in their own care,” Dr. Meeker said. “This is probably the biggest advance in AI affecting our day-to-day interaction with patients that we’ve seen in primary care.”
 

A business opportunity, too?

The IDx-DR platform OSF is using in its clinics is owned by the company Digital Diagnostics. OSF Ventures, an investment arm of OSF HealthCare, has invested in the company, the health care system announced in August.

Other companies have had their products used in practice. In 2019, for example, Eyenuk described how its EyeArt system had been used to screen thousands of patients in Germany and in Italy.

And in 2021, Eyenuk reported that its customer base in the United States had expanded to more than 25 locations. The company credited a Centers for Medicare & Medicaid Services plan to cover CPT code 92229 with supporting this growth.

Zack Dvey-Aharon, PhD, the CEO of AEYE Health, said the company was motivated to enter this space when regulators decided that AI could be used to diagnose a condition — not just as a tool to help doctors arrive at a diagnosis.

With proper training, a person can diagnose diabetic retinopathy relatively easily if the image of the retina is of excellent quality. If image is dark or blurry, however, it’s a different story.

AI has its advantages in this scenario, according to Dr. Dvey-Aharon. “For AI, those darker, more blurry images are actually highly readable with fantastic accuracy.”
 

More to come?

The possibilities of AI in analyzing retinal images are vast.

New research shows that AI may be able to detect Alzheimer’s disease or predict a person’s risk for heart attack and stroke based on snapshots of the retina.

The retina may also shed light on kidney disease, control of blood glucose and blood pressure, hepatobiliary disease, and coronary artery calcium, according to Eric J. Topol, MD, director of Scripps Research Translational Institute in La Jolla, Calif.

Beyond retinas, interpretation of electrocardiograms (ECGs) may be another frontier for AI in primary care. In one trial, an AI-enhanced ECG reading facilitated early diagnosis of low ejection fraction, and some doctors now receive these reports routinely, Dr. Topol wrote.

The potential value of AI in medicine “extends to virtually all forms of medical images that have been assessed to date,” Dr. Topol wrote on his “Ground Truths” Substack.

Although much of the focus has been on what AI can see, researchers also are exploring what AI can do with what it hears. Early research suggests that algorithms may be able to diagnose disease by analyzing patients’ voices.

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

At a routine doctor’s visit, a member of the clinic staff takes digital pictures of a patient’s retinas.

Within seconds, an artificial intelligence (AI) algorithm determines if the patient has diabetic retinopathy, a complication of diabetes that can lead to blindness.

If they do, the physician refers the patient to an eye care specialist for further evaluation and treatment.

This scene already is playing out in primary care clinics around the United States and in other countries, and it may become more common.

Health care systems intend to expand their use of AI to screen for diabetic retinopathy in 2023, and companies are developing more algorithms for this purpose.

In May, OSF HealthCare, a network of medical facilities headquartered in Peoria, Ill., piloted an AI system to diagnose diabetic retinopathy, a condition that affects an estimated 4 million Americans. In 2023, the health care system plans to expand the technology to 34 locations.

Meanwhile, the Food and Drug Administration in November approved a new AI system to diagnose diabetic retinopathy, making AEYE-DS from AEYE Health the third such product on the market.

Roomasa Channa, MD, a clinician-scientist with the McPherson Eye Research Institute at the University of Wisconsin–Madison, has studied the use of AI in teenage patients with diabetes. She said she soon plans to use AI screening in federally qualified health centers to screen adults with diabetes.

Dr. Channa welcomed the latest regulatory clearance and said she hopes another Food and Drug Administration–cleared algorithm product will improve accessibility to the technology.

“It is good to see more players in the field: We need this technology to be readily available and affordable,” she said in an interview.
 

A mixed reception

Responses from physicians to this type of AI have been mixed. Some worry, for instance, that the algorithms might be programmed with unrecognized biases that could lead them to less accurately interpret images from certain patient groups. Researchers should be on the lookout out for this possibility, Dr. Channa said.

“We need more real-world studies in different settings,” she said. “We also need to keep collecting data on AI performance post approval,” like investigators do for newly approved drugs.

The first AI system to diagnose diabetic retinopathy, IDx-DR, was approved by the FDA in 2018 and rolled out in retail clinics soon after. A second system, EyeArt, gained clearance by the agency in 2020.

Adding AI algorithms into primary care practice has changed how patients with diabetes can receive a screening. It also has introduced a new way for certain medical conditions to be diagnosed in primary care.

The American Medical Association in 2021 released a new CPT code to allow clinicians to bill government and private insurers for use of these services. CPT code 92229 refers to imaging of the retina to detect disease with an automated analysis and report at the point of care.
 

Meeting a need

Health care clinics in underserved areas often do not have eye care providers onsite to conduct recommended screening exams, so AI could help patients receive screening who otherwise would not get it, Dr. Channa said.

Dr. Channa and colleagues successfully used one AI system, IDx-DR, to screen children at a pediatric diabetes clinic. Over a year, screening rates jumped from 49% to 95%.

This technology “can potentially help us in decreasing disparities in care and focusing our efforts on patients with the most severe diseases,” she said.

OSF HealthCare recently obtained an approximately $1 million grant from drug company Regeneron to expand the use of AI-based screening for diabetic retinopathy, following a successful pilot. Regeneron markets a treatment for diabetic retinopathy.

Without an AI option, recommended eye screening for patients with diabetes often falls through the cracks, according to Mark Meeker, DO, vice president of community medicine at OSF. Primary care physicians may refer patients elsewhere for their annual retinopathy screening exam.

“That often doesn’t get completed because it’s another trip, another appointment, another time away from work,” Dr. Meeker said.

All patients with diabetes should have their eyes screened each year, but between one- to two-thirds of patients nationwide do not, he said.

A member of the clinic staff takes digital pictures of the retina, almost always through undilated pupils.

If the result is normal, the patient is scheduled for another follow-up screening in a year. If early signs of diabetic retinopathy are spotted, patients are referred to an eye care specialist.

After 7 months of the pilot program, OSF had screened about 350 patients. Approximately 20% had diabetic retinopathy, according to OSF.
 

‘A huge impact’

OSF has about 66,000 patients with diabetes. About two-thirds do not receive annual screening, Dr. Meeker estimated. “This can have a huge impact on the quality of life in the coming years for our diabetic patients. It’s pretty profound.”

Eye care specialists typically treat diabetic retinopathy with lasers, surgery, or medication. For primary care clinicians, however, AI screening for retinopathy is an opportunity to emphasize how important it is to manage the disease and what its consequences can be.

AI screening is “another tool for us to use to get patients more engaged in their own care,” Dr. Meeker said. “This is probably the biggest advance in AI affecting our day-to-day interaction with patients that we’ve seen in primary care.”
 

A business opportunity, too?

The IDx-DR platform OSF is using in its clinics is owned by the company Digital Diagnostics. OSF Ventures, an investment arm of OSF HealthCare, has invested in the company, the health care system announced in August.

Other companies have had their products used in practice. In 2019, for example, Eyenuk described how its EyeArt system had been used to screen thousands of patients in Germany and in Italy.

And in 2021, Eyenuk reported that its customer base in the United States had expanded to more than 25 locations. The company credited a Centers for Medicare & Medicaid Services plan to cover CPT code 92229 with supporting this growth.

Zack Dvey-Aharon, PhD, the CEO of AEYE Health, said the company was motivated to enter this space when regulators decided that AI could be used to diagnose a condition — not just as a tool to help doctors arrive at a diagnosis.

With proper training, a person can diagnose diabetic retinopathy relatively easily if the image of the retina is of excellent quality. If image is dark or blurry, however, it’s a different story.

AI has its advantages in this scenario, according to Dr. Dvey-Aharon. “For AI, those darker, more blurry images are actually highly readable with fantastic accuracy.”
 

More to come?

The possibilities of AI in analyzing retinal images are vast.

New research shows that AI may be able to detect Alzheimer’s disease or predict a person’s risk for heart attack and stroke based on snapshots of the retina.

The retina may also shed light on kidney disease, control of blood glucose and blood pressure, hepatobiliary disease, and coronary artery calcium, according to Eric J. Topol, MD, director of Scripps Research Translational Institute in La Jolla, Calif.

Beyond retinas, interpretation of electrocardiograms (ECGs) may be another frontier for AI in primary care. In one trial, an AI-enhanced ECG reading facilitated early diagnosis of low ejection fraction, and some doctors now receive these reports routinely, Dr. Topol wrote.

The potential value of AI in medicine “extends to virtually all forms of medical images that have been assessed to date,” Dr. Topol wrote on his “Ground Truths” Substack.

Although much of the focus has been on what AI can see, researchers also are exploring what AI can do with what it hears. Early research suggests that algorithms may be able to diagnose disease by analyzing patients’ voices.

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

At a routine doctor’s visit, a member of the clinic staff takes digital pictures of a patient’s retinas.

Within seconds, an artificial intelligence (AI) algorithm determines if the patient has diabetic retinopathy, a complication of diabetes that can lead to blindness.

If they do, the physician refers the patient to an eye care specialist for further evaluation and treatment.

This scene already is playing out in primary care clinics around the United States and in other countries, and it may become more common.

Health care systems intend to expand their use of AI to screen for diabetic retinopathy in 2023, and companies are developing more algorithms for this purpose.

In May, OSF HealthCare, a network of medical facilities headquartered in Peoria, Ill., piloted an AI system to diagnose diabetic retinopathy, a condition that affects an estimated 4 million Americans. In 2023, the health care system plans to expand the technology to 34 locations.

Meanwhile, the Food and Drug Administration in November approved a new AI system to diagnose diabetic retinopathy, making AEYE-DS from AEYE Health the third such product on the market.

Roomasa Channa, MD, a clinician-scientist with the McPherson Eye Research Institute at the University of Wisconsin–Madison, has studied the use of AI in teenage patients with diabetes. She said she soon plans to use AI screening in federally qualified health centers to screen adults with diabetes.

Dr. Channa welcomed the latest regulatory clearance and said she hopes another Food and Drug Administration–cleared algorithm product will improve accessibility to the technology.

“It is good to see more players in the field: We need this technology to be readily available and affordable,” she said in an interview.
 

A mixed reception

Responses from physicians to this type of AI have been mixed. Some worry, for instance, that the algorithms might be programmed with unrecognized biases that could lead them to less accurately interpret images from certain patient groups. Researchers should be on the lookout out for this possibility, Dr. Channa said.

