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Malpractice lawsuits over denied abortion care may be on the horizon
Some experts predict those providers could soon face a new legal threat: medical malpractice lawsuits alleging they harmed patients by failing to provide timely, necessary abortion care.
“We will absolutely see medical malpractice cases emerge,” said Diana Nordlund, an emergency physician in Grand Rapids, Mich., and former malpractice defense attorney, who chairs the Medical-Legal Committee of the American College of Emergency Physicians. When physicians decide not to provide treatments widely accepted as the standard of care because of these new laws, “that’s perceived as substandard care and there is increased civil liability.”
To some physicians and malpractice attorneys, the question is when – not if – a pregnant patient will die from lack of care and set the stage for a big-dollar wrongful death claim. Abortion rights supporters said such a case could pressure doctors and hospitals to provide appropriate abortion care, counterbalancing their fears of running afoul of state abortion bans, many of which call for criminal prosecution and revocation of medical licenses as punishment for violations.
“If we want to encourage proper care, there has to be some sort of counter-risk to physicians and hospitals for refusing to provide care that should be legal,” said Greer Donley, an associate professor at the University of Pittsburgh school of law who studies the impact of abortion bans. “But most rational people would be more afraid of going to jail.”
Some supporters of abortion bans said they would welcome malpractice lawsuits. Providers are refusing to use the exceptions in some state laws that allow them to perform abortions to save a patient’s life or health, they said.
“It could help achieve our goal if it clarifies that the law did not contradict standard medical practice,” said John Seago, president of Texas Right to Life, referring to the state’s abortion ban.
A new KFF poll found that 59% of ob.gyns. practicing in states with gestational limits on abortion, and 61% of those in states with bans, are somewhat or very concerned about their legal risk when making decisions about the necessity of an abortion.
Some attorneys are exploring lawsuits on behalf of women who they said have been harmed by a state abortion ban. An attorney for Mylissa Farmer, a Missouri woman who was refused an abortion at two hospitals in August after her water broke about 18 weeks into her pregnancy, said she may sue for malpractice. Missouri’s abortion ban, which took effect last year, makes an exception for medical emergencies.
The federal government recently found that the two hospitals violated a federal emergency care law in denying Ms. Farmer an abortion, which experts said could strengthen a malpractice claim. One of the hospitals, Freeman Health System in Joplin, Mo., did not respond to a request for comment. The other, the University of Kansas Health System in Kansas City, said the care provided “was reviewed by the hospital and found to be in accordance with hospital policy,” according to a spokesperson, Jill Chadwick.
Ms. Farmer “experienced permanent physical and emotional damage,” said Michelle Banker, one of her lawyers at the National Women’s Law Center, who added that Ms. Farmer and her attorneys are “considering all our legal options.”
News reports and medical studies show that some women with pregnancy complications have suffered serious health consequences when doctors and hospitals did not provide once-routine abortion care.
Last month, researchers released a study identifying dozens of cases in 14 states in which physicians said deficiencies in care due to abortion restrictions led to preventable complications and hospitalizations, with some patients nearly dying.
“The patients were sent home and told to come back when they had signs of infection,” said Daniel Grossman, an ob.gyn. at the University of California, San Francisco, who led the study. “Many developed serious infections. And it’s clear many of these cases were very emotionally traumatic.”
He said though the researchers did not track patient outcomes, the lack of timely abortion care in such cases could result in severe health harms including loss of fertility, stroke, or heart attack.
“It’s just a matter of time before there will be a death that comes to light,” Dr. Grossman said.
Still, considering the conflict for doctors between medical ethics and personal risk, some stakeholders said patients may be reluctant to sue doctors and juries may balk at finding them liable.
“It’s a terrible position that providers are being put into, and I don’t think juries will blame the doctor unless it’s a super clear case,” said Morgan Murphy, a malpractice plaintiff’s attorney in Missouri.
She said her firm will not pursue malpractice cases based on abortion denials except in “pretty extreme” situations, such as when a patient dies. “Unless a mother is on her deathbed, it’s pretty hard to fault a provider who thinks if they provide treatment they’re going to be criminally liable or will lose their medical license.”
Another hurdle for malpractice cases is that state abortion bans could undermine the argument that abortion is the legal “standard of care,” meaning that it is a widely accepted and prescribed treatment for pregnancy complications such as miscarriage and for fatal fetal abnormalities.
“I absolutely see a breach of the standard of care in these cases,” said Maria A. Phillis, an ob.gyn. and former lawyer in Cleveland. “But if someone goes to trial in a malpractice case, it will come down to a battle of medical experts about whether it’s no longer the standard of care, and the jury would have to decide.”
An additional justification for physicians not to provide abortions is that medical liability insurers generally do not cover damages from criminal acts, which “puts the finger on the scales even more to not do anything,” Dr. Phillis said.
Stuart Grossman, a prominent malpractice plaintiff’s attorney in Florida, said he would be eager to take an abortion-denial case in which the woman suffered serious health or emotional injuries.
Unlike other states with abortion bans, Florida does not cap damage amounts for pain and suffering in malpractice cases, making it more financially viable to sue there.
Mr. Grossman cited the case of Deborah Dorbert, a Florida woman who reportedly was denied an abortion despite being told by her physicians at 24 weeks of pregnancy that her fetus, with no kidneys and underdeveloped lungs, had a fatal condition called Potter syndrome.
Her doctors and the hospital refused to end the pregnancy even though the state’s abortion ban has an exception for fatal fetal abnormalities. Months later, her baby died in his parents’ arms shortly after birth.
“You can see how she’s been devastated mentally,” Mr. Grossman said. “She has a wrongful death case that I’d take in a minute.” He said the couple could file a malpractice suit for Ms. Dorbert’s physical and emotional damages and a separate malpractice and wrongful death suit for the couple’s suffering over the infant’s death.
Failing to counsel patients about their options and connect them with providers willing to terminate a pregnancy is also possible grounds for a malpractice suit, attorneys said. Katie Watson, an associate professor at Northwestern University, Chicago’s school of medicine who has studied state abortion bans, said counseling and referral are not prohibited under these laws and that physicians have an ethical obligation to offer those services.
“I think breaching the obligation for counseling would make a strong malpractice lawsuit,” she said.
Nancy Davis said she received no counseling or referral assistance last July after her doctors at Woman’s Hospital in Baton Rouge, La., told her 10 weeks into her pregnancy that her fetus would not survive because it was missing the top of its skull, a fatal condition called acrania. She said they recommended that she terminate the pregnancy and she agreed.
Ms. Davis said her doctors then told her a hospital executive had denied permission for the procedure because of Louisiana’s abortion ban, even though the law has an exception for fatal fetal abnormalities. A hospital spokesperson declined to comment.
Ms. Davis, who has three children, contacted Planned Parenthood of Greater New York, which arranged for child care and a flight to New York. She had an abortion performed there in September.
“The whole situation has been mentally and physically draining, and my family and I are receiving counseling,” Ms. Davis said. “I’m still very angry at the hospital and the doctors. I feel like I’m owed compensation for the trauma and the heartbreak.”
She sought the counsel of Benjamin Crump, a prominent attorney known for pursuing high-profile cases like wrongful death lawsuits on behalf of the families of Trayvon Martin and George Floyd.
But Mr. Crump said that after studying Ms. Davis’ legal options, he decided a judge would likely dismiss a malpractice suit and that Ms. Davis could end up paying the defendants’ legal fees and costs.
“The doctor’s lawyers will say, ‘You can’t expect my client to break the law and go to prison for up to 25 years,’ ” Mr. Crump said. “Unless you change the law, there is no option for her to receive compensation.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
Some experts predict those providers could soon face a new legal threat: medical malpractice lawsuits alleging they harmed patients by failing to provide timely, necessary abortion care.
“We will absolutely see medical malpractice cases emerge,” said Diana Nordlund, an emergency physician in Grand Rapids, Mich., and former malpractice defense attorney, who chairs the Medical-Legal Committee of the American College of Emergency Physicians. When physicians decide not to provide treatments widely accepted as the standard of care because of these new laws, “that’s perceived as substandard care and there is increased civil liability.”
To some physicians and malpractice attorneys, the question is when – not if – a pregnant patient will die from lack of care and set the stage for a big-dollar wrongful death claim. Abortion rights supporters said such a case could pressure doctors and hospitals to provide appropriate abortion care, counterbalancing their fears of running afoul of state abortion bans, many of which call for criminal prosecution and revocation of medical licenses as punishment for violations.
“If we want to encourage proper care, there has to be some sort of counter-risk to physicians and hospitals for refusing to provide care that should be legal,” said Greer Donley, an associate professor at the University of Pittsburgh school of law who studies the impact of abortion bans. “But most rational people would be more afraid of going to jail.”
Some supporters of abortion bans said they would welcome malpractice lawsuits. Providers are refusing to use the exceptions in some state laws that allow them to perform abortions to save a patient’s life or health, they said.
“It could help achieve our goal if it clarifies that the law did not contradict standard medical practice,” said John Seago, president of Texas Right to Life, referring to the state’s abortion ban.
A new KFF poll found that 59% of ob.gyns. practicing in states with gestational limits on abortion, and 61% of those in states with bans, are somewhat or very concerned about their legal risk when making decisions about the necessity of an abortion.
Some attorneys are exploring lawsuits on behalf of women who they said have been harmed by a state abortion ban. An attorney for Mylissa Farmer, a Missouri woman who was refused an abortion at two hospitals in August after her water broke about 18 weeks into her pregnancy, said she may sue for malpractice. Missouri’s abortion ban, which took effect last year, makes an exception for medical emergencies.
The federal government recently found that the two hospitals violated a federal emergency care law in denying Ms. Farmer an abortion, which experts said could strengthen a malpractice claim. One of the hospitals, Freeman Health System in Joplin, Mo., did not respond to a request for comment. The other, the University of Kansas Health System in Kansas City, said the care provided “was reviewed by the hospital and found to be in accordance with hospital policy,” according to a spokesperson, Jill Chadwick.