“We need more real-world studies in different settings,” she said. “We also need to keep collecting data on AI performance post approval,” like investigators do for newly approved drugs.

The first AI system to diagnose diabetic retinopathy, IDx-DR, was approved by the FDA in 2018 and rolled out in retail clinics soon after. A second system, EyeArt, gained clearance by the agency in 2020.

Adding AI algorithms into primary care practice has changed how patients with diabetes can receive a screening. It also has introduced a new way for certain medical conditions to be diagnosed in primary care.

The American Medical Association in 2021 released a new CPT code to allow clinicians to bill government and private insurers for use of these services. CPT code 92229 refers to imaging of the retina to detect disease with an automated analysis and report at the point of care.
 

Meeting a need

Health care clinics in underserved areas often do not have eye care providers onsite to conduct recommended screening exams, so AI could help patients receive screening who otherwise would not get it, Dr. Channa said.

Dr. Channa and colleagues successfully used one AI system, IDx-DR, to screen children at a pediatric diabetes clinic. Over a year, screening rates jumped from 49% to 95%.

This technology “can potentially help us in decreasing disparities in care and focusing our efforts on patients with the most severe diseases,” she said.

OSF HealthCare recently obtained an approximately $1 million grant from drug company Regeneron to expand the use of AI-based screening for diabetic retinopathy, following a successful pilot. Regeneron markets a treatment for diabetic retinopathy.

Without an AI option, recommended eye screening for patients with diabetes often falls through the cracks, according to Mark Meeker, DO, vice president of community medicine at OSF. Primary care physicians may refer patients elsewhere for their annual retinopathy screening exam.

“That often doesn’t get completed because it’s another trip, another appointment, another time away from work,” Dr. Meeker said.

All patients with diabetes should have their eyes screened each year, but between one- to two-thirds of patients nationwide do not, he said.

A member of the clinic staff takes digital pictures of the retina, almost always through undilated pupils.

If the result is normal, the patient is scheduled for another follow-up screening in a year. If early signs of diabetic retinopathy are spotted, patients are referred to an eye care specialist.

After 7 months of the pilot program, OSF had screened about 350 patients. Approximately 20% had diabetic retinopathy, according to OSF.
 

‘A huge impact’

OSF has about 66,000 patients with diabetes. About two-thirds do not receive annual screening, Dr. Meeker estimated. “This can have a huge impact on the quality of life in the coming years for our diabetic patients. It’s pretty profound.”

Eye care specialists typically treat diabetic retinopathy with lasers, surgery, or medication. For primary care clinicians, however, AI screening for retinopathy is an opportunity to emphasize how important it is to manage the disease and what its consequences can be.

AI screening is “another tool for us to use to get patients more engaged in their own care,” Dr. Meeker said. “This is probably the biggest advance in AI affecting our day-to-day interaction with patients that we’ve seen in primary care.”
 

A business opportunity, too?

The IDx-DR platform OSF is using in its clinics is owned by the company Digital Diagnostics. OSF Ventures, an investment arm of OSF HealthCare, has invested in the company, the health care system announced in August.

Other companies have had their products used in practice. In 2019, for example, Eyenuk described how its EyeArt system had been used to screen thousands of patients in Germany and in Italy.

And in 2021, Eyenuk reported that its customer base in the United States had expanded to more than 25 locations. The company credited a Centers for Medicare & Medicaid Services plan to cover CPT code 92229 with supporting this growth.

Zack Dvey-Aharon, PhD, the CEO of AEYE Health, said the company was motivated to enter this space when regulators decided that AI could be used to diagnose a condition — not just as a tool to help doctors arrive at a diagnosis.

With proper training, a person can diagnose diabetic retinopathy relatively easily if the image of the retina is of excellent quality. If image is dark or blurry, however, it’s a different story.

AI has its advantages in this scenario, according to Dr. Dvey-Aharon. “For AI, those darker, more blurry images are actually highly readable with fantastic accuracy.”
 

More to come?

The possibilities of AI in analyzing retinal images are vast.

New research shows that AI may be able to detect Alzheimer’s disease or predict a person’s risk for heart attack and stroke based on snapshots of the retina.

The retina may also shed light on kidney disease, control of blood glucose and blood pressure, hepatobiliary disease, and coronary artery calcium, according to Eric J. Topol, MD, director of Scripps Research Translational Institute in La Jolla, Calif.

Beyond retinas, interpretation of electrocardiograms (ECGs) may be another frontier for AI in primary care. In one trial, an AI-enhanced ECG reading facilitated early diagnosis of low ejection fraction, and some doctors now receive these reports routinely, Dr. Topol wrote.

The potential value of AI in medicine “extends to virtually all forms of medical images that have been assessed to date,” Dr. Topol wrote on his “Ground Truths” Substack.

Although much of the focus has been on what AI can see, researchers also are exploring what AI can do with what it hears. Early research suggests that algorithms may be able to diagnose disease by analyzing patients’ voices.

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

Much attention has been given recently to the idea of detecting many different types of cancer from a single blood test, and a new test claiming to do that has just been reported.

The leader in this field is the Galleri test (from GRAIL) which is already in clinical use in some health care networks across the United States. That test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA (cfDNA) in a blood sample.

The new test, under development by Swedish biotechnology company Elypta AB, has a different premise. It can detect 14 cancer types based on the analysis of glycosaminoglycans, which are a diverse group of polysaccharides that are altered by the presence of tumors. Using plasma and urine samples, the method had a 41.6%-62.3% sensitivity for detecting stage I cancer at 95% specificity.

In comparison, say the authors, other assays have reported 39%-73% sensitivity to stage I cancers, but these estimates are usually limited to 12 cancer types that are considered “high-signal,” and the assays perform poorly in cancers that emit little cfDNA, such as genitourinary and brain malignancies.

“The main advantage of glycosaminoglycans appears to be that they change in the blood and urine at the earliest stages of cancer,” said study author Francesco Gatto, PhD, founder and chief scientific officer at Elypta. “Consequently, this method showed an impressive detection rate in stage I compared to other emerging methods.”

The study was published online in Proceedings of the National Academy of Sciences.


 

Combine tests?

Dr. Gatto commented that he “could envision that one day we may be able to combine these methods.”

“The same blood specimen could be used to test both glycosaminoglycans and genomic biomarkers,” said Dr. Gatto. “This strategy could hopefully detect even more cancers than with either method alone, and the resulting performance may well be sufficient as a one-stop-shop screening program.”

So how does the new test from Elypta compare with the Galleri test?

“Galleri and similar methods mostly focused on information coming from molecules of DNA naturally floating in the blood,” explained Dr. Gatto. “It makes sense to conduct research there because cancers typically start with events in the DNA.”

He noted that the current study explored a new layer of information, molecules called glycosaminoglycans, that participate in the metabolism of cancer.

“This method detected many cancers that the previous methods missed, and a substantial proportion of these were at stage I,” said Dr. Gatto. “Cancer is a complex disease, so the most layers of information we can probe noninvasively, say with a blood test, the more likely we can catch more cancers at its earliest stage.”

Other platforms typically rely on sequencing and detecting cancer-derived fractions of cfDNA, but these methods have challenges that can interfere with their usage. For example, some cancer types do not shed sufficient cfDNA and it cannot be accurately measured.

“An advantage on focusing on glycosaminoglycans is that the method does not require next-generation sequencing or similarly complex assays because glycosaminoglycans are informative with less than 10 simultaneous measurements as opposed to Galleri that looks at over 1 million DNA methylation sites,” he said.

“This makes the assay behind the test much cheaper and robust – we estimated a 5-10 times lower cost difference,” Dr. Gatto said.
 

Prospective and comparative data needed

In a comment, Eric Klein, MD, emeritus chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic explained that the “only accurate way to know how a test will perform in an intended-use population is to actually test it in that population. It’s not possible to extrapolate results directly from a case-control study.”

Cancers shed many different biologic markers into body fluids, but which of these signals will be best to serve as the basis of an MCED (multi-cancer detection test) that has clinical utility in a screening population has yet to be determined, he noted. “And it’s possible that no single test will be optimum for every clinical situation.”

“The results of this study appear promising, but it is not possible to claim superiority of one test over another based on individual case-control studies because of uncontrolled differences in the selected populations,” Dr. Klein continued. “The only scientifically accurate way to do this is to perform different tests on the same patient samples in a head-to-head comparison.”

There is only one study that he is aware of that has done this recently, in which multiple different assays looking at various signals in cell-free DNA were directly compared on the same samples (Cancer cell. 2022;40:1537-49.e12). “A targeted methylation assay that is the basis for Galleri was best for the lowest limit of detection and for predicting cancer site of origin,” said Dr. Klein.

Another expert agreed that a direct head-to-head study is needed to compare assays. “Based on this data, you cannot say that this method is better than the other one because that requires a comparative study,” said Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology, Tisch Cancer Institute at Mount Sinai, New York.

Metabolomics is interesting, and the data are encouraging, he continued. “But this is a multicancer early detection test and metabolism changes may vary from cancer type to cancer type. I’m not sure that the metabolism of lung cancer is the same as that of a gynecologic cancer.”

Dr. Hirsch also pointed out that there could also be confounding factors. “They have excluded inflammatory disease, but there can be other variables such as smoking,” he said. “Overall it gives some interesting perspectives but I would like to see more prospective validation and studies in specific disease groups, and eventually comparative studies with other methodologies.”
 

Study details

The authors evaluated if plasma and urine free GAGomes (free glycosaminoglycan profiles) deviated from baseline physiological levels in 14 cancer types and could serve as metabolic cancer biomarkers. They also then validated using free GAGomes for MCED in an external population with 2,064 samples obtained from 1,260 patients with cancer and healthy individuals.

In an in vivo cancer progression model, they observed widespread cancer-specific changes in biofluidic free GAGomes and then developed three machine-learning models based on urine (n_urine = 220 cancer vs. 360 healthy) and plasma (n_plasma = 517 cancer vs. 425 healthy) free GAGomes that were able to detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 (with up to 62% sensitivity to stage I disease at 95% specificity).

To assess if altered GAGome features associated with cancer suggested more aggressive tumor biology, they correlated each score with overall survival. The median follow-up time was 17 months in the plasma cohort (n = 370 across 13 cancer types), 15 months in the urine cohort (n = 162 across 4 cancer types), and 15 months in the combined cohort (n = 152 across 4 cancer types).

They found that all three scores independently predicted overall survival in a multivariable analysis (hazard ratio, 1.29; P = .0009 for plasma; HR, 1.79; P = .0009 for urine; HR, 1.91; P = .0004 for combined) after adjusting for cancer type, age, sex, and stage IV or high-grade disease.

These findings showed an association of free GAGome alterations with aggressive cancer phenotypes and suggested that scores below the 95% specificity cutoff might have a better prognosis, the authors comment.

In addition, other analyses showed that free GAGomes predicted the putative cancer location with 89% accuracy. And finally, to confirm whether the free GAGome MCED scores could be used for screening, a validation analysis was conducted using a typical “screening population,” which requires at least 99% specificity. The combined free GAGomes were able to predict a poor prognosis of any cancer type within 18 months and with 43% sensitivity (21% in stage I; n = 121 and 49 cases).

Dr. Gatto believes that these results, as well as those from other studies looking at glycosaminoglycans as cancer biomarkers, will lead to the next steps of development. “But I speculate that this test could be most useful to assess in a cheap, practical, and noninvasive manner if a person at increased risk of cancer should be selected for cancer screening as part of established or emerging screening programs.”

The study was sponsored by Elypta. Dr. Gatto is listed as an inventor in patent applications related to the biomarkers described in this study and later assigned to Elypta, and is a shareholder and employed at Elypta. Dr. Hirsch reports no relevant financial relationships. Dr. Klein is a consultant for GRAIL and an investigator for CCGA and Pathfinder.

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

Much attention has been given recently to the idea of detecting many different types of cancer from a single blood test, and a new test claiming to do that has just been reported.

The leader in this field is the Galleri test (from GRAIL) which is already in clinical use in some health care networks across the United States. That test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA (cfDNA) in a blood sample.

The new test, under development by Swedish biotechnology company Elypta AB, has a different premise. It can detect 14 cancer types based on the analysis of glycosaminoglycans, which are a diverse group of polysaccharides that are altered by the presence of tumors. Using plasma and urine samples, the method had a 41.6%-62.3% sensitivity for detecting stage I cancer at 95% specificity.

In comparison, say the authors, other assays have reported 39%-73% sensitivity to stage I cancers, but these estimates are usually limited to 12 cancer types that are considered “high-signal,” and the assays perform poorly in cancers that emit little cfDNA, such as genitourinary and brain malignancies.

“The main advantage of glycosaminoglycans appears to be that they change in the blood and urine at the earliest stages of cancer,” said study author Francesco Gatto, PhD, founder and chief scientific officer at Elypta. “Consequently, this method showed an impressive detection rate in stage I compared to other emerging methods.”

The study was published online in Proceedings of the National Academy of Sciences.


 

Combine tests?

Dr. Gatto commented that he “could envision that one day we may be able to combine these methods.”

“The same blood specimen could be used to test both glycosaminoglycans and genomic biomarkers,” said Dr. Gatto. “This strategy could hopefully detect even more cancers than with either method alone, and the resulting performance may well be sufficient as a one-stop-shop screening program.”

So how does the new test from Elypta compare with the Galleri test?

“Galleri and similar methods mostly focused on information coming from molecules of DNA naturally floating in the blood,” explained Dr. Gatto. “It makes sense to conduct research there because cancers typically start with events in the DNA.”

He noted that the current study explored a new layer of information, molecules called glycosaminoglycans, that participate in the metabolism of cancer.

“This method detected many cancers that the previous methods missed, and a substantial proportion of these were at stage I,” said Dr. Gatto. “Cancer is a complex disease, so the most layers of information we can probe noninvasively, say with a blood test, the more likely we can catch more cancers at its earliest stage.”

Other platforms typically rely on sequencing and detecting cancer-derived fractions of cfDNA, but these methods have challenges that can interfere with their usage. For example, some cancer types do not shed sufficient cfDNA and it cannot be accurately measured.

“An advantage on focusing on glycosaminoglycans is that the method does not require next-generation sequencing or similarly complex assays because glycosaminoglycans are informative with less than 10 simultaneous measurements as opposed to Galleri that looks at over 1 million DNA methylation sites,” he said.

“This makes the assay behind the test much cheaper and robust – we estimated a 5-10 times lower cost difference,” Dr. Gatto said.
 

Prospective and comparative data needed

In a comment, Eric Klein, MD, emeritus chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic explained that the “only accurate way to know how a test will perform in an intended-use population is to actually test it in that population. It’s not possible to extrapolate results directly from a case-control study.”

Cancers shed many different biologic markers into body fluids, but which of these signals will be best to serve as the basis of an MCED (multi-cancer detection test) that has clinical utility in a screening population has yet to be determined, he noted. “And it’s possible that no single test will be optimum for every clinical situation.”

“The results of this study appear promising, but it is not possible to claim superiority of one test over another based on individual case-control studies because of uncontrolled differences in the selected populations,” Dr. Klein continued. “The only scientifically accurate way to do this is to perform different tests on the same patient samples in a head-to-head comparison.”

There is only one study that he is aware of that has done this recently, in which multiple different assays looking at various signals in cell-free DNA were directly compared on the same samples (Cancer cell. 2022;40:1537-49.e12). “A targeted methylation assay that is the basis for Galleri was best for the lowest limit of detection and for predicting cancer site of origin,” said Dr. Klein.

Another expert agreed that a direct head-to-head study is needed to compare assays. “Based on this data, you cannot say that this method is better than the other one because that requires a comparative study,” said Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology, Tisch Cancer Institute at Mount Sinai, New York.

Metabolomics is interesting, and the data are encouraging, he continued. “But this is a multicancer early detection test and metabolism changes may vary from cancer type to cancer type. I’m not sure that the metabolism of lung cancer is the same as that of a gynecologic cancer.”

Dr. Hirsch also pointed out that there could also be confounding factors. “They have excluded inflammatory disease, but there can be other variables such as smoking,” he said. “Overall it gives some interesting perspectives but I would like to see more prospective validation and studies in specific disease groups, and eventually comparative studies with other methodologies.”
 

Study details

The authors evaluated if plasma and urine free GAGomes (free glycosaminoglycan profiles) deviated from baseline physiological levels in 14 cancer types and could serve as metabolic cancer biomarkers. They also then validated using free GAGomes for MCED in an external population with 2,064 samples obtained from 1,260 patients with cancer and healthy individuals.

In an in vivo cancer progression model, they observed widespread cancer-specific changes in biofluidic free GAGomes and then developed three machine-learning models based on urine (n_urine = 220 cancer vs. 360 healthy) and plasma (n_plasma = 517 cancer vs. 425 healthy) free GAGomes that were able to detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 (with up to 62% sensitivity to stage I disease at 95% specificity).

To assess if altered GAGome features associated with cancer suggested more aggressive tumor biology, they correlated each score with overall survival. The median follow-up time was 17 months in the plasma cohort (n = 370 across 13 cancer types), 15 months in the urine cohort (n = 162 across 4 cancer types), and 15 months in the combined cohort (n = 152 across 4 cancer types).

They found that all three scores independently predicted overall survival in a multivariable analysis (hazard ratio, 1.29; P = .0009 for plasma; HR, 1.79; P = .0009 for urine; HR, 1.91; P = .0004 for combined) after adjusting for cancer type, age, sex, and stage IV or high-grade disease.

These findings showed an association of free GAGome alterations with aggressive cancer phenotypes and suggested that scores below the 95% specificity cutoff might have a better prognosis, the authors comment.

In addition, other analyses showed that free GAGomes predicted the putative cancer location with 89% accuracy. And finally, to confirm whether the free GAGome MCED scores could be used for screening, a validation analysis was conducted using a typical “screening population,” which requires at least 99% specificity. The combined free GAGomes were able to predict a poor prognosis of any cancer type within 18 months and with 43% sensitivity (21% in stage I; n = 121 and 49 cases).

Dr. Gatto believes that these results, as well as those from other studies looking at glycosaminoglycans as cancer biomarkers, will lead to the next steps of development. “But I speculate that this test could be most useful to assess in a cheap, practical, and noninvasive manner if a person at increased risk of cancer should be selected for cancer screening as part of established or emerging screening programs.”

The study was sponsored by Elypta. Dr. Gatto is listed as an inventor in patent applications related to the biomarkers described in this study and later assigned to Elypta, and is a shareholder and employed at Elypta. Dr. Hirsch reports no relevant financial relationships. Dr. Klein is a consultant for GRAIL and an investigator for CCGA and Pathfinder.

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

Much attention has been given recently to the idea of detecting many different types of cancer from a single blood test, and a new test claiming to do that has just been reported.

The leader in this field is the Galleri test (from GRAIL) which is already in clinical use in some health care networks across the United States. That test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA (cfDNA) in a blood sample.

The new test, under development by Swedish biotechnology company Elypta AB, has a different premise. It can detect 14 cancer types based on the analysis of glycosaminoglycans, which are a diverse group of polysaccharides that are altered by the presence of tumors. Using plasma and urine samples, the method had a 41.6%-62.3% sensitivity for detecting stage I cancer at 95% specificity.

In comparison, say the authors, other assays have reported 39%-73% sensitivity to stage I cancers, but these estimates are usually limited to 12 cancer types that are considered “high-signal,” and the assays perform poorly in cancers that emit little cfDNA, such as genitourinary and brain malignancies.

“The main advantage of glycosaminoglycans appears to be that they change in the blood and urine at the earliest stages of cancer,” said study author Francesco Gatto, PhD, founder and chief scientific officer at Elypta. “Consequently, this method showed an impressive detection rate in stage I compared to other emerging methods.”

The study was published online in Proceedings of the National Academy of Sciences.


 

Combine tests?

Dr. Gatto commented that he “could envision that one day we may be able to combine these methods.”

“The same blood specimen could be used to test both glycosaminoglycans and genomic biomarkers,” said Dr. Gatto. “This strategy could hopefully detect even more cancers than with either method alone, and the resulting performance may well be sufficient as a one-stop-shop screening program.”

So how does the new test from Elypta compare with the Galleri test?

“Galleri and similar methods mostly focused on information coming from molecules of DNA naturally floating in the blood,” explained Dr. Gatto. “It makes sense to conduct research there because cancers typically start with events in the DNA.”

He noted that the current study explored a new layer of information, molecules called glycosaminoglycans, that participate in the metabolism of cancer.