Ms. Farmer “experienced permanent physical and emotional damage,” said Michelle Banker, one of her lawyers at the National Women’s Law Center, who added that Ms. Farmer and her attorneys are “considering all our legal options.”
News reports and medical studies show that some women with pregnancy complications have suffered serious health consequences when doctors and hospitals did not provide once-routine abortion care.
Last month, researchers released a study identifying dozens of cases in 14 states in which physicians said deficiencies in care due to abortion restrictions led to preventable complications and hospitalizations, with some patients nearly dying.
“The patients were sent home and told to come back when they had signs of infection,” said Daniel Grossman, an ob.gyn. at the University of California, San Francisco, who led the study. “Many developed serious infections. And it’s clear many of these cases were very emotionally traumatic.”
He said though the researchers did not track patient outcomes, the lack of timely abortion care in such cases could result in severe health harms including loss of fertility, stroke, or heart attack.
“It’s just a matter of time before there will be a death that comes to light,” Dr. Grossman said.
Still, considering the conflict for doctors between medical ethics and personal risk, some stakeholders said patients may be reluctant to sue doctors and juries may balk at finding them liable.
“It’s a terrible position that providers are being put into, and I don’t think juries will blame the doctor unless it’s a super clear case,” said Morgan Murphy, a malpractice plaintiff’s attorney in Missouri.
She said her firm will not pursue malpractice cases based on abortion denials except in “pretty extreme” situations, such as when a patient dies. “Unless a mother is on her deathbed, it’s pretty hard to fault a provider who thinks if they provide treatment they’re going to be criminally liable or will lose their medical license.”
Another hurdle for malpractice cases is that state abortion bans could undermine the argument that abortion is the legal “standard of care,” meaning that it is a widely accepted and prescribed treatment for pregnancy complications such as miscarriage and for fatal fetal abnormalities.
“I absolutely see a breach of the standard of care in these cases,” said Maria A. Phillis, an ob.gyn. and former lawyer in Cleveland. “But if someone goes to trial in a malpractice case, it will come down to a battle of medical experts about whether it’s no longer the standard of care, and the jury would have to decide.”
An additional justification for physicians not to provide abortions is that medical liability insurers generally do not cover damages from criminal acts, which “puts the finger on the scales even more to not do anything,” Dr. Phillis said.
Stuart Grossman, a prominent malpractice plaintiff’s attorney in Florida, said he would be eager to take an abortion-denial case in which the woman suffered serious health or emotional injuries.
Unlike other states with abortion bans, Florida does not cap damage amounts for pain and suffering in malpractice cases, making it more financially viable to sue there.
Mr. Grossman cited the case of Deborah Dorbert, a Florida woman who reportedly was denied an abortion despite being told by her physicians at 24 weeks of pregnancy that her fetus, with no kidneys and underdeveloped lungs, had a fatal condition called Potter syndrome.
Her doctors and the hospital refused to end the pregnancy even though the state’s abortion ban has an exception for fatal fetal abnormalities. Months later, her baby died in his parents’ arms shortly after birth.
“You can see how she’s been devastated mentally,” Mr. Grossman said. “She has a wrongful death case that I’d take in a minute.” He said the couple could file a malpractice suit for Ms. Dorbert’s physical and emotional damages and a separate malpractice and wrongful death suit for the couple’s suffering over the infant’s death.
Failing to counsel patients about their options and connect them with providers willing to terminate a pregnancy is also possible grounds for a malpractice suit, attorneys said. Katie Watson, an associate professor at Northwestern University, Chicago’s school of medicine who has studied state abortion bans, said counseling and referral are not prohibited under these laws and that physicians have an ethical obligation to offer those services.
“I think breaching the obligation for counseling would make a strong malpractice lawsuit,” she said.
Nancy Davis said she received no counseling or referral assistance last July after her doctors at Woman’s Hospital in Baton Rouge, La., told her 10 weeks into her pregnancy that her fetus would not survive because it was missing the top of its skull, a fatal condition called acrania. She said they recommended that she terminate the pregnancy and she agreed.
Ms. Davis said her doctors then told her a hospital executive had denied permission for the procedure because of Louisiana’s abortion ban, even though the law has an exception for fatal fetal abnormalities. A hospital spokesperson declined to comment.
Ms. Davis, who has three children, contacted Planned Parenthood of Greater New York, which arranged for child care and a flight to New York. She had an abortion performed there in September.
“The whole situation has been mentally and physically draining, and my family and I are receiving counseling,” Ms. Davis said. “I’m still very angry at the hospital and the doctors. I feel like I’m owed compensation for the trauma and the heartbreak.”
She sought the counsel of Benjamin Crump, a prominent attorney known for pursuing high-profile cases like wrongful death lawsuits on behalf of the families of Trayvon Martin and George Floyd.
But Mr. Crump said that after studying Ms. Davis’ legal options, he decided a judge would likely dismiss a malpractice suit and that Ms. Davis could end up paying the defendants’ legal fees and costs.
“The doctor’s lawyers will say, ‘You can’t expect my client to break the law and go to prison for up to 25 years,’ ” Mr. Crump said. “Unless you change the law, there is no option for her to receive compensation.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
Some experts predict those providers could soon face a new legal threat: medical malpractice lawsuits alleging they harmed patients by failing to provide timely, necessary abortion care.
“We will absolutely see medical malpractice cases emerge,” said Diana Nordlund, an emergency physician in Grand Rapids, Mich., and former malpractice defense attorney, who chairs the Medical-Legal Committee of the American College of Emergency Physicians. When physicians decide not to provide treatments widely accepted as the standard of care because of these new laws, “that’s perceived as substandard care and there is increased civil liability.”
To some physicians and malpractice attorneys, the question is when – not if – a pregnant patient will die from lack of care and set the stage for a big-dollar wrongful death claim. Abortion rights supporters said such a case could pressure doctors and hospitals to provide appropriate abortion care, counterbalancing their fears of running afoul of state abortion bans, many of which call for criminal prosecution and revocation of medical licenses as punishment for violations.
“If we want to encourage proper care, there has to be some sort of counter-risk to physicians and hospitals for refusing to provide care that should be legal,” said Greer Donley, an associate professor at the University of Pittsburgh school of law who studies the impact of abortion bans. “But most rational people would be more afraid of going to jail.”
Some supporters of abortion bans said they would welcome malpractice lawsuits. Providers are refusing to use the exceptions in some state laws that allow them to perform abortions to save a patient’s life or health, they said.
“It could help achieve our goal if it clarifies that the law did not contradict standard medical practice,” said John Seago, president of Texas Right to Life, referring to the state’s abortion ban.
A new KFF poll found that 59% of ob.gyns. practicing in states with gestational limits on abortion, and 61% of those in states with bans, are somewhat or very concerned about their legal risk when making decisions about the necessity of an abortion.
Some attorneys are exploring lawsuits on behalf of women who they said have been harmed by a state abortion ban. An attorney for Mylissa Farmer, a Missouri woman who was refused an abortion at two hospitals in August after her water broke about 18 weeks into her pregnancy, said she may sue for malpractice. Missouri’s abortion ban, which took effect last year, makes an exception for medical emergencies.
The federal government recently found that the two hospitals violated a federal emergency care law in denying Ms. Farmer an abortion, which experts said could strengthen a malpractice claim. One of the hospitals, Freeman Health System in Joplin, Mo., did not respond to a request for comment. The other, the University of Kansas Health System in Kansas City, said the care provided “was reviewed by the hospital and found to be in accordance with hospital policy,” according to a spokesperson, Jill Chadwick.
Ms. Farmer “experienced permanent physical and emotional damage,” said Michelle Banker, one of her lawyers at the National Women’s Law Center, who added that Ms. Farmer and her attorneys are “considering all our legal options.”
News reports and medical studies show that some women with pregnancy complications have suffered serious health consequences when doctors and hospitals did not provide once-routine abortion care.
Last month, researchers released a study identifying dozens of cases in 14 states in which physicians said deficiencies in care due to abortion restrictions led to preventable complications and hospitalizations, with some patients nearly dying.
“The patients were sent home and told to come back when they had signs of infection,” said Daniel Grossman, an ob.gyn. at the University of California, San Francisco, who led the study. “Many developed serious infections. And it’s clear many of these cases were very emotionally traumatic.”
He said though the researchers did not track patient outcomes, the lack of timely abortion care in such cases could result in severe health harms including loss of fertility, stroke, or heart attack.
“It’s just a matter of time before there will be a death that comes to light,” Dr. Grossman said.
Still, considering the conflict for doctors between medical ethics and personal risk, some stakeholders said patients may be reluctant to sue doctors and juries may balk at finding them liable.
“It’s a terrible position that providers are being put into, and I don’t think juries will blame the doctor unless it’s a super clear case,” said Morgan Murphy, a malpractice plaintiff’s attorney in Missouri.
She said her firm will not pursue malpractice cases based on abortion denials except in “pretty extreme” situations, such as when a patient dies. “Unless a mother is on her deathbed, it’s pretty hard to fault a provider who thinks if they provide treatment they’re going to be criminally liable or will lose their medical license.”
Another hurdle for malpractice cases is that state abortion bans could undermine the argument that abortion is the legal “standard of care,” meaning that it is a widely accepted and prescribed treatment for pregnancy complications such as miscarriage and for fatal fetal abnormalities.
“I absolutely see a breach of the standard of care in these cases,” said Maria A. Phillis, an ob.gyn. and former lawyer in Cleveland. “But if someone goes to trial in a malpractice case, it will come down to a battle of medical experts about whether it’s no longer the standard of care, and the jury would have to decide.”
An additional justification for physicians not to provide abortions is that medical liability insurers generally do not cover damages from criminal acts, which “puts the finger on the scales even more to not do anything,” Dr. Phillis said.