“This method detected many cancers that the previous methods missed, and a substantial proportion of these were at stage I,” said Dr. Gatto. “Cancer is a complex disease, so the most layers of information we can probe noninvasively, say with a blood test, the more likely we can catch more cancers at its earliest stage.”

Other platforms typically rely on sequencing and detecting cancer-derived fractions of cfDNA, but these methods have challenges that can interfere with their usage. For example, some cancer types do not shed sufficient cfDNA and it cannot be accurately measured.

“An advantage on focusing on glycosaminoglycans is that the method does not require next-generation sequencing or similarly complex assays because glycosaminoglycans are informative with less than 10 simultaneous measurements as opposed to Galleri that looks at over 1 million DNA methylation sites,” he said.

“This makes the assay behind the test much cheaper and robust – we estimated a 5-10 times lower cost difference,” Dr. Gatto said.
 

Prospective and comparative data needed

In a comment, Eric Klein, MD, emeritus chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic explained that the “only accurate way to know how a test will perform in an intended-use population is to actually test it in that population. It’s not possible to extrapolate results directly from a case-control study.”

Cancers shed many different biologic markers into body fluids, but which of these signals will be best to serve as the basis of an MCED (multi-cancer detection test) that has clinical utility in a screening population has yet to be determined, he noted. “And it’s possible that no single test will be optimum for every clinical situation.”

“The results of this study appear promising, but it is not possible to claim superiority of one test over another based on individual case-control studies because of uncontrolled differences in the selected populations,” Dr. Klein continued. “The only scientifically accurate way to do this is to perform different tests on the same patient samples in a head-to-head comparison.”

There is only one study that he is aware of that has done this recently, in which multiple different assays looking at various signals in cell-free DNA were directly compared on the same samples (Cancer cell. 2022;40:1537-49.e12). “A targeted methylation assay that is the basis for Galleri was best for the lowest limit of detection and for predicting cancer site of origin,” said Dr. Klein.

Another expert agreed that a direct head-to-head study is needed to compare assays. “Based on this data, you cannot say that this method is better than the other one because that requires a comparative study,” said Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology, Tisch Cancer Institute at Mount Sinai, New York.

Metabolomics is interesting, and the data are encouraging, he continued. “But this is a multicancer early detection test and metabolism changes may vary from cancer type to cancer type. I’m not sure that the metabolism of lung cancer is the same as that of a gynecologic cancer.”

Dr. Hirsch also pointed out that there could also be confounding factors. “They have excluded inflammatory disease, but there can be other variables such as smoking,” he said. “Overall it gives some interesting perspectives but I would like to see more prospective validation and studies in specific disease groups, and eventually comparative studies with other methodologies.”
 

Study details

The authors evaluated if plasma and urine free GAGomes (free glycosaminoglycan profiles) deviated from baseline physiological levels in 14 cancer types and could serve as metabolic cancer biomarkers. They also then validated using free GAGomes for MCED in an external population with 2,064 samples obtained from 1,260 patients with cancer and healthy individuals.

In an in vivo cancer progression model, they observed widespread cancer-specific changes in biofluidic free GAGomes and then developed three machine-learning models based on urine (n_urine = 220 cancer vs. 360 healthy) and plasma (n_plasma = 517 cancer vs. 425 healthy) free GAGomes that were able to detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 (with up to 62% sensitivity to stage I disease at 95% specificity).

To assess if altered GAGome features associated with cancer suggested more aggressive tumor biology, they correlated each score with overall survival. The median follow-up time was 17 months in the plasma cohort (n = 370 across 13 cancer types), 15 months in the urine cohort (n = 162 across 4 cancer types), and 15 months in the combined cohort (n = 152 across 4 cancer types).

They found that all three scores independently predicted overall survival in a multivariable analysis (hazard ratio, 1.29; P = .0009 for plasma; HR, 1.79; P = .0009 for urine; HR, 1.91; P = .0004 for combined) after adjusting for cancer type, age, sex, and stage IV or high-grade disease.

These findings showed an association of free GAGome alterations with aggressive cancer phenotypes and suggested that scores below the 95% specificity cutoff might have a better prognosis, the authors comment.

In addition, other analyses showed that free GAGomes predicted the putative cancer location with 89% accuracy. And finally, to confirm whether the free GAGome MCED scores could be used for screening, a validation analysis was conducted using a typical “screening population,” which requires at least 99% specificity. The combined free GAGomes were able to predict a poor prognosis of any cancer type within 18 months and with 43% sensitivity (21% in stage I; n = 121 and 49 cases).

Dr. Gatto believes that these results, as well as those from other studies looking at glycosaminoglycans as cancer biomarkers, will lead to the next steps of development. “But I speculate that this test could be most useful to assess in a cheap, practical, and noninvasive manner if a person at increased risk of cancer should be selected for cancer screening as part of established or emerging screening programs.”

The study was sponsored by Elypta. Dr. Gatto is listed as an inventor in patent applications related to the biomarkers described in this study and later assigned to Elypta, and is a shareholder and employed at Elypta. Dr. Hirsch reports no relevant financial relationships. Dr. Klein is a consultant for GRAIL and an investigator for CCGA and Pathfinder.

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

SAN ANTONIO – A wide range of research on hormone receptor (HR)–positive breast cancer was presented at the San Antonio Breast Cancer Symposium.

This news organization spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease – the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.
 

1. Addressing an unmet need

Data from the phase 3 CAPItello-291 clinical trial showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer, compared with those who received placebo plus fulvestrant (GS3-04).

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio, 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months vs. 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8% vs. 9.7% among the patients with AKT alterations.

Dr. Mouabbi noted that the study “met its primary endpoint” and that, importantly, it “addresses an area of unmet need.”

“The study’s treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer,” Dr. Mouabbi explained. He noted, “We’ve always wanted to tackle that pathway effectively, and it looks like this drug can do that.”
 

2. Next-generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen-receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months vs. 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg, compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

“In this trial, camizestrant looks like a more beneficial treatment in the target group,” said Dr. Kaklamani. “This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant.” In addition, “camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly.”
 

3. Pregnancy risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That’s what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

“This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer,” Dr. Kaklamani said. “It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study.”

Dr. Mouabbi agreed, noting, “Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients.”
 

4. Assay identifies OFS benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1,717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Dr. Kaklamani highlighted this study’s importance, saying, “Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity.”
 

5. Optimizing elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Dr. Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤ 1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS – the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

“What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months,” Dr. Kaklamani said. These data can help us determine who may do best on the drug, she added.

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

SAN ANTONIO – A wide range of research on hormone receptor (HR)–positive breast cancer was presented at the San Antonio Breast Cancer Symposium.

This news organization spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease – the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.
 

1. Addressing an unmet need

Data from the phase 3 CAPItello-291 clinical trial showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer, compared with those who received placebo plus fulvestrant (GS3-04).

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio, 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months vs. 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8% vs. 9.7% among the patients with AKT alterations.

Dr. Mouabbi noted that the study “met its primary endpoint” and that, importantly, it “addresses an area of unmet need.”

“The study’s treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer,” Dr. Mouabbi explained. He noted, “We’ve always wanted to tackle that pathway effectively, and it looks like this drug can do that.”
 

2. Next-generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen-receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months vs. 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg, compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

“In this trial, camizestrant looks like a more beneficial treatment in the target group,” said Dr. Kaklamani. “This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant.” In addition, “camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly.”
 

3. Pregnancy risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That’s what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

“This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer,” Dr. Kaklamani said. “It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study.”

Dr. Mouabbi agreed, noting, “Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients.”
 

4. Assay identifies OFS benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1,717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Dr. Kaklamani highlighted this study’s importance, saying, “Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity.”
 

5. Optimizing elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Dr. Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤ 1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS – the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

“What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months,” Dr. Kaklamani said. These data can help us determine who may do best on the drug, she added.

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

SAN ANTONIO – A wide range of research on hormone receptor (HR)–positive breast cancer was presented at the San Antonio Breast Cancer Symposium.

This news organization spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease – the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.
 

1. Addressing an unmet need

Data from the phase 3 CAPItello-291 clinical trial showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer, compared with those who received placebo plus fulvestrant (GS3-04).

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio, 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months vs. 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8% vs. 9.7% among the patients with AKT alterations.

Dr. Mouabbi noted that the study “met its primary endpoint” and that, importantly, it “addresses an area of unmet need.”

“The study’s treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer,” Dr. Mouabbi explained. He noted, “We’ve always wanted to tackle that pathway effectively, and it looks like this drug can do that.”
 

2. Next-generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen-receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months vs. 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg, compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

“In this trial, camizestrant looks like a more beneficial treatment in the target group,” said Dr. Kaklamani. “This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant.” In addition, “camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly.”
 

3. Pregnancy risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That’s what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

“This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer,” Dr. Kaklamani said. “It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study.”

Dr. Mouabbi agreed, noting, “Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients.”
 

4. Assay identifies OFS benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1,717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Dr. Kaklamani highlighted this study’s importance, saying, “Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity.”
 

5. Optimizing elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Dr. Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤ 1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS – the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

“What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months,” Dr. Kaklamani said. These data can help us determine who may do best on the drug, she added.

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

Meharry Medical College, one of the oldest and largest historically Black academic health institutions in the United States, disclosed recently that its MD program had been placed on probationary status after a national accrediting agency’s onsite survey uncovered “infrastructure” problems earlier this year. Those include faculty shortages and inadequate student access to financial aid as well as to career and wellness counseling.

The inspection was conducted by the Liaison Committee on Medical Education (LCME), an accrediting body sponsored by the Association of American Medical Colleges and the American Medical Association.

While participation is voluntary, institutions must comply with 12 standards to maintain their standing. These include hiring qualified faculty and providing students with financial aid and debt management counseling.

Jeannette South-Paul, MD, Meharry’s senior vice president and chief academic officer, said in an interview that the degree program remains fully accredited despite the fact that LCME representatives found “notable areas of concern,” including the “need for some infrastructure updates and additional educational and financial resources for students.”

Specifically, students did not have sufficient access to advising services, broadband internet, and study spaces. In addition, faculty shortages caused delays in student evaluations, she said.

The new status does not affect the ability of students to complete their medical degrees or residency programs, she said. Dr. South-Paul added that school officials have begun addressing several of the issues and anticipate a swift resolution “guided by an aggressive action plan over the next 18-24 months.”

The university, located in Nashville, Tenn., has had accreditation problems before. In January, following a site visit and low scores on annual resident surveys, the Accreditation Council for Graduate Medical Education (ACGME) placed several of the schools’ residency and fellowship programs on probationary status.

At the time, school officials said that all programs would remain accredited, and they committed to expanding available resources, such as hiring additional staff and an independent expert to make program recommendations. A follow-up site visit was scheduled for August.

Regarding the most recent accreditation challenges, Veronica M. Catanese, MD, MBA, co-secretary of LCME, said the organization could only disclose the accreditation status of a medical school.

“LCME is not able to discuss any details concerning the accreditation of individual medical education programs, including the review process, resulting decisions, or survey results,” she said.

Established medical education programs typically undergo a self-study process and a full survey visit every 8 years. According to LCME’s website, a full survey visit may be conducted sooner if concerns arise about the program’s quality or sustainability.

The LCME program directory lists Meharry Medical College’s accreditation status as “full, on probation.” The next survey visit is scheduled for the 2023-2024 school year.

LCME accreditation is a prerequisite for having access to federal grants and programs, such as Title VII funding, which helps increase minority participation in health care careers. In addition, most state licensure boards and ACGME-affiliated residency programs require applicants to graduate from an LCME-accredited school.

Last year, when Meharry Medical College received pandemic aid money as part of the CARES Act, the school distributed nearly $10 million in scholarships to students – many of whom come from modest-income families and struggle to afford college tuition.

But in general, endowments to historically Black colleges and universities (HBCUs) are often at least 70% smaller than those made to non-HBCUs, which raises the question: Does the lack of funding make it more difficult for schools such as Meharry to maintain accreditation standards?

“Many different factors played into this finding by LCME,” said Dr. South-Paul. “It is a well-known fact that HBCUs have historically not been as well funded or possess the same size endowments as their mainstream academic peers. That is true of Meharry, but it would not be accurate to say this probation is because we are an HBCU.”

Similarly, Dr. Catanese said there is no evidence that HBCUs and non-HBCUs differ in their ability to meet LCME accreditation standards.

About half of the school’s residency and fellowship programs continue to have accreditation problems. According to ACGME’s database, the internal medicine program is currently on “continued accreditation with warning” status. The psychiatry and ob.gyn. programs are on “probationary accreditation” after receiving warnings in previous years.

Meharry was chartered in 1915 but was founded in 1876 as one of the first medical schools in the South for Black Americans.

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

Meharry Medical College, one of the oldest and largest historically Black academic health institutions in the United States, disclosed recently that its MD program had been placed on probationary status after a national accrediting agency’s onsite survey uncovered “infrastructure” problems earlier this year. Those include faculty shortages and inadequate student access to financial aid as well as to career and wellness counseling.

The inspection was conducted by the Liaison Committee on Medical Education (LCME), an accrediting body sponsored by the Association of American Medical Colleges and the American Medical Association.

While participation is voluntary, institutions must comply with 12 standards to maintain their standing. These include hiring qualified faculty and providing students with financial aid and debt management counseling.

Jeannette South-Paul, MD, Meharry’s senior vice president and chief academic officer, said in an interview that the degree program remains fully accredited despite the fact that LCME representatives found “notable areas of concern,” including the “need for some infrastructure updates and additional educational and financial resources for students.”

Specifically, students did not have sufficient access to advising services, broadband internet, and study spaces. In addition, faculty shortages caused delays in student evaluations, she said.

The new status does not affect the ability of students to complete their medical degrees or residency programs, she said. Dr. South-Paul added that school officials have begun addressing several of the issues and anticipate a swift resolution “guided by an aggressive action plan over the next 18-24 months.”

The university, located in Nashville, Tenn., has had accreditation problems before. In January, following a site visit and low scores on annual resident surveys, the Accreditation Council for Graduate Medical Education (ACGME) placed several of the schools’ residency and fellowship programs on probationary status.

At the time, school officials said that all programs would remain accredited, and they committed to expanding available resources, such as hiring additional staff and an independent expert to make program recommendations. A follow-up site visit was scheduled for August.

Regarding the most recent accreditation challenges, Veronica M. Catanese, MD, MBA, co-secretary of LCME, said the organization could only disclose the accreditation status of a medical school.

“LCME is not able to discuss any details concerning the accreditation of individual medical education programs, including the review process, resulting decisions, or survey results,” she said.

Established medical education programs typically undergo a self-study process and a full survey visit every 8 years. According to LCME’s website, a full survey visit may be conducted sooner if concerns arise about the program’s quality or sustainability.

The LCME program directory lists Meharry Medical College’s accreditation status as “full, on probation.” The next survey visit is scheduled for the 2023-2024 school year.

LCME accreditation is a prerequisite for having access to federal grants and programs, such as Title VII funding, which helps increase minority participation in health care careers. In addition, most state licensure boards and ACGME-affiliated residency programs require applicants to graduate from an LCME-accredited school.

Last year, when Meharry Medical College received pandemic aid money as part of the CARES Act, the school distributed nearly $10 million in scholarships to students – many of whom come from modest-income families and struggle to afford college tuition.

But in general, endowments to historically Black colleges and universities (HBCUs) are often at least 70% smaller than those made to non-HBCUs, which raises the question: Does the lack of funding make it more difficult for schools such as Meharry to maintain accreditation standards?

“Many different factors played into this finding by LCME,” said Dr. South-Paul. “It is a well-known fact that HBCUs have historically not been as well funded or possess the same size endowments as their mainstream academic peers. That is true of Meharry, but it would not be accurate to say this probation is because we are an HBCU.”

Similarly, Dr. Catanese said there is no evidence that HBCUs and non-HBCUs differ in their ability to meet LCME accreditation standards.

About half of the school’s residency and fellowship programs continue to have accreditation problems. According to ACGME’s database, the internal medicine program is currently on “continued accreditation with warning” status. The psychiatry and ob.gyn. programs are on “probationary accreditation” after receiving warnings in previous years.

Meharry was chartered in 1915 but was founded in 1876 as one of the first medical schools in the South for Black Americans.

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

Meharry Medical College, one of the oldest and largest historically Black academic health institutions in the United States, disclosed recently that its MD program had been placed on probationary status after a national accrediting agency’s onsite survey uncovered “infrastructure” problems earlier this year. Those include faculty shortages and inadequate student access to financial aid as well as to career and wellness counseling.

The inspection was conducted by the Liaison Committee on Medical Education (LCME), an accrediting body sponsored by the Association of American Medical Colleges and the American Medical Association.

While participation is voluntary, institutions must comply with 12 standards to maintain their standing. These include hiring qualified faculty and providing students with financial aid and debt management counseling.

Jeannette South-Paul, MD, Meharry’s senior vice president and chief academic officer, said in an interview that the degree program remains fully accredited despite the fact that LCME representatives found “notable areas of concern,” including the “need for some infrastructure updates and additional educational and financial resources for students.”

Specifically, students did not have sufficient access to advising services, broadband internet, and study spaces. In addition, faculty shortages caused delays in student evaluations, she said.

The new status does not affect the ability of students to complete their medical degrees or residency programs, she said. Dr. South-Paul added that school officials have begun addressing several of the issues and anticipate a swift resolution “guided by an aggressive action plan over the next 18-24 months.”

The university, located in Nashville, Tenn., has had accreditation problems before. In January, following a site visit and low scores on annual resident surveys, the Accreditation Council for Graduate Medical Education (ACGME) placed several of the schools’ residency and fellowship programs on probationary status.

At the time, school officials said that all programs would remain accredited, and they committed to expanding available resources, such as hiring additional staff and an independent expert to make program recommendations. A follow-up site visit was scheduled for August.

Regarding the most recent accreditation challenges, Veronica M. Catanese, MD, MBA, co-secretary of LCME, said the organization could only disclose the accreditation status of a medical school.

“LCME is not able to discuss any details concerning the accreditation of individual medical education programs, including the review process, resulting decisions, or survey results,” she said.

Established medical education programs typically undergo a self-study process and a full survey visit every 8 years. According to LCME’s website, a full survey visit may be conducted sooner if concerns arise about the program’s quality or sustainability.

The LCME program directory lists Meharry Medical College’s accreditation status as “full, on probation.” The next survey visit is scheduled for the 2023-2024 school year.

LCME accreditation is a prerequisite for having access to federal grants and programs, such as Title VII funding, which helps increase minority participation in health care careers. In addition, most state licensure boards and ACGME-affiliated residency programs require applicants to graduate from an LCME-accredited school.

Last year, when Meharry Medical College received pandemic aid money as part of the CARES Act, the school distributed nearly $10 million in scholarships to students – many of whom come from modest-income families and struggle to afford college tuition.

But in general, endowments to historically Black colleges and universities (HBCUs) are often at least 70% smaller than those made to non-HBCUs, which raises the question: Does the lack of funding make it more difficult for schools such as Meharry to maintain accreditation standards?

“Many different factors played into this finding by LCME,” said Dr. South-Paul. “It is a well-known fact that HBCUs have historically not been as well funded or possess the same size endowments as their mainstream academic peers. That is true of Meharry, but it would not be accurate to say this probation is because we are an HBCU.”

Similarly, Dr. Catanese said there is no evidence that HBCUs and non-HBCUs differ in their ability to meet LCME accreditation standards.

About half of the school’s residency and fellowship programs continue to have accreditation problems. According to ACGME’s database, the internal medicine program is currently on “continued accreditation with warning” status. The psychiatry and ob.gyn. programs are on “probationary accreditation” after receiving warnings in previous years.

Meharry was chartered in 1915 but was founded in 1876 as one of the first medical schools in the South for Black Americans.

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

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.

“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”

The Diuretic Comparison Project (DCP) trial, showing no difference in reduction of clinical events between the thiazide diuretics chlorthalidone and hydrochlorothiazide when used for the treatment of hypertension, has now been published. 

The trial was first presented at the 2022 annual scientific sessions of the American Heart Association. 

Courtesy April Eilers

In the current paper, published online in the New England Journal of Medicine, the authors, led by Areef Ishani, MD, Minneapolis Veterans Affairs Health Care System, explained that early studies suggested that chlorthalidone was superior to hydrochlorothiazide in patients with hypertension, but more recent observational studies have shown that the two drugs reduced cardiovascular events at a similar rate. Chlorthalidone may be associated with an increased risk of adverse events, including hypokalemia.