Stuart Grossman, a prominent malpractice plaintiff’s attorney in Florida, said he would be eager to take an abortion-denial case in which the woman suffered serious health or emotional injuries.
Unlike other states with abortion bans, Florida does not cap damage amounts for pain and suffering in malpractice cases, making it more financially viable to sue there.
Mr. Grossman cited the case of Deborah Dorbert, a Florida woman who reportedly was denied an abortion despite being told by her physicians at 24 weeks of pregnancy that her fetus, with no kidneys and underdeveloped lungs, had a fatal condition called Potter syndrome.
Her doctors and the hospital refused to end the pregnancy even though the state’s abortion ban has an exception for fatal fetal abnormalities. Months later, her baby died in his parents’ arms shortly after birth.
“You can see how she’s been devastated mentally,” Mr. Grossman said. “She has a wrongful death case that I’d take in a minute.” He said the couple could file a malpractice suit for Ms. Dorbert’s physical and emotional damages and a separate malpractice and wrongful death suit for the couple’s suffering over the infant’s death.
Failing to counsel patients about their options and connect them with providers willing to terminate a pregnancy is also possible grounds for a malpractice suit, attorneys said. Katie Watson, an associate professor at Northwestern University, Chicago’s school of medicine who has studied state abortion bans, said counseling and referral are not prohibited under these laws and that physicians have an ethical obligation to offer those services.
“I think breaching the obligation for counseling would make a strong malpractice lawsuit,” she said.
Nancy Davis said she received no counseling or referral assistance last July after her doctors at Woman’s Hospital in Baton Rouge, La., told her 10 weeks into her pregnancy that her fetus would not survive because it was missing the top of its skull, a fatal condition called acrania. She said they recommended that she terminate the pregnancy and she agreed.
Ms. Davis said her doctors then told her a hospital executive had denied permission for the procedure because of Louisiana’s abortion ban, even though the law has an exception for fatal fetal abnormalities. A hospital spokesperson declined to comment.
Ms. Davis, who has three children, contacted Planned Parenthood of Greater New York, which arranged for child care and a flight to New York. She had an abortion performed there in September.
“The whole situation has been mentally and physically draining, and my family and I are receiving counseling,” Ms. Davis said. “I’m still very angry at the hospital and the doctors. I feel like I’m owed compensation for the trauma and the heartbreak.”
She sought the counsel of Benjamin Crump, a prominent attorney known for pursuing high-profile cases like wrongful death lawsuits on behalf of the families of Trayvon Martin and George Floyd.
But Mr. Crump said that after studying Ms. Davis’ legal options, he decided a judge would likely dismiss a malpractice suit and that Ms. Davis could end up paying the defendants’ legal fees and costs.
“The doctor’s lawyers will say, ‘You can’t expect my client to break the law and go to prison for up to 25 years,’ ” Mr. Crump said. “Unless you change the law, there is no option for her to receive compensation.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
Pharmacotherapy underprescribed for alcohol use disorder
Health care providers are missing opportunities to give medical treatment to high-risk individuals hospitalized for alcohol use disorder (AUD), a national analysis of Medicare beneficiaries reported.
Increasing such patients’ access to psychiatric care and addiction medicine, as well as encouraging medication prescribing by generalists and nonaddiction specialists, are remedial strategies recommended by lead author Eden Y. Bernstein, MD, of the division of general internal medicine at Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues.
“Hospitalizations for alcohol use disorder are common,” Dr. Bernstein said in an interview. “Our work shows they represent an underutilized opportunity to engage patients with appropriate treatment, including initiation of medications for alcohol use disorder.”
There is a pressing need for such treatment strategies since 29 million U.S. adults have AUD, and alcohol contributes to more than 140,000 deaths annually, the authors noted.
Rarely initiated either at hospital discharge or during follow-up care, medical therapy for AUD was more likely to be provided to younger patients and those involved with psychiatric care or addiction medicine, Dr. Bernstein’s group reported in Annals of Internal Medicine.Hospital admissions, they argued, give patients more access to clinicians and social workers and the vulnerability experienced during hospitalization may motivate behavioral change.
National study
The cohort included 28,601 AUD hospitalizations for 20,401 unique Medicare patients from 2015 to 2017. About 30% of admissions were for women and about 72% for non-Hispanic Blacks. Discharge initiation of medication for AUD was defined as a pharmacy claim for naltrexone, acamprosate, or disulfiram from the day before discharge to 2 days after.
Overall, just 206 patients (0.7%) initiated medication for AUD within 2 days of discharge and 364 (1.3%) started it within 30 days. Among those discharged with a primary diagnosis of AUD, only 70 (2.3%) started medical therapy within 2 days.
The most predictive demographic factor for discharge medication for AUD was younger age: 18-39 years versus 75 years and older (adjusted odds ratio, 3.87; 95% confidence interval, 1.34-11.16).
Initiation of medication for AUD should involve a long-term treatment plan, according to Dr. Bernstein’s group, and if that is not feasible during hospitalization, patients should be referred for outpatient treatment.
An accompanying editorial agrees that the results offer strong evidence of a missed opportunity to address AUD at a potential flexion point. “Hospitalization is a critical touch point for identifying and treating AUD,” wrote Michael F. Mayo-Smith, MD, MPH, of White River Junction (Vt.) VA Medical Center, and Geisel School of Medicine at Dartmouth, Hanover, N.H., and David Lawrence, MD, of the VA Greater Los Angeles Healthcare System and the University of California, Los Angeles.
An intentional discharge protocol can be effective, they noted, as evidenced by a 2014 report in which this approach increased medication-assisted treatment from 0% to 64% in tandem with a decrease in all-cause, 30-day readmission rates.
“There is also growing interest in inpatient addiction consultation services, which have shown [medication] for AUD treatment initiation rates of up to 70% as well as improved engagement in posthospital treatment,” Dr. Mayo-Smith and Dr. Lawrence wrote.
Minority populations need particular attention, they added. “Unfortunately, the availability of evidence-based treatments for AUD does not by itself lead to improved care. We need strategies for widespread adoption so that patients can realize the benefits of these treatments.”
Dr. Bernstein reported funding support from a National Research Service Award and the Massachusetts General Hospital division of general internal medicine; he disclosed fees from Alosa Health. One coauthor was supported by the Agency for Healthcare Research and Quality. Another was supported by the National Institute on Aging and reported relationships with the American College of Cardiology, Boston OIAC Pepper Center, American Heart Association, and US Deprescribing Research Network. Dr. Mayo-Smith disclosed no competing interests. Dr. Lawrence reported fees related to presentations at DDW 2023 and the California Society of Addiction Medicine 2022.
Health care providers are missing opportunities to give medical treatment to high-risk individuals hospitalized for alcohol use disorder (AUD), a national analysis of Medicare beneficiaries reported.
Increasing such patients’ access to psychiatric care and addiction medicine, as well as encouraging medication prescribing by generalists and nonaddiction specialists, are remedial strategies recommended by lead author Eden Y. Bernstein, MD, of the division of general internal medicine at Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues.
“Hospitalizations for alcohol use disorder are common,” Dr. Bernstein said in an interview. “Our work shows they represent an underutilized opportunity to engage patients with appropriate treatment, including initiation of medications for alcohol use disorder.”
There is a pressing need for such treatment strategies since 29 million U.S. adults have AUD, and alcohol contributes to more than 140,000 deaths annually, the authors noted.
Rarely initiated either at hospital discharge or during follow-up care, medical therapy for AUD was more likely to be provided to younger patients and those involved with psychiatric care or addiction medicine, Dr. Bernstein’s group reported in Annals of Internal Medicine.Hospital admissions, they argued, give patients more access to clinicians and social workers and the vulnerability experienced during hospitalization may motivate behavioral change.
National study
The cohort included 28,601 AUD hospitalizations for 20,401 unique Medicare patients from 2015 to 2017. About 30% of admissions were for women and about 72% for non-Hispanic Blacks. Discharge initiation of medication for AUD was defined as a pharmacy claim for naltrexone, acamprosate, or disulfiram from the day before discharge to 2 days after.
Overall, just 206 patients (0.7%) initiated medication for AUD within 2 days of discharge and 364 (1.3%) started it within 30 days. Among those discharged with a primary diagnosis of AUD, only 70 (2.3%) started medical therapy within 2 days.
The most predictive demographic factor for discharge medication for AUD was younger age: 18-39 years versus 75 years and older (adjusted odds ratio, 3.87; 95% confidence interval, 1.34-11.16).
Initiation of medication for AUD should involve a long-term treatment plan, according to Dr. Bernstein’s group, and if that is not feasible during hospitalization, patients should be referred for outpatient treatment.
An accompanying editorial agrees that the results offer strong evidence of a missed opportunity to address AUD at a potential flexion point. “Hospitalization is a critical touch point for identifying and treating AUD,” wrote Michael F. Mayo-Smith, MD, MPH, of White River Junction (Vt.) VA Medical Center, and Geisel School of Medicine at Dartmouth, Hanover, N.H., and David Lawrence, MD, of the VA Greater Los Angeles Healthcare System and the University of California, Los Angeles.
An intentional discharge protocol can be effective, they noted, as evidenced by a 2014 report in which this approach increased medication-assisted treatment from 0% to 64% in tandem with a decrease in all-cause, 30-day readmission rates.
“There is also growing interest in inpatient addiction consultation services, which have shown [medication] for AUD treatment initiation rates of up to 70% as well as improved engagement in posthospital treatment,” Dr. Mayo-Smith and Dr. Lawrence wrote.
Minority populations need particular attention, they added. “Unfortunately, the availability of evidence-based treatments for AUD does not by itself lead to improved care. We need strategies for widespread adoption so that patients can realize the benefits of these treatments.”