They noted that, in 2020, Part D Medicare expenditures showed that approximately 1.5 million persons received prescriptions for chlorthalidone, compared with 11.5 million who received prescriptions for hydrochlorothiazide, despite guidelines that recommended chlorthalidone as the preferred agent. The discrepancy between guideline recommendation and real-world use is possibly related to the belief that chlorthalidone has a greater risk for adverse effects without clear evidence for differences in cardiovascular outcomes, the authors suggested.

They conducted the current study to directly compare the effect of the two agents on cardiovascular outcomes in patients with hypertension.

The pragmatic DCP trial was carried out within the VA Healthcare System, and randomly assigned 13,523 patients (mean age, 72.5 years) with hypertension who were receiving hydrochlorothiazide at baseline (25 or 50 mg per day) to continue hydrochlorothiazide at their baseline dose or to switch to chlorthalidone (12.5 or 25 mg per day).

The mean baseline systolic blood pressure was 139 mm Hg in both trial groups and did not change substantially during the trial.

Over a median follow-up of 2.4 years, there was no difference in the primary outcome – a composite of MI, stroke, hospitalization for heart failure, urgent coronary revascularization for unstable angina, and non–cancer-related death – between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%), giving a hazard ratio of 1.04 (95% CI, 0.94-1.16; P = .45).

In addition, there were no treatment differences between the two groups in any primary outcome component. Hypokalemia and potassium supplement use were more common in the chlorthalidone group than in the hydrochlorothiazide group.

‘Importance lies in the design’

In an accompanying editorial, Julie R. Ingelfinger, MD, deputy editor of the New England Journal of Medicine, said the results are not surprising and may not change clinical practice. But she suggested that the importance of the trial lies in its design, which shows that a high-quality pragmatic comparative effectiveness trial can be accomplished in a cost-effective manner within a health care system with little disruption in patient care.

Dr. Ingelfinger pointed out several limitations of the trial. These include a lower-than-expected occurrence of primary outcome events, and the stipulation that patients were eligible to participate only if they continued to have hypertension while receiving hydrochlorothiazide.

In addition, 95% of the participants were receiving 25 mg of hydrochlorothiazide and only 5% were receiving 50 mg, which limited comparisons of the dose generally used in practice. Also, only approximately 13% of the patients were receiving hydrochlorothiazide alone for the treatment of hypertension at baseline.

She noted that the DCP is the first head-to-head comparison of hydrochlorothiazide and chlorthalidone in a randomized, prospective outcome trial.

“Without an apparent difference in the hazard ratios for the primary outcome in the two groups over the median follow-up of 2.4 years, results suggest that chlorthalidone therapy remains a good choice for hypertension despite the secondary observation that hypokalemia was more common with chlorthalidone than with hydrochlorothiazide,” Dr. Ingelfinger said.

“Although a subgroup analysis suggested that chlorthalidone was better than hydrochlorothiazide for participants with a history of myocardial infarction or stroke, that result may have been by chance,” she added.

As clinicians generally prefer using hydrochlorothiazide, she suggested that these DCP results will not provide any impetus for change.

“Furthermore, combined therapy and polypills may alter therapy beyond the results of this well-done, highly anticipated trial. Thus, its major effect may be as a model for other pragmatic study programs, which are greatly needed,” she concluded.

This study was supported by the Veterans Affairs Cooperative Studies Program through a grant to the Diuretic Comparison Project. Dr. Ishani reported no relevant financial relationships. Dr. Ingelfinger reported book royalties from Springer and from St. Martin’s Press, outside the submitted work, and that she is employed by the New England Journal of Medicine as deputy editor.

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

The Diuretic Comparison Project (DCP) trial, showing no difference in reduction of clinical events between the thiazide diuretics chlorthalidone and hydrochlorothiazide when used for the treatment of hypertension, has now been published. 

The trial was first presented at the 2022 annual scientific sessions of the American Heart Association. 

Courtesy April Eilers

In the current paper, published online in the New England Journal of Medicine, the authors, led by Areef Ishani, MD, Minneapolis Veterans Affairs Health Care System, explained that early studies suggested that chlorthalidone was superior to hydrochlorothiazide in patients with hypertension, but more recent observational studies have shown that the two drugs reduced cardiovascular events at a similar rate. Chlorthalidone may be associated with an increased risk of adverse events, including hypokalemia.

They noted that, in 2020, Part D Medicare expenditures showed that approximately 1.5 million persons received prescriptions for chlorthalidone, compared with 11.5 million who received prescriptions for hydrochlorothiazide, despite guidelines that recommended chlorthalidone as the preferred agent. The discrepancy between guideline recommendation and real-world use is possibly related to the belief that chlorthalidone has a greater risk for adverse effects without clear evidence for differences in cardiovascular outcomes, the authors suggested.

They conducted the current study to directly compare the effect of the two agents on cardiovascular outcomes in patients with hypertension.

The pragmatic DCP trial was carried out within the VA Healthcare System, and randomly assigned 13,523 patients (mean age, 72.5 years) with hypertension who were receiving hydrochlorothiazide at baseline (25 or 50 mg per day) to continue hydrochlorothiazide at their baseline dose or to switch to chlorthalidone (12.5 or 25 mg per day).

The mean baseline systolic blood pressure was 139 mm Hg in both trial groups and did not change substantially during the trial.

Over a median follow-up of 2.4 years, there was no difference in the primary outcome – a composite of MI, stroke, hospitalization for heart failure, urgent coronary revascularization for unstable angina, and non–cancer-related death – between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%), giving a hazard ratio of 1.04 (95% CI, 0.94-1.16; P = .45).

In addition, there were no treatment differences between the two groups in any primary outcome component. Hypokalemia and potassium supplement use were more common in the chlorthalidone group than in the hydrochlorothiazide group.

‘Importance lies in the design’

In an accompanying editorial, Julie R. Ingelfinger, MD, deputy editor of the New England Journal of Medicine, said the results are not surprising and may not change clinical practice. But she suggested that the importance of the trial lies in its design, which shows that a high-quality pragmatic comparative effectiveness trial can be accomplished in a cost-effective manner within a health care system with little disruption in patient care.

Dr. Ingelfinger pointed out several limitations of the trial. These include a lower-than-expected occurrence of primary outcome events, and the stipulation that patients were eligible to participate only if they continued to have hypertension while receiving hydrochlorothiazide.

In addition, 95% of the participants were receiving 25 mg of hydrochlorothiazide and only 5% were receiving 50 mg, which limited comparisons of the dose generally used in practice. Also, only approximately 13% of the patients were receiving hydrochlorothiazide alone for the treatment of hypertension at baseline.

She noted that the DCP is the first head-to-head comparison of hydrochlorothiazide and chlorthalidone in a randomized, prospective outcome trial.

“Without an apparent difference in the hazard ratios for the primary outcome in the two groups over the median follow-up of 2.4 years, results suggest that chlorthalidone therapy remains a good choice for hypertension despite the secondary observation that hypokalemia was more common with chlorthalidone than with hydrochlorothiazide,” Dr. Ingelfinger said.

“Although a subgroup analysis suggested that chlorthalidone was better than hydrochlorothiazide for participants with a history of myocardial infarction or stroke, that result may have been by chance,” she added.

As clinicians generally prefer using hydrochlorothiazide, she suggested that these DCP results will not provide any impetus for change.

“Furthermore, combined therapy and polypills may alter therapy beyond the results of this well-done, highly anticipated trial. Thus, its major effect may be as a model for other pragmatic study programs, which are greatly needed,” she concluded.

This study was supported by the Veterans Affairs Cooperative Studies Program through a grant to the Diuretic Comparison Project. Dr. Ishani reported no relevant financial relationships. Dr. Ingelfinger reported book royalties from Springer and from St. Martin’s Press, outside the submitted work, and that she is employed by the New England Journal of Medicine as deputy editor.

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

The Diuretic Comparison Project (DCP) trial, showing no difference in reduction of clinical events between the thiazide diuretics chlorthalidone and hydrochlorothiazide when used for the treatment of hypertension, has now been published. 

The trial was first presented at the 2022 annual scientific sessions of the American Heart Association. 

Courtesy April Eilers

In the current paper, published online in the New England Journal of Medicine, the authors, led by Areef Ishani, MD, Minneapolis Veterans Affairs Health Care System, explained that early studies suggested that chlorthalidone was superior to hydrochlorothiazide in patients with hypertension, but more recent observational studies have shown that the two drugs reduced cardiovascular events at a similar rate. Chlorthalidone may be associated with an increased risk of adverse events, including hypokalemia.

They noted that, in 2020, Part D Medicare expenditures showed that approximately 1.5 million persons received prescriptions for chlorthalidone, compared with 11.5 million who received prescriptions for hydrochlorothiazide, despite guidelines that recommended chlorthalidone as the preferred agent. The discrepancy between guideline recommendation and real-world use is possibly related to the belief that chlorthalidone has a greater risk for adverse effects without clear evidence for differences in cardiovascular outcomes, the authors suggested.

They conducted the current study to directly compare the effect of the two agents on cardiovascular outcomes in patients with hypertension.

The pragmatic DCP trial was carried out within the VA Healthcare System, and randomly assigned 13,523 patients (mean age, 72.5 years) with hypertension who were receiving hydrochlorothiazide at baseline (25 or 50 mg per day) to continue hydrochlorothiazide at their baseline dose or to switch to chlorthalidone (12.5 or 25 mg per day).

The mean baseline systolic blood pressure was 139 mm Hg in both trial groups and did not change substantially during the trial.

Over a median follow-up of 2.4 years, there was no difference in the primary outcome – a composite of MI, stroke, hospitalization for heart failure, urgent coronary revascularization for unstable angina, and non–cancer-related death – between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%), giving a hazard ratio of 1.04 (95% CI, 0.94-1.16; P = .45).

In addition, there were no treatment differences between the two groups in any primary outcome component. Hypokalemia and potassium supplement use were more common in the chlorthalidone group than in the hydrochlorothiazide group.

‘Importance lies in the design’

In an accompanying editorial, Julie R. Ingelfinger, MD, deputy editor of the New England Journal of Medicine, said the results are not surprising and may not change clinical practice. But she suggested that the importance of the trial lies in its design, which shows that a high-quality pragmatic comparative effectiveness trial can be accomplished in a cost-effective manner within a health care system with little disruption in patient care.

Dr. Ingelfinger pointed out several limitations of the trial. These include a lower-than-expected occurrence of primary outcome events, and the stipulation that patients were eligible to participate only if they continued to have hypertension while receiving hydrochlorothiazide.