Dr. Bernstein reported funding support from a National Research Service Award and the Massachusetts General Hospital division of general internal medicine; he disclosed fees from Alosa Health. One coauthor was supported by the Agency for Healthcare Research and Quality. Another was supported by the National Institute on Aging and reported relationships with the American College of Cardiology, Boston OIAC Pepper Center, American Heart Association, and US Deprescribing Research Network. Dr. Mayo-Smith disclosed no competing interests. Dr. Lawrence reported fees related to presentations at DDW 2023 and the California Society of Addiction Medicine 2022.
Health care providers are missing opportunities to give medical treatment to high-risk individuals hospitalized for alcohol use disorder (AUD), a national analysis of Medicare beneficiaries reported.
Increasing such patients’ access to psychiatric care and addiction medicine, as well as encouraging medication prescribing by generalists and nonaddiction specialists, are remedial strategies recommended by lead author Eden Y. Bernstein, MD, of the division of general internal medicine at Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues.
“Hospitalizations for alcohol use disorder are common,” Dr. Bernstein said in an interview. “Our work shows they represent an underutilized opportunity to engage patients with appropriate treatment, including initiation of medications for alcohol use disorder.”
There is a pressing need for such treatment strategies since 29 million U.S. adults have AUD, and alcohol contributes to more than 140,000 deaths annually, the authors noted.
Rarely initiated either at hospital discharge or during follow-up care, medical therapy for AUD was more likely to be provided to younger patients and those involved with psychiatric care or addiction medicine, Dr. Bernstein’s group reported in Annals of Internal Medicine.Hospital admissions, they argued, give patients more access to clinicians and social workers and the vulnerability experienced during hospitalization may motivate behavioral change.
National study
The cohort included 28,601 AUD hospitalizations for 20,401 unique Medicare patients from 2015 to 2017. About 30% of admissions were for women and about 72% for non-Hispanic Blacks. Discharge initiation of medication for AUD was defined as a pharmacy claim for naltrexone, acamprosate, or disulfiram from the day before discharge to 2 days after.
Overall, just 206 patients (0.7%) initiated medication for AUD within 2 days of discharge and 364 (1.3%) started it within 30 days. Among those discharged with a primary diagnosis of AUD, only 70 (2.3%) started medical therapy within 2 days.
The most predictive demographic factor for discharge medication for AUD was younger age: 18-39 years versus 75 years and older (adjusted odds ratio, 3.87; 95% confidence interval, 1.34-11.16).
Initiation of medication for AUD should involve a long-term treatment plan, according to Dr. Bernstein’s group, and if that is not feasible during hospitalization, patients should be referred for outpatient treatment.
An accompanying editorial agrees that the results offer strong evidence of a missed opportunity to address AUD at a potential flexion point. “Hospitalization is a critical touch point for identifying and treating AUD,” wrote Michael F. Mayo-Smith, MD, MPH, of White River Junction (Vt.) VA Medical Center, and Geisel School of Medicine at Dartmouth, Hanover, N.H., and David Lawrence, MD, of the VA Greater Los Angeles Healthcare System and the University of California, Los Angeles.
An intentional discharge protocol can be effective, they noted, as evidenced by a 2014 report in which this approach increased medication-assisted treatment from 0% to 64% in tandem with a decrease in all-cause, 30-day readmission rates.
“There is also growing interest in inpatient addiction consultation services, which have shown [medication] for AUD treatment initiation rates of up to 70% as well as improved engagement in posthospital treatment,” Dr. Mayo-Smith and Dr. Lawrence wrote.
Minority populations need particular attention, they added. “Unfortunately, the availability of evidence-based treatments for AUD does not by itself lead to improved care. We need strategies for widespread adoption so that patients can realize the benefits of these treatments.”
Dr. Bernstein reported funding support from a National Research Service Award and the Massachusetts General Hospital division of general internal medicine; he disclosed fees from Alosa Health. One coauthor was supported by the Agency for Healthcare Research and Quality. Another was supported by the National Institute on Aging and reported relationships with the American College of Cardiology, Boston OIAC Pepper Center, American Heart Association, and US Deprescribing Research Network. Dr. Mayo-Smith disclosed no competing interests. Dr. Lawrence reported fees related to presentations at DDW 2023 and the California Society of Addiction Medicine 2022.
FROM ANNALS OF INTERNAL MEDICINE
Time for mental stress testing in ANOCA?
, new results show.
Further analysis in the small study suggested that mental stress–induced myocardial ischemia (MSIMI) was not statistically related to coronary microvascular dysfunction (CMD).
“Since the findings do not support a correlation between MSIMI and CMD, which has been a widely accepted mechanistic explanation of ANOCA, routine mental stress testing in patients with ANOCA seems necessary,” researchers led by Qingshan Geng, MD, PhD, of Shenzhen People’s Hospital, Guangdong, China, conclude in a report published online in the Journal of the American College of Cardiology.
Dr. Geng said in an interview that the use of virtual reality devices to administer mental stress tests “ensures standardized experimental procedures, with each participant receiving an objectively equivalent level of stress load.
“The immersive experience provided by VR lowers the environmental requirements for the test,” he noted. “Furthermore, the application of VR reduces the workload of personnel responsible for inducing mental stress, simplifying the experimental process.”
The team also developed a mobile app that enables remote monitoring of participants’ visual experiences during PET/CT scans and facilitates communication, he added.
Mental stress testing and meds?
Both ANOCA and MSIMI in patients with coronary artery disease disproportionately affect women and are associated with poor cardiovascular prognosis, the researchers write.
“However, the role of MSIMI and the exact influence of mental stress in ANOCA have not previously been studied,” they point out.
For this investigation, 84 women with ANOCA and 42 age-matched controls underwent three mental stress challenges delivered via VR.
Tests included mental arithmetic, making a public speech describing a recent emotionally upsetting event, and a task-modified Stroop test, in which participants were asked to say the color in which the word appears, not the color that the word names. For example, if the word “yellow” appears in blue type, blue would be the correct answer.
An adenosine stress test was given 5-8 minutes after the mental stress challenges started, and cardiac PET/CT was used to examine myocardial blood flow and perfusion.
The investigators report that women with ANOCA had a much higher rate of MSIMI (42.9%), compared with control participants (one patient; 2.4%). They also had a higher proportion of coronary microvascular dysfunction (CMD; 24.6% vs. 8.6%), but the occurrence of MSIMI and CMD was not related, the authors note.
Consistent with previous studies, “we observed that CMD is more prevalent in ANOCA women than the age-matched healthy individuals. MSIMI rate, however, was notably higher than the rate of CMD in our female ANOCA population,” they write. “The lack of a significant association between MSIMI and CMD indicates the mechanisms of MSIMI cannot be well explained by the adenosine-induced CMD.”
Dr. Geng suggested that ANOCA patients may benefit from treatment with escitalopram.
“Compelling evidence” from the REMIT randomized, placebo-controlled trial validates the efficacy of the drug as an MSIMI treatment, he said.
Sample size too small?
Asked for comment on the findings, Viola Vaccarino, MD, PhD, Wilton Looney Distinguished Professor of Cardiovascular Research at Emory University’s Rollins School of Public Health and a professor in the university’s School of Medicine, Atlanta, said she disagreed with several aspects of this study and the investigators’ conclusions.
Although the study suggests that MSIMI is prevalent among women with ANOCA, “the sample size was too small to make any definite conclusions,” she said in an interview.
“In fact,” she said, “I do not agree with the authors’ conclusions that MSIMI and CMD were not related, based on the data presented, even though the P value was not significant.”
In addition, more research is needed before screening can be recommended, she said. “The effectiveness of this testing modality in this population should be demonstrated first.”
Furthermore, she added, “an established treatment for MSIMI has yet to be tested in large, controlled trials, which limits the potential clinical benefit that may result from this [screening] test.”
For now, to ameliorate potential MSIMI in women with ANOCA, Dr. Vaccarino recommends behavioral modalities or stress-reduction management techniques, including biofeedback, meditation, breathing exercises, and “just plain regular physical activity,” rather than the use of psychotropic medications.
Dr. Vaccarino’s team has a study underway that builds on earlier work involving more than 900 participants, which showed that MSIMI was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction (hazard ratio, 2.5).
The ongoing study, which investigates the link between emotional stress and heart disease in men and women, should be completed in about 3 years, she said.
Microvascular disease or spasm?
Leslie Cho, MD, chair of the American College of Cardiology’s Cardiovascular Disease in Women Committee, director of the Cleveland Clinic’s Women’s Cardiovascular Center, and professor of medicine at Cleveland Clinic Lerner School of Medicine and Case Western Reserve Medical School, commented on the mental stress–heart connection and mental stress testing for this article.
A “very big flaw” of the JACC study, she said, is that although PET testing can detect microvascular disease, it cannot detect microvascular spasm.
PET can show the coronary flow reserve, “which is a nice way to assess microvascular dysfunction,” she acknowledged, “but it really can’t tell microvascular spasm, because adenosine works in a different pathway than acetylcholine – and I think it’s important for people to have the right diagnosis.
“We do physiologic testing to distinguish the two conditions,” she noted. “We do the gold standard, which is the cath lab.”
“The problem with women with chest pain for years is that they get a stress test, they get a cath, and everything’s normal. Then they get blown off as anxious or whatever.”
Clinicians should conduct the gold standard workup – provocative physiologic testing – for these women who continue to have chest pain when results of other tests are negative, she said. “The test used to be very cumbersome, but today, we have systems that make it super easy to use and to distinguish microvascular disease and microvascular spasm.”
Importantly, she added, physiologic testing should be performed when women are off therapy – something that doesn’t always happen in the clinic.
Regarding treatment, she added, “if you’re having emotional stress, the answer is not another medicine. The answer is cognitive-behavioral therapy or another behavioral intervention to overcome anxiety.”
Tune in and advocate
What can clinicians do for women with ANOCA after testing reveals no significant coronary artery disease or microvascular spasms?
“Very often, it’s a matter of the doctor listening and responding to the patient,” Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital, New York, said in an intereview.
In her practice, Dr. Contreras sees highly stressed women on a daily basis. Many of her patients are women from diverse racial/ethnic groups, often of lower socioeconomic status, who are heads of households, work more than one job, and experience other major stressors.
“My message to clinicians is: don’t give up on a woman just because you looked at the arteries and couldn’t find anything specific. If she keeps coming back with the same symptom, it’s important to address it,” she said. “Maybe it isn’t the symptom. Maybe she needs to talk about her situation, about the physiological and psychosocial factors contributing to the symptom that a test alone won’t reveal.”
Regarding cardiovascular spasms that are identified through physiologic testing, she said, “I don’t know that medications such as SSRIs [selective serotonin reuptake inhibitors] are going to change anything. But many things can be changed by listening or helping the patient to stop and think about her mental health.”
Following up with a referral to a therapist can help, she said; “Take away the mental health stigma by telling the patient that the referral is simply to help her cope.”
Dr. Contreras urges clinicians to be advocates for such patients. If an insurance company says it will cover only three therapy sessions, “tell them that three appointments are not enough” to address multiple issues.
“If we invest money in helping patients identify and cope with these issues, we are likely to get better long-term outcomes, rather than having that woman come into the emergency department with chest pain over and over and doing 20,000 tests that are going to show exactly the same thing,” Dr. Contreras concluded.
Dr. Geng’s study was supported by the High-Level Hospital Construction Project of Guangdong Provincial People’s Hospital, by a grant from Guangdong Provincial Bureau of Traditional Chinese Medicine, and by a grant from Guangdong Medical Science and Technology Research Foundation. The authors, Dr. Vaccarino, Dr. Contreras, and Dr. Cho report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, new results show.
Further analysis in the small study suggested that mental stress–induced myocardial ischemia (MSIMI) was not statistically related to coronary microvascular dysfunction (CMD).
“Since the findings do not support a correlation between MSIMI and CMD, which has been a widely accepted mechanistic explanation of ANOCA, routine mental stress testing in patients with ANOCA seems necessary,” researchers led by Qingshan Geng, MD, PhD, of Shenzhen People’s Hospital, Guangdong, China, conclude in a report published online in the Journal of the American College of Cardiology.
Dr. Geng said in an interview that the use of virtual reality devices to administer mental stress tests “ensures standardized experimental procedures, with each participant receiving an objectively equivalent level of stress load.
“The immersive experience provided by VR lowers the environmental requirements for the test,” he noted. “Furthermore, the application of VR reduces the workload of personnel responsible for inducing mental stress, simplifying the experimental process.”
The team also developed a mobile app that enables remote monitoring of participants’ visual experiences during PET/CT scans and facilitates communication, he added.
Mental stress testing and meds?
Both ANOCA and MSIMI in patients with coronary artery disease disproportionately affect women and are associated with poor cardiovascular prognosis, the researchers write.
“However, the role of MSIMI and the exact influence of mental stress in ANOCA have not previously been studied,” they point out.
For this investigation, 84 women with ANOCA and 42 age-matched controls underwent three mental stress challenges delivered via VR.
Tests included mental arithmetic, making a public speech describing a recent emotionally upsetting event, and a task-modified Stroop test, in which participants were asked to say the color in which the word appears, not the color that the word names. For example, if the word “yellow” appears in blue type, blue would be the correct answer.
An adenosine stress test was given 5-8 minutes after the mental stress challenges started, and cardiac PET/CT was used to examine myocardial blood flow and perfusion.
The investigators report that women with ANOCA had a much higher rate of MSIMI (42.9%), compared with control participants (one patient; 2.4%). They also had a higher proportion of coronary microvascular dysfunction (CMD; 24.6% vs. 8.6%), but the occurrence of MSIMI and CMD was not related, the authors note.
Consistent with previous studies, “we observed that CMD is more prevalent in ANOCA women than the age-matched healthy individuals. MSIMI rate, however, was notably higher than the rate of CMD in our female ANOCA population,” they write. “The lack of a significant association between MSIMI and CMD indicates the mechanisms of MSIMI cannot be well explained by the adenosine-induced CMD.”
Dr. Geng suggested that ANOCA patients may benefit from treatment with escitalopram.
“Compelling evidence” from the REMIT randomized, placebo-controlled trial validates the efficacy of the drug as an MSIMI treatment, he said.
Sample size too small?
Asked for comment on the findings, Viola Vaccarino, MD, PhD, Wilton Looney Distinguished Professor of Cardiovascular Research at Emory University’s Rollins School of Public Health and a professor in the university’s School of Medicine, Atlanta, said she disagreed with several aspects of this study and the investigators’ conclusions.
Although the study suggests that MSIMI is prevalent among women with ANOCA, “the sample size was too small to make any definite conclusions,” she said in an interview.
“In fact,” she said, “I do not agree with the authors’ conclusions that MSIMI and CMD were not related, based on the data presented, even though the P value was not significant.”
In addition, more research is needed before screening can be recommended, she said. “The effectiveness of this testing modality in this population should be demonstrated first.”
Furthermore, she added, “an established treatment for MSIMI has yet to be tested in large, controlled trials, which limits the potential clinical benefit that may result from this [screening] test.”
For now, to ameliorate potential MSIMI in women with ANOCA, Dr. Vaccarino recommends behavioral modalities or stress-reduction management techniques, including biofeedback, meditation, breathing exercises, and “just plain regular physical activity,” rather than the use of psychotropic medications.
Dr. Vaccarino’s team has a study underway that builds on earlier work involving more than 900 participants, which showed that MSIMI was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction (hazard ratio, 2.5).
The ongoing study, which investigates the link between emotional stress and heart disease in men and women, should be completed in about 3 years, she said.
Microvascular disease or spasm?
Leslie Cho, MD, chair of the American College of Cardiology’s Cardiovascular Disease in Women Committee, director of the Cleveland Clinic’s Women’s Cardiovascular Center, and professor of medicine at Cleveland Clinic Lerner School of Medicine and Case Western Reserve Medical School, commented on the mental stress–heart connection and mental stress testing for this article.
A “very big flaw” of the JACC study, she said, is that although PET testing can detect microvascular disease, it cannot detect microvascular spasm.
PET can show the coronary flow reserve, “which is a nice way to assess microvascular dysfunction,” she acknowledged, “but it really can’t tell microvascular spasm, because adenosine works in a different pathway than acetylcholine – and I think it’s important for people to have the right diagnosis.
“We do physiologic testing to distinguish the two conditions,” she noted. “We do the gold standard, which is the cath lab.”
“The problem with women with chest pain for years is that they get a stress test, they get a cath, and everything’s normal. Then they get blown off as anxious or whatever.”
Clinicians should conduct the gold standard workup – provocative physiologic testing – for these women who continue to have chest pain when results of other tests are negative, she said. “The test used to be very cumbersome, but today, we have systems that make it super easy to use and to distinguish microvascular disease and microvascular spasm.”
Importantly, she added, physiologic testing should be performed when women are off therapy – something that doesn’t always happen in the clinic.
Regarding treatment, she added, “if you’re having emotional stress, the answer is not another medicine. The answer is cognitive-behavioral therapy or another behavioral intervention to overcome anxiety.”
Tune in and advocate
What can clinicians do for women with ANOCA after testing reveals no significant coronary artery disease or microvascular spasms?
“Very often, it’s a matter of the doctor listening and responding to the patient,” Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital, New York, said in an intereview.
In her practice, Dr. Contreras sees highly stressed women on a daily basis. Many of her patients are women from diverse racial/ethnic groups, often of lower socioeconomic status, who are heads of households, work more than one job, and experience other major stressors.
“My message to clinicians is: don’t give up on a woman just because you looked at the arteries and couldn’t find anything specific. If she keeps coming back with the same symptom, it’s important to address it,” she said. “Maybe it isn’t the symptom. Maybe she needs to talk about her situation, about the physiological and psychosocial factors contributing to the symptom that a test alone won’t reveal.”
Regarding cardiovascular spasms that are identified through physiologic testing, she said, “I don’t know that medications such as SSRIs [selective serotonin reuptake inhibitors] are going to change anything. But many things can be changed by listening or helping the patient to stop and think about her mental health.”
Following up with a referral to a therapist can help, she said; “Take away the mental health stigma by telling the patient that the referral is simply to help her cope.”
Dr. Contreras urges clinicians to be advocates for such patients. If an insurance company says it will cover only three therapy sessions, “tell them that three appointments are not enough” to address multiple issues.
“If we invest money in helping patients identify and cope with these issues, we are likely to get better long-term outcomes, rather than having that woman come into the emergency department with chest pain over and over and doing 20,000 tests that are going to show exactly the same thing,” Dr. Contreras concluded.
Dr. Geng’s study was supported by the High-Level Hospital Construction Project of Guangdong Provincial People’s Hospital, by a grant from Guangdong Provincial Bureau of Traditional Chinese Medicine, and by a grant from Guangdong Medical Science and Technology Research Foundation. The authors, Dr. Vaccarino, Dr. Contreras, and Dr. Cho report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, new results show.
Further analysis in the small study suggested that mental stress–induced myocardial ischemia (MSIMI) was not statistically related to coronary microvascular dysfunction (CMD).
“Since the findings do not support a correlation between MSIMI and CMD, which has been a widely accepted mechanistic explanation of ANOCA, routine mental stress testing in patients with ANOCA seems necessary,” researchers led by Qingshan Geng, MD, PhD, of Shenzhen People’s Hospital, Guangdong, China, conclude in a report published online in the Journal of the American College of Cardiology.
Dr. Geng said in an interview that the use of virtual reality devices to administer mental stress tests “ensures standardized experimental procedures, with each participant receiving an objectively equivalent level of stress load.