In addition, 95% of the participants were receiving 25 mg of hydrochlorothiazide and only 5% were receiving 50 mg, which limited comparisons of the dose generally used in practice. Also, only approximately 13% of the patients were receiving hydrochlorothiazide alone for the treatment of hypertension at baseline.

She noted that the DCP is the first head-to-head comparison of hydrochlorothiazide and chlorthalidone in a randomized, prospective outcome trial.

“Without an apparent difference in the hazard ratios for the primary outcome in the two groups over the median follow-up of 2.4 years, results suggest that chlorthalidone therapy remains a good choice for hypertension despite the secondary observation that hypokalemia was more common with chlorthalidone than with hydrochlorothiazide,” Dr. Ingelfinger said.

“Although a subgroup analysis suggested that chlorthalidone was better than hydrochlorothiazide for participants with a history of myocardial infarction or stroke, that result may have been by chance,” she added.

As clinicians generally prefer using hydrochlorothiazide, she suggested that these DCP results will not provide any impetus for change.

“Furthermore, combined therapy and polypills may alter therapy beyond the results of this well-done, highly anticipated trial. Thus, its major effect may be as a model for other pragmatic study programs, which are greatly needed,” she concluded.

This study was supported by the Veterans Affairs Cooperative Studies Program through a grant to the Diuretic Comparison Project. Dr. Ishani reported no relevant financial relationships. Dr. Ingelfinger reported book royalties from Springer and from St. Martin’s Press, outside the submitted work, and that she is employed by the New England Journal of Medicine as deputy editor.

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

Just 56% of infectious disease fellowship programs filled their 2023 slots, according to new data released by the National Resident Matching Program. Infectious disease (ID) fellowships had seen a jump in applications in the previous 2 years, but these new numbers may suggest a backward slide in a specialty that for many years has struggled to recruit residents.

This latest match rate in ID fellowships is lower than those of the previous 5 years. There are unfilled positions across the country, including in health care hot spots. In Boston, all three slots at Boston Medical Center ID fellowship program are currently empty.

“For our program, going unfilled is a pretty rare event,” said Daniel Bourque, MD, an assistant professor of infectious disease at Boston University and director of the program. “For a program in the city of Boston that’s at a large tertiary care center, that definitely was a big surprise.”

Many other ID fellowships have joined BMC in posting about their vacancies on social media, looking for residents who may not have matched in other fellowships and for physicians who initially decided not to pursue additional training but are now reconsidering.

“If you are interested in a career in this exciting field, in the amazing city of Seattle, with incredible and friendly colleagues, please contact us,” the University of Washington’s ID fellowship program tweeted. Tulane University, Creighton University, the University of Connecticut, Washington University in St. Louis, and the University of Colorado also advertised their unfilled positions.

Other ID doctors commiserated with the disappointing match year. “I made a new riddle after yesterday’s match results: In the hospital, everyone needs me. Yet, no one wants to be me. What am I? An ID doctor,” tweeted Nathan Nolan, MD, MPH, an infectious disease specialist at the Veterans Health Administration in St. Louis.
 

Infectious disease positions continue to grow

One contributor to this downturn could be the growing number of infectious disease programs offered, whereas the number of applicants has generally remained stable. In 2018, there were 394 slots at 151 infectious disease fellowship programs offered. For the 2023 match year, there were 441 slots at 175 programs.

At the same time, there has not been a notable rise in applicants. From match years 2018 to 2020, about 320 applicants applied for ID fellowship positions each year. There was a rise in in interest in first 2 years of the pandemic, with 404 and 387 applicants in the 2021 and 2022 match years, respectively. The most recent round suggests a return to prepandemic numbers, with 330 residents applying to ID programs.

“I think it’s fair to question whether, as a field, we should be increasing training programs and spots at this point, and if it’s better to focus on ways to increase interest and demand,” said Daniel Diekema, MD, an ID physician at Maine Medical Center in Portland. “Otherwise, we’re just going to look worse and worse every year,” he added, and the work that goes into creating these training opportunities will not have a return on investment.
 

More training, less pay

The fellowship recruitment issues combined with an already short supply of infectious disease specialists can be traced back to comparatively worse pay compared with other subspecialties, experts say. Infectious disease was the fifth lowest paid specialty in the 2022 Medscape Physician Compensation Report – ranking above only primary care specialties and diabetes and endocrinology.

Pursuing this subspeciality in medicine may not translate to higher pay, Dr. Diekema noted. For example, a physician who completes an internal medicine residency and then a 2- to 3-year infectious disease fellowship can make less than a physician who pursues hospital medicine directly after completing the same residency.

“You’re in a situation where you’re doing additional training to reduce your income earning potential, and that’s a very hard sales pitch to make,” he said. It’s become more difficult as student loan debts continue to increase, he added.

Because infectious disease is a cognitive specialty and does not perform procedures, it is at a disadvantage in a typical fee-for-service pay model. ID physicians also advise on hospital policies for testing and personal protective equipment, which is not always compensated, said Wendy Armstrong, MD, a professor of infectious diseases at Emory University, Atlanta.
 

A reflection of pandemic burnout?

Experts also wonder if the past 2 years of the pandemic and the notable burnout in ID and other in-demand specialties may have dissuaded applicants from pursuing the ID career path.

“This residency class is the class that started their training in June or July of 2020 and represent that residency class that has trained throughout the pandemic,” Dr. Bourque said. “Does [this low match rate] reflect a negative outlook on the field of ID because of COVID? Is it a reflection of trainee burnout in the setting of the pandemic?”

Dr. Diekema wonders if increased public scrutiny and politicization of the field may have discouraged residents. “The vilification of public health and [of] infectious disease experts like Dr. Fauci by significant portions of our society can be demoralizing,” he said. “People might say, ‘Why would I want to put myself through that?’ ”

But Dr. Armstrong doubts this is the case. “I’ve never had a resident tell me that was on their radar screen,” she said, noting that while there had been recent improvements in applicants, lower match numbers for ID fellowships have been a long-standing issue.
 

Rethinking reimbursement

Experts agree that pay issues need to be addressed to make ID a more attractive specialty. Moving away from traditional payment plans to value-based models using quality measurements specific to infectious disease could be one way to quantify the value of ID specialists in care systems.

The Infectious Diseases Society of America recently met with the panel that sets compensation rates for Medicare to discuss ways to increase compensation for ID, said IDSA president Carlos del Rio, MD. He is also a professor of medicine at Emory University.

ID specialists need to be able to put a dollar value to their policy work that’s not related to patient reimbursement, Dr. del Rio said. IDSA’s ongoing compensation initiative advocates for value-based care and provides salary negotiation tools for ID specialists, he added.

“Salaries shouldn’t simply be defined by what reimbursement is, and that’s true for other specialties,” such as hospital medicine and palliative care at many institutions, Dr. Armstrong said. “Infectious disease needs to be held at the same level of respect and value.”

But despite issues within the specialties, ID physicians remain passionate about their field.

“It is the most fascinating specialty I can ever imagine,” Dr. Armstrong said. Dr. Bourque agreed, noting the dynamic nature of specialty, with the emergence of new diseases like COVID-19 and reemergence of diseases like mpox (formerly called monkeypox), Zika, Ebola, and chikungunya in the past decade.

“There’s nothing about the field of infectious diseases that, in my mind, isn’t fascinating or rewarding enough to bring people in,” added Dr. Diekema. “The factors that are keeping people out are primarily economic factors and aspects of our health care system that need attention.”

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

Just 56% of infectious disease fellowship programs filled their 2023 slots, according to new data released by the National Resident Matching Program. Infectious disease (ID) fellowships had seen a jump in applications in the previous 2 years, but these new numbers may suggest a backward slide in a specialty that for many years has struggled to recruit residents.

This latest match rate in ID fellowships is lower than those of the previous 5 years. There are unfilled positions across the country, including in health care hot spots. In Boston, all three slots at Boston Medical Center ID fellowship program are currently empty.

“For our program, going unfilled is a pretty rare event,” said Daniel Bourque, MD, an assistant professor of infectious disease at Boston University and director of the program. “For a program in the city of Boston that’s at a large tertiary care center, that definitely was a big surprise.”

Many other ID fellowships have joined BMC in posting about their vacancies on social media, looking for residents who may not have matched in other fellowships and for physicians who initially decided not to pursue additional training but are now reconsidering.

“If you are interested in a career in this exciting field, in the amazing city of Seattle, with incredible and friendly colleagues, please contact us,” the University of Washington’s ID fellowship program tweeted. Tulane University, Creighton University, the University of Connecticut, Washington University in St. Louis, and the University of Colorado also advertised their unfilled positions.

Other ID doctors commiserated with the disappointing match year. “I made a new riddle after yesterday’s match results: In the hospital, everyone needs me. Yet, no one wants to be me. What am I? An ID doctor,” tweeted Nathan Nolan, MD, MPH, an infectious disease specialist at the Veterans Health Administration in St. Louis.
 

Infectious disease positions continue to grow

One contributor to this downturn could be the growing number of infectious disease programs offered, whereas the number of applicants has generally remained stable. In 2018, there were 394 slots at 151 infectious disease fellowship programs offered. For the 2023 match year, there were 441 slots at 175 programs.

At the same time, there has not been a notable rise in applicants. From match years 2018 to 2020, about 320 applicants applied for ID fellowship positions each year. There was a rise in in interest in first 2 years of the pandemic, with 404 and 387 applicants in the 2021 and 2022 match years, respectively. The most recent round suggests a return to prepandemic numbers, with 330 residents applying to ID programs.

“I think it’s fair to question whether, as a field, we should be increasing training programs and spots at this point, and if it’s better to focus on ways to increase interest and demand,” said Daniel Diekema, MD, an ID physician at Maine Medical Center in Portland. “Otherwise, we’re just going to look worse and worse every year,” he added, and the work that goes into creating these training opportunities will not have a return on investment.
 

More training, less pay

The fellowship recruitment issues combined with an already short supply of infectious disease specialists can be traced back to comparatively worse pay compared with other subspecialties, experts say. Infectious disease was the fifth lowest paid specialty in the 2022 Medscape Physician Compensation Report – ranking above only primary care specialties and diabetes and endocrinology.

Pursuing this subspeciality in medicine may not translate to higher pay, Dr. Diekema noted. For example, a physician who completes an internal medicine residency and then a 2- to 3-year infectious disease fellowship can make less than a physician who pursues hospital medicine directly after completing the same residency.

“You’re in a situation where you’re doing additional training to reduce your income earning potential, and that’s a very hard sales pitch to make,” he said. It’s become more difficult as student loan debts continue to increase, he added.

Because infectious disease is a cognitive specialty and does not perform procedures, it is at a disadvantage in a typical fee-for-service pay model. ID physicians also advise on hospital policies for testing and personal protective equipment, which is not always compensated, said Wendy Armstrong, MD, a professor of infectious diseases at Emory University, Atlanta.
 

A reflection of pandemic burnout?

Experts also wonder if the past 2 years of the pandemic and the notable burnout in ID and other in-demand specialties may have dissuaded applicants from pursuing the ID career path.

“This residency class is the class that started their training in June or July of 2020 and represent that residency class that has trained throughout the pandemic,” Dr. Bourque said. “Does [this low match rate] reflect a negative outlook on the field of ID because of COVID? Is it a reflection of trainee burnout in the setting of the pandemic?”

Dr. Diekema wonders if increased public scrutiny and politicization of the field may have discouraged residents. “The vilification of public health and [of] infectious disease experts like Dr. Fauci by significant portions of our society can be demoralizing,” he said. “People might say, ‘Why would I want to put myself through that?’ ”

But Dr. Armstrong doubts this is the case. “I’ve never had a resident tell me that was on their radar screen,” she said, noting that while there had been recent improvements in applicants, lower match numbers for ID fellowships have been a long-standing issue.
 

Rethinking reimbursement

Experts agree that pay issues need to be addressed to make ID a more attractive specialty. Moving away from traditional payment plans to value-based models using quality measurements specific to infectious disease could be one way to quantify the value of ID specialists in care systems.

The Infectious Diseases Society of America recently met with the panel that sets compensation rates for Medicare to discuss ways to increase compensation for ID, said IDSA president Carlos del Rio, MD. He is also a professor of medicine at Emory University.

ID specialists need to be able to put a dollar value to their policy work that’s not related to patient reimbursement, Dr. del Rio said. IDSA’s ongoing compensation initiative advocates for value-based care and provides salary negotiation tools for ID specialists, he added.

“Salaries shouldn’t simply be defined by what reimbursement is, and that’s true for other specialties,” such as hospital medicine and palliative care at many institutions, Dr. Armstrong said. “Infectious disease needs to be held at the same level of respect and value.”

But despite issues within the specialties, ID physicians remain passionate about their field.

“It is the most fascinating specialty I can ever imagine,” Dr. Armstrong said. Dr. Bourque agreed, noting the dynamic nature of specialty, with the emergence of new diseases like COVID-19 and reemergence of diseases like mpox (formerly called monkeypox), Zika, Ebola, and chikungunya in the past decade.

“There’s nothing about the field of infectious diseases that, in my mind, isn’t fascinating or rewarding enough to bring people in,” added Dr. Diekema. “The factors that are keeping people out are primarily economic factors and aspects of our health care system that need attention.”

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

Just 56% of infectious disease fellowship programs filled their 2023 slots, according to new data released by the National Resident Matching Program. Infectious disease (ID) fellowships had seen a jump in applications in the previous 2 years, but these new numbers may suggest a backward slide in a specialty that for many years has struggled to recruit residents.

This latest match rate in ID fellowships is lower than those of the previous 5 years. There are unfilled positions across the country, including in health care hot spots. In Boston, all three slots at Boston Medical Center ID fellowship program are currently empty.

“For our program, going unfilled is a pretty rare event,” said Daniel Bourque, MD, an assistant professor of infectious disease at Boston University and director of the program. “For a program in the city of Boston that’s at a large tertiary care center, that definitely was a big surprise.”

Many other ID fellowships have joined BMC in posting about their vacancies on social media, looking for residents who may not have matched in other fellowships and for physicians who initially decided not to pursue additional training but are now reconsidering.

“If you are interested in a career in this exciting field, in the amazing city of Seattle, with incredible and friendly colleagues, please contact us,” the University of Washington’s ID fellowship program tweeted. Tulane University, Creighton University, the University of Connecticut, Washington University in St. Louis, and the University of Colorado also advertised their unfilled positions.

Other ID doctors commiserated with the disappointing match year. “I made a new riddle after yesterday’s match results: In the hospital, everyone needs me. Yet, no one wants to be me. What am I? An ID doctor,” tweeted Nathan Nolan, MD, MPH, an infectious disease specialist at the Veterans Health Administration in St. Louis.
 

Infectious disease positions continue to grow

One contributor to this downturn could be the growing number of infectious disease programs offered, whereas the number of applicants has generally remained stable. In 2018, there were 394 slots at 151 infectious disease fellowship programs offered. For the 2023 match year, there were 441 slots at 175 programs.

At the same time, there has not been a notable rise in applicants. From match years 2018 to 2020, about 320 applicants applied for ID fellowship positions each year. There was a rise in in interest in first 2 years of the pandemic, with 404 and 387 applicants in the 2021 and 2022 match years, respectively. The most recent round suggests a return to prepandemic numbers, with 330 residents applying to ID programs.

“I think it’s fair to question whether, as a field, we should be increasing training programs and spots at this point, and if it’s better to focus on ways to increase interest and demand,” said Daniel Diekema, MD, an ID physician at Maine Medical Center in Portland. “Otherwise, we’re just going to look worse and worse every year,” he added, and the work that goes into creating these training opportunities will not have a return on investment.
 

More training, less pay

The fellowship recruitment issues combined with an already short supply of infectious disease specialists can be traced back to comparatively worse pay compared with other subspecialties, experts say. Infectious disease was the fifth lowest paid specialty in the 2022 Medscape Physician Compensation Report – ranking above only primary care specialties and diabetes and endocrinology.

Pursuing this subspeciality in medicine may not translate to higher pay, Dr. Diekema noted. For example, a physician who completes an internal medicine residency and then a 2- to 3-year infectious disease fellowship can make less than a physician who pursues hospital medicine directly after completing the same residency.

“You’re in a situation where you’re doing additional training to reduce your income earning potential, and that’s a very hard sales pitch to make,” he said. It’s become more difficult as student loan debts continue to increase, he added.

Because infectious disease is a cognitive specialty and does not perform procedures, it is at a disadvantage in a typical fee-for-service pay model. ID physicians also advise on hospital policies for testing and personal protective equipment, which is not always compensated, said Wendy Armstrong, MD, a professor of infectious diseases at Emory University, Atlanta.
 

A reflection of pandemic burnout?

Experts also wonder if the past 2 years of the pandemic and the notable burnout in ID and other in-demand specialties may have dissuaded applicants from pursuing the ID career path.

“This residency class is the class that started their training in June or July of 2020 and represent that residency class that has trained throughout the pandemic,” Dr. Bourque said. “Does [this low match rate] reflect a negative outlook on the field of ID because of COVID? Is it a reflection of trainee burnout in the setting of the pandemic?”

Dr. Diekema wonders if increased public scrutiny and politicization of the field may have discouraged residents. “The vilification of public health and [of] infectious disease experts like Dr. Fauci by significant portions of our society can be demoralizing,” he said. “People might say, ‘Why would I want to put myself through that?’ ”

But Dr. Armstrong doubts this is the case. “I’ve never had a resident tell me that was on their radar screen,” she said, noting that while there had been recent improvements in applicants, lower match numbers for ID fellowships have been a long-standing issue.
 

Rethinking reimbursement

Experts agree that pay issues need to be addressed to make ID a more attractive specialty. Moving away from traditional payment plans to value-based models using quality measurements specific to infectious disease could be one way to quantify the value of ID specialists in care systems.

The Infectious Diseases Society of America recently met with the panel that sets compensation rates for Medicare to discuss ways to increase compensation for ID, said IDSA president Carlos del Rio, MD. He is also a professor of medicine at Emory University.

ID specialists need to be able to put a dollar value to their policy work that’s not related to patient reimbursement, Dr. del Rio said. IDSA’s ongoing compensation initiative advocates for value-based care and provides salary negotiation tools for ID specialists, he added.

“Salaries shouldn’t simply be defined by what reimbursement is, and that’s true for other specialties,” such as hospital medicine and palliative care at many institutions, Dr. Armstrong said. “Infectious disease needs to be held at the same level of respect and value.”

But despite issues within the specialties, ID physicians remain passionate about their field.

“It is the most fascinating specialty I can ever imagine,” Dr. Armstrong said. Dr. Bourque agreed, noting the dynamic nature of specialty, with the emergence of new diseases like COVID-19 and reemergence of diseases like mpox (formerly called monkeypox), Zika, Ebola, and chikungunya in the past decade.

“There’s nothing about the field of infectious diseases that, in my mind, isn’t fascinating or rewarding enough to bring people in,” added Dr. Diekema. “The factors that are keeping people out are primarily economic factors and aspects of our health care system that need attention.”

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

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

NEW ORLEANS – Researchers are calling for a revision of neonatal guidelines in light of new study results from Canada showing that most extremely premature infants fed with formula failed to absorb enough iron.

“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.

courtesy of ASH

According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.

“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”

For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.

The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”

Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.

The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.

“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.

As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.

In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.

Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.

Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.

 


 

Zanubrutinib (Brukinsa) demonstrated superior efficacy and safety over ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to results of the randomized, phase 3 ALPINE study.

Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.

Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.

Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.

“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.

Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.

But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.

The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”

The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
 

Improved safety, efficacy

Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.

Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.

In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.

By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.

In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.

With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.

Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.

However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.

Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.

Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
 

Impressive benefit

The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.

“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview

However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.

In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.

“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”

Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.

Zanubrutinib (Brukinsa) demonstrated superior efficacy and safety over ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to results of the randomized, phase 3 ALPINE study.

Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.

Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.

Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.

“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.

Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.

But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.

The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”

The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
 

Improved safety, efficacy

Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.

Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.

In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.

By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.

In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.

With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.

Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.

However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.

Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.

Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
 

Impressive benefit

The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.

“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview

However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.

In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.

“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”

Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.

Zanubrutinib (Brukinsa) demonstrated superior efficacy and safety over ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to results of the randomized, phase 3 ALPINE study.

Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.

Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.

Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.

“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.

Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.

But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.

The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”

The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
 

Improved safety, efficacy

Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.

Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.

In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.

By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.

In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.

With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.

Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.

However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.

Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.

Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
 

Impressive benefit

The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.

“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview

However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.

In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.

“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”

Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.