“The immersive experience provided by VR lowers the environmental requirements for the test,” he noted. “Furthermore, the application of VR reduces the workload of personnel responsible for inducing mental stress, simplifying the experimental process.”
The team also developed a mobile app that enables remote monitoring of participants’ visual experiences during PET/CT scans and facilitates communication, he added.
Mental stress testing and meds?
Both ANOCA and MSIMI in patients with coronary artery disease disproportionately affect women and are associated with poor cardiovascular prognosis, the researchers write.
“However, the role of MSIMI and the exact influence of mental stress in ANOCA have not previously been studied,” they point out.
For this investigation, 84 women with ANOCA and 42 age-matched controls underwent three mental stress challenges delivered via VR.
Tests included mental arithmetic, making a public speech describing a recent emotionally upsetting event, and a task-modified Stroop test, in which participants were asked to say the color in which the word appears, not the color that the word names. For example, if the word “yellow” appears in blue type, blue would be the correct answer.
An adenosine stress test was given 5-8 minutes after the mental stress challenges started, and cardiac PET/CT was used to examine myocardial blood flow and perfusion.
The investigators report that women with ANOCA had a much higher rate of MSIMI (42.9%), compared with control participants (one patient; 2.4%). They also had a higher proportion of coronary microvascular dysfunction (CMD; 24.6% vs. 8.6%), but the occurrence of MSIMI and CMD was not related, the authors note.
Consistent with previous studies, “we observed that CMD is more prevalent in ANOCA women than the age-matched healthy individuals. MSIMI rate, however, was notably higher than the rate of CMD in our female ANOCA population,” they write. “The lack of a significant association between MSIMI and CMD indicates the mechanisms of MSIMI cannot be well explained by the adenosine-induced CMD.”
Dr. Geng suggested that ANOCA patients may benefit from treatment with escitalopram.
“Compelling evidence” from the REMIT randomized, placebo-controlled trial validates the efficacy of the drug as an MSIMI treatment, he said.
Sample size too small?
Asked for comment on the findings, Viola Vaccarino, MD, PhD, Wilton Looney Distinguished Professor of Cardiovascular Research at Emory University’s Rollins School of Public Health and a professor in the university’s School of Medicine, Atlanta, said she disagreed with several aspects of this study and the investigators’ conclusions.
Although the study suggests that MSIMI is prevalent among women with ANOCA, “the sample size was too small to make any definite conclusions,” she said in an interview.
“In fact,” she said, “I do not agree with the authors’ conclusions that MSIMI and CMD were not related, based on the data presented, even though the P value was not significant.”
In addition, more research is needed before screening can be recommended, she said. “The effectiveness of this testing modality in this population should be demonstrated first.”
Furthermore, she added, “an established treatment for MSIMI has yet to be tested in large, controlled trials, which limits the potential clinical benefit that may result from this [screening] test.”
For now, to ameliorate potential MSIMI in women with ANOCA, Dr. Vaccarino recommends behavioral modalities or stress-reduction management techniques, including biofeedback, meditation, breathing exercises, and “just plain regular physical activity,” rather than the use of psychotropic medications.
Dr. Vaccarino’s team has a study underway that builds on earlier work involving more than 900 participants, which showed that MSIMI was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction (hazard ratio, 2.5).
The ongoing study, which investigates the link between emotional stress and heart disease in men and women, should be completed in about 3 years, she said.
Microvascular disease or spasm?
Leslie Cho, MD, chair of the American College of Cardiology’s Cardiovascular Disease in Women Committee, director of the Cleveland Clinic’s Women’s Cardiovascular Center, and professor of medicine at Cleveland Clinic Lerner School of Medicine and Case Western Reserve Medical School, commented on the mental stress–heart connection and mental stress testing for this article.
A “very big flaw” of the JACC study, she said, is that although PET testing can detect microvascular disease, it cannot detect microvascular spasm.
PET can show the coronary flow reserve, “which is a nice way to assess microvascular dysfunction,” she acknowledged, “but it really can’t tell microvascular spasm, because adenosine works in a different pathway than acetylcholine – and I think it’s important for people to have the right diagnosis.
“We do physiologic testing to distinguish the two conditions,” she noted. “We do the gold standard, which is the cath lab.”
“The problem with women with chest pain for years is that they get a stress test, they get a cath, and everything’s normal. Then they get blown off as anxious or whatever.”
Clinicians should conduct the gold standard workup – provocative physiologic testing – for these women who continue to have chest pain when results of other tests are negative, she said. “The test used to be very cumbersome, but today, we have systems that make it super easy to use and to distinguish microvascular disease and microvascular spasm.”
Importantly, she added, physiologic testing should be performed when women are off therapy – something that doesn’t always happen in the clinic.
Regarding treatment, she added, “if you’re having emotional stress, the answer is not another medicine. The answer is cognitive-behavioral therapy or another behavioral intervention to overcome anxiety.”
Tune in and advocate
What can clinicians do for women with ANOCA after testing reveals no significant coronary artery disease or microvascular spasms?
“Very often, it’s a matter of the doctor listening and responding to the patient,” Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital, New York, said in an intereview.
In her practice, Dr. Contreras sees highly stressed women on a daily basis. Many of her patients are women from diverse racial/ethnic groups, often of lower socioeconomic status, who are heads of households, work more than one job, and experience other major stressors.
“My message to clinicians is: don’t give up on a woman just because you looked at the arteries and couldn’t find anything specific. If she keeps coming back with the same symptom, it’s important to address it,” she said. “Maybe it isn’t the symptom. Maybe she needs to talk about her situation, about the physiological and psychosocial factors contributing to the symptom that a test alone won’t reveal.”
Regarding cardiovascular spasms that are identified through physiologic testing, she said, “I don’t know that medications such as SSRIs [selective serotonin reuptake inhibitors] are going to change anything. But many things can be changed by listening or helping the patient to stop and think about her mental health.”
Following up with a referral to a therapist can help, she said; “Take away the mental health stigma by telling the patient that the referral is simply to help her cope.”
Dr. Contreras urges clinicians to be advocates for such patients. If an insurance company says it will cover only three therapy sessions, “tell them that three appointments are not enough” to address multiple issues.
“If we invest money in helping patients identify and cope with these issues, we are likely to get better long-term outcomes, rather than having that woman come into the emergency department with chest pain over and over and doing 20,000 tests that are going to show exactly the same thing,” Dr. Contreras concluded.
Dr. Geng’s study was supported by the High-Level Hospital Construction Project of Guangdong Provincial People’s Hospital, by a grant from Guangdong Provincial Bureau of Traditional Chinese Medicine, and by a grant from Guangdong Medical Science and Technology Research Foundation. The authors, Dr. Vaccarino, Dr. Contreras, and Dr. Cho report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAFE algorithm detects liver disease in general population
VIENNA – An algorithm, the Steatosis-Associated Fibrosis Estimator (SAFE), was developed to detect clinically significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). It is effective at detecting chronic liver disease from all causes with or without NAFLD in the general population, according the results of a U.S. population-based study. The algorithm was designed for use in primary care to help slow the steep rise in liver disease burden.
On the basis of the SAFE score, 61.3% of participants were at low risk for clinically significant fibrosis; 11.2% were at high risk; and 27.5% were at intermediate risk. Upon validation, very few of the low-risk participants had liver fibrosis, while nearly a third of those with a high-risk score had clinically significant fibrosis. In addition, a high percentage of the patients with high-risk SAFE scores had viral hepatitis and elevations in ferritin level.
“This is the first time that there has been a test that provides a score to detect low-risk liver disease in primary care,” said Ray Kim, MD, from Stanford (Calif.) University, senior investigator, who was speaking to this news organization at the annual International Liver Congress sponsored by the European Association for the Study of the Liver
“Primary care doctors currently detect liver disease through a serendipitous abnormal finding on ultrasound or blood tests that detect elevated transaminases, and then the patient is referred to a hepatologist, who figures out what is really going on,” said Dr. Kim.
“This approach is limited, so we need to get SAFE into primary care so these doctors can automatically calculate their scores, and if the patient is over 100 [high risk of chronic liver disease], then they need help [referral to a hepatologist].”
Liver deaths sharply rising
Public health data show that more people are dying of liver disease today than previously. Deaths in the United States have doubled over the past 20 years, said Dr. Kim. “If our mission is to help these patients and prevent death, [things are] moving in the wrong direction.”
He stressed that in order to change the direction, “primary care doctors need to engage with the issue and have appropriate tools to identify people with liver disease.”
Most often, the reason for this rise in deaths is that cases are being diagnosed at advanced stages of disease in which reversibility is limited, he added. “We want to move upstream where people might have early-stage disease and where we can intervene and make a difference.”
In an effort to help earlier detection of liver disease, the SAFE score was developed and validated by Dr. Kim and his colleagues to detect clinically significant (greater than stage 2) fibrosis in patients with NAFLD in primary care. The score is based upon age, body mass index, diabetes, platelet level, aspartate and alanine aminotransferase levels, and globulin level. A score of less than zero signifies that a patient is at low risk for liver fibrosis, while a score greater than 100 signifies a high risk of fibrosis. A score between 0 and 99 denotes intermediate risk of fibrosis.
“Unlike other noninvasive tests that detect advanced fibrosis, this one detects early-stage fibrosis. We’ve shown that the SAFE estimator is better than all other blood-based markers,” explained Dr. Kim.
Applying SAFE to the general population
In the study presented here at EASL, Dr. Kim aimed to expand the horizon for SAFE testing to the U.S. general population and to assess whether SAFE was effective in screening for chronic liver disease regardless of steatosis of the liver.
Together with first author Nakia Chung, MD, also from Stanford University, Dr. Kim applied the SAFE score to data from 7,156 participants of the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. NHANES is representative of the noninstitutionalized, civilian population of the United States. It includes broad demographic, clinical, and laboratory data, including transient elastography data. FibroScans were first used in 2017, so the investigators had 3 years of FibroScan data with which to validate the score.
The researchers extrapolated the NHANES sample data to the U.S. population. They found that the proportion of adults with steatosis (CAP score > 274 dB/m) and significant fibrosis (LSM > 8.0 kPa) was 42.7% (95% confidence interval, 41.0%- 44.3%) and 8.9% (7.6%-10.2%), respectively. In addition, 11.3% (10.2%-12.5%) of the adult U.S. population demonstrated a significant amount of alcohol use, 2.3% (1.4%-3.3%) showed evidence of hepatitis B or C, and 5.4% (4.6%-6.2%) had elevated serum ferritin levels.
The researchers then stratified the patients according to previously defined SAFE tiers of low, intermediate, and high risk and projected findings to the U.S. general population.
“When we applied our score to the general population, we found multiple abnormalities in the high-risk groups [SAFE >100] having Fibroscan data that are consistent with stage 2 or higher fibrosis regardless of etiology, “Dr. Kim pointed out.
Results also showed that very few patients with SAFE less than 0 had liver fibrosis (4% among those with liver stiffness measure [LSM] > 8kPa, and 0.8% with LSM > 12kPa). Among those with SAFE > 100, nearly a third (31.5%) had LSM of > 8kPa, and 16.5% had LSM > 12kPa.
In addition to fibrosis, liver abnormalities were common among patients with SAFE greater than 100, including steatosis (68.0%), viral hepatitis (7.0%), and abnormal ferritin levels (12.9%); 10.8% of these patients used alcohol.
“Right now, some patients are referred, but on examination and FibroScan, they might actually be okay, so it it’s a waste of time and money for everyone. We can preempt all of this by doing a blood test and focusing on those people who really need a scan,” said Dr. Kim.
The researcher is now working with primary care colleagues to help further develop and integrate SAFE into the primary care setting.
Fibrosis score in patients with metabolic dysfunction
Also presenting at the same session on population health was Willem Pieter Brouwer, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. He reported results of a validation study of a new risk score – the Metabolic Dysfunction-Associated Fibrosis–5 (MAF-5) score – for use for people with metabolic dysfunction who are recommended for screening for liver fibrosis.
“We believe the MAF-5 score may be a good alternative to the FIB-4 [a liver fibrosis biomarker] for use in the referral pathway for liver health evaluation,” remarked Dr. Brouwer. “The clinical practice guidelines recommend using FIB-4 scores, but these have a poor-moderate performance in the population setting.
“We developed and validated our score in a population of 5,500 from the NHANES 2017-2020 cycle and validated the score in populations from Rotterdam, which is a cohort of elderly participants, and in fibrosis among patients with biopsy-proven NAFLD from Colombia and Belgium,” he explained.
He also validated the score against different existing scoring systems and different methods of measuring liver stiffness and validated it for prognostic use to predict all-cause mortality in the NHANES III cohort.
Dr. Brouwer removed age as a factor of his new MAF-5 score; the score is thus stable for patients of all ages and is suitable for detecting liver disease in younger patients. “This is very important because these patients are currently underserved and have the most years of life to win.”
Referring to the SAFE score discussed by Dr. Kim, as well as other scores, he said, “The FIB-4, SAFE, and NFS [NAFLD fibrosis score] all include age in the scores, which causes problems and limitations in aging populations, as more and more patients will be referred due to an increasing score. Hence, the elderly are mostly all referred for liver checkups.”
Dr. Kim and Dr. Brouwer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA – An algorithm, the Steatosis-Associated Fibrosis Estimator (SAFE), was developed to detect clinically significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). It is effective at detecting chronic liver disease from all causes with or without NAFLD in the general population, according the results of a U.S. population-based study. The algorithm was designed for use in primary care to help slow the steep rise in liver disease burden.
On the basis of the SAFE score, 61.3% of participants were at low risk for clinically significant fibrosis; 11.2% were at high risk; and 27.5% were at intermediate risk. Upon validation, very few of the low-risk participants had liver fibrosis, while nearly a third of those with a high-risk score had clinically significant fibrosis. In addition, a high percentage of the patients with high-risk SAFE scores had viral hepatitis and elevations in ferritin level.
“This is the first time that there has been a test that provides a score to detect low-risk liver disease in primary care,” said Ray Kim, MD, from Stanford (Calif.) University, senior investigator, who was speaking to this news organization at the annual International Liver Congress sponsored by the European Association for the Study of the Liver
“Primary care doctors currently detect liver disease through a serendipitous abnormal finding on ultrasound or blood tests that detect elevated transaminases, and then the patient is referred to a hepatologist, who figures out what is really going on,” said Dr. Kim.
“This approach is limited, so we need to get SAFE into primary care so these doctors can automatically calculate their scores, and if the patient is over 100 [high risk of chronic liver disease], then they need help [referral to a hepatologist].”
Liver deaths sharply rising
Public health data show that more people are dying of liver disease today than previously. Deaths in the United States have doubled over the past 20 years, said Dr. Kim. “If our mission is to help these patients and prevent death, [things are] moving in the wrong direction.”
He stressed that in order to change the direction, “primary care doctors need to engage with the issue and have appropriate tools to identify people with liver disease.”
Most often, the reason for this rise in deaths is that cases are being diagnosed at advanced stages of disease in which reversibility is limited, he added. “We want to move upstream where people might have early-stage disease and where we can intervene and make a difference.”
In an effort to help earlier detection of liver disease, the SAFE score was developed and validated by Dr. Kim and his colleagues to detect clinically significant (greater than stage 2) fibrosis in patients with NAFLD in primary care. The score is based upon age, body mass index, diabetes, platelet level, aspartate and alanine aminotransferase levels, and globulin level. A score of less than zero signifies that a patient is at low risk for liver fibrosis, while a score greater than 100 signifies a high risk of fibrosis. A score between 0 and 99 denotes intermediate risk of fibrosis.
“Unlike other noninvasive tests that detect advanced fibrosis, this one detects early-stage fibrosis. We’ve shown that the SAFE estimator is better than all other blood-based markers,” explained Dr. Kim.
Applying SAFE to the general population
In the study presented here at EASL, Dr. Kim aimed to expand the horizon for SAFE testing to the U.S. general population and to assess whether SAFE was effective in screening for chronic liver disease regardless of steatosis of the liver.
Together with first author Nakia Chung, MD, also from Stanford University, Dr. Kim applied the SAFE score to data from 7,156 participants of the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. NHANES is representative of the noninstitutionalized, civilian population of the United States. It includes broad demographic, clinical, and laboratory data, including transient elastography data. FibroScans were first used in 2017, so the investigators had 3 years of FibroScan data with which to validate the score.
The researchers extrapolated the NHANES sample data to the U.S. population. They found that the proportion of adults with steatosis (CAP score > 274 dB/m) and significant fibrosis (LSM > 8.0 kPa) was 42.7% (95% confidence interval, 41.0%- 44.3%) and 8.9% (7.6%-10.2%), respectively. In addition, 11.3% (10.2%-12.5%) of the adult U.S. population demonstrated a significant amount of alcohol use, 2.3% (1.4%-3.3%) showed evidence of hepatitis B or C, and 5.4% (4.6%-6.2%) had elevated serum ferritin levels.
The researchers then stratified the patients according to previously defined SAFE tiers of low, intermediate, and high risk and projected findings to the U.S. general population.
“When we applied our score to the general population, we found multiple abnormalities in the high-risk groups [SAFE >100] having Fibroscan data that are consistent with stage 2 or higher fibrosis regardless of etiology, “Dr. Kim pointed out.
Results also showed that very few patients with SAFE less than 0 had liver fibrosis (4% among those with liver stiffness measure [LSM] > 8kPa, and 0.8% with LSM > 12kPa). Among those with SAFE > 100, nearly a third (31.5%) had LSM of > 8kPa, and 16.5% had LSM > 12kPa.
In addition to fibrosis, liver abnormalities were common among patients with SAFE greater than 100, including steatosis (68.0%), viral hepatitis (7.0%), and abnormal ferritin levels (12.9%); 10.8% of these patients used alcohol.
“Right now, some patients are referred, but on examination and FibroScan, they might actually be okay, so it it’s a waste of time and money for everyone. We can preempt all of this by doing a blood test and focusing on those people who really need a scan,” said Dr. Kim.
The researcher is now working with primary care colleagues to help further develop and integrate SAFE into the primary care setting.
Fibrosis score in patients with metabolic dysfunction
Also presenting at the same session on population health was Willem Pieter Brouwer, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. He reported results of a validation study of a new risk score – the Metabolic Dysfunction-Associated Fibrosis–5 (MAF-5) score – for use for people with metabolic dysfunction who are recommended for screening for liver fibrosis.
“We believe the MAF-5 score may be a good alternative to the FIB-4 [a liver fibrosis biomarker] for use in the referral pathway for liver health evaluation,” remarked Dr. Brouwer. “The clinical practice guidelines recommend using FIB-4 scores, but these have a poor-moderate performance in the population setting.
“We developed and validated our score in a population of 5,500 from the NHANES 2017-2020 cycle and validated the score in populations from Rotterdam, which is a cohort of elderly participants, and in fibrosis among patients with biopsy-proven NAFLD from Colombia and Belgium,” he explained.
He also validated the score against different existing scoring systems and different methods of measuring liver stiffness and validated it for prognostic use to predict all-cause mortality in the NHANES III cohort.
Dr. Brouwer removed age as a factor of his new MAF-5 score; the score is thus stable for patients of all ages and is suitable for detecting liver disease in younger patients. “This is very important because these patients are currently underserved and have the most years of life to win.”
Referring to the SAFE score discussed by Dr. Kim, as well as other scores, he said, “The FIB-4, SAFE, and NFS [NAFLD fibrosis score] all include age in the scores, which causes problems and limitations in aging populations, as more and more patients will be referred due to an increasing score. Hence, the elderly are mostly all referred for liver checkups.”
Dr. Kim and Dr. Brouwer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA – An algorithm, the Steatosis-Associated Fibrosis Estimator (SAFE), was developed to detect clinically significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). It is effective at detecting chronic liver disease from all causes with or without NAFLD in the general population, according the results of a U.S. population-based study. The algorithm was designed for use in primary care to help slow the steep rise in liver disease burden.
On the basis of the SAFE score, 61.3% of participants were at low risk for clinically significant fibrosis; 11.2% were at high risk; and 27.5% were at intermediate risk. Upon validation, very few of the low-risk participants had liver fibrosis, while nearly a third of those with a high-risk score had clinically significant fibrosis. In addition, a high percentage of the patients with high-risk SAFE scores had viral hepatitis and elevations in ferritin level.
“This is the first time that there has been a test that provides a score to detect low-risk liver disease in primary care,” said Ray Kim, MD, from Stanford (Calif.) University, senior investigator, who was speaking to this news organization at the annual International Liver Congress sponsored by the European Association for the Study of the Liver
“Primary care doctors currently detect liver disease through a serendipitous abnormal finding on ultrasound or blood tests that detect elevated transaminases, and then the patient is referred to a hepatologist, who figures out what is really going on,” said Dr. Kim.
“This approach is limited, so we need to get SAFE into primary care so these doctors can automatically calculate their scores, and if the patient is over 100 [high risk of chronic liver disease], then they need help [referral to a hepatologist].”
Liver deaths sharply rising
Public health data show that more people are dying of liver disease today than previously. Deaths in the United States have doubled over the past 20 years, said Dr. Kim. “If our mission is to help these patients and prevent death, [things are] moving in the wrong direction.”
He stressed that in order to change the direction, “primary care doctors need to engage with the issue and have appropriate tools to identify people with liver disease.”
Most often, the reason for this rise in deaths is that cases are being diagnosed at advanced stages of disease in which reversibility is limited, he added. “We want to move upstream where people might have early-stage disease and where we can intervene and make a difference.”
In an effort to help earlier detection of liver disease, the SAFE score was developed and validated by Dr. Kim and his colleagues to detect clinically significant (greater than stage 2) fibrosis in patients with NAFLD in primary care. The score is based upon age, body mass index, diabetes, platelet level, aspartate and alanine aminotransferase levels, and globulin level. A score of less than zero signifies that a patient is at low risk for liver fibrosis, while a score greater than 100 signifies a high risk of fibrosis. A score between 0 and 99 denotes intermediate risk of fibrosis.
“Unlike other noninvasive tests that detect advanced fibrosis, this one detects early-stage fibrosis. We’ve shown that the SAFE estimator is better than all other blood-based markers,” explained Dr. Kim.
Applying SAFE to the general population
In the study presented here at EASL, Dr. Kim aimed to expand the horizon for SAFE testing to the U.S. general population and to assess whether SAFE was effective in screening for chronic liver disease regardless of steatosis of the liver.
Together with first author Nakia Chung, MD, also from Stanford University, Dr. Kim applied the SAFE score to data from 7,156 participants of the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. NHANES is representative of the noninstitutionalized, civilian population of the United States. It includes broad demographic, clinical, and laboratory data, including transient elastography data. FibroScans were first used in 2017, so the investigators had 3 years of FibroScan data with which to validate the score.
The researchers extrapolated the NHANES sample data to the U.S. population. They found that the proportion of adults with steatosis (CAP score > 274 dB/m) and significant fibrosis (LSM > 8.0 kPa) was 42.7% (95% confidence interval, 41.0%- 44.3%) and 8.9% (7.6%-10.2%), respectively. In addition, 11.3% (10.2%-12.5%) of the adult U.S. population demonstrated a significant amount of alcohol use, 2.3% (1.4%-3.3%) showed evidence of hepatitis B or C, and 5.4% (4.6%-6.2%) had elevated serum ferritin levels.
The researchers then stratified the patients according to previously defined SAFE tiers of low, intermediate, and high risk and projected findings to the U.S. general population.
“When we applied our score to the general population, we found multiple abnormalities in the high-risk groups [SAFE >100] having Fibroscan data that are consistent with stage 2 or higher fibrosis regardless of etiology, “Dr. Kim pointed out.
Results also showed that very few patients with SAFE less than 0 had liver fibrosis (4% among those with liver stiffness measure [LSM] > 8kPa, and 0.8% with LSM > 12kPa). Among those with SAFE > 100, nearly a third (31.5%) had LSM of > 8kPa, and 16.5% had LSM > 12kPa.
In addition to fibrosis, liver abnormalities were common among patients with SAFE greater than 100, including steatosis (68.0%), viral hepatitis (7.0%), and abnormal ferritin levels (12.9%); 10.8% of these patients used alcohol.
“Right now, some patients are referred, but on examination and FibroScan, they might actually be okay, so it it’s a waste of time and money for everyone. We can preempt all of this by doing a blood test and focusing on those people who really need a scan,” said Dr. Kim.
The researcher is now working with primary care colleagues to help further develop and integrate SAFE into the primary care setting.
Fibrosis score in patients with metabolic dysfunction
Also presenting at the same session on population health was Willem Pieter Brouwer, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. He reported results of a validation study of a new risk score – the Metabolic Dysfunction-Associated Fibrosis–5 (MAF-5) score – for use for people with metabolic dysfunction who are recommended for screening for liver fibrosis.
“We believe the MAF-5 score may be a good alternative to the FIB-4 [a liver fibrosis biomarker] for use in the referral pathway for liver health evaluation,” remarked Dr. Brouwer. “The clinical practice guidelines recommend using FIB-4 scores, but these have a poor-moderate performance in the population setting.
“We developed and validated our score in a population of 5,500 from the NHANES 2017-2020 cycle and validated the score in populations from Rotterdam, which is a cohort of elderly participants, and in fibrosis among patients with biopsy-proven NAFLD from Colombia and Belgium,” he explained.
He also validated the score against different existing scoring systems and different methods of measuring liver stiffness and validated it for prognostic use to predict all-cause mortality in the NHANES III cohort.
Dr. Brouwer removed age as a factor of his new MAF-5 score; the score is thus stable for patients of all ages and is suitable for detecting liver disease in younger patients. “This is very important because these patients are currently underserved and have the most years of life to win.”
Referring to the SAFE score discussed by Dr. Kim, as well as other scores, he said, “The FIB-4, SAFE, and NFS [NAFLD fibrosis score] all include age in the scores, which causes problems and limitations in aging populations, as more and more patients will be referred due to an increasing score. Hence, the elderly are mostly all referred for liver checkups.”
Dr. Kim and Dr. Brouwer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ILC 2023
Surgery, radioactive iodine for hyperthyroidism up survival
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ENDO 2023
Children with type 2 diabetes face dire complications as young adults
SAN DIEGO – , show findings from the TODAY prospective, longitudinal study of 699 U.S. children newly diagnosed with type 2 diabetes.
Arterial stiffness and worsened cardiac function often appear in these children within 2-5 years of diagnosis and seem driven in part by the development of hypertension and worsening hemoglobin A1c levels, said Rachelle G. Gandica, MD, at the annual scientific sessions of the American Diabetes Association.
Indeed, an A1c greater than 6.2% at study entry generally predicts these children will fail treatment and is a red flag, said Dr. Gandica. “I teach fellows this all the time, that if a child’s A1c is above 6.2% they will fail, and you have to watch for that,” she noted.
The results from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed, for example, an overall cardiovascular event rate of 3.7/1,000 patient-years in a population that had just reached an average age of 26 years old, with type 2 diabetes diagnosed for an average of more than 13 years.
During follow-up, there were six cases of congestive heart failure, four myocardial infarctions, four strokes, and three cases of coronary artery disease in the cohort. Hypertension ballooned from a prevalence of 19% at study entry to 68% by the end of follow-up.
Dr. Gandica called these and other findings “sobering details” that document the toll type 2 diabetes takes on children, who averaged 14 years old at the time they entered the study – when their diabetes had been diagnosed for an average of about 8 months – and then underwent an average 12.6 years of follow-up.
Investigators also found:
- After more than 12 years of type 2 diabetes, 49% of the cohort had developed diabetic retinopathy, with 3.5% having macular edema.
- Kidney damage (diabetic nephropathy) affected 8% of the cohort at entry, and then increased to a prevalence of 55% after up to 14 years of follow-up.
- Among the 452 girls who entered the study, 141 (31%) later became pregnant, with a total of 260 pregnancies. A quarter of the pregnancies resulted in preterm deliveries (43% went to term), 25% resulted in miscarriage or fetal demise, with the remaining 8% having elective terminations or unknown outcomes.
- Complications in neonates were common, including hypoglycemia (29%), respiratory disorder (19%), and cardiac issues (10%).
Dire prognosis a reason to aggressively treat these patients
It has become apparent from this and other studies in youth with type 2 diabetes that the difference in outcomes between youth and adults is stark and could indicate that type 2 diabetes in childhood or adolescence likely has a different underlying pathology and natural history, with a more aggressive disease course.
The dire prognosis is therefore a reason to aggressively treat these patients with antidiabetic medications from drug classes with proven cardiovascular disease protection, specifically sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists, said Dr. Gandica, a pediatric endocrinologist at Columbia University Medical Center in New York.
“It’s fair to say we now more aggressively use [these agents] in children,” she said in an interview, and noted the very recent approval, just last week, by the U.S. Food and Drug Administration of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) for children as young as 10 years.
“I look forward to prescribing empagliflozin to children with type 2 diabetes to lower their blood pressure and get additional cardiovascular disease benefits,” Dr. Gandica said.
Other newer type 2 diabetes medications approved for U.S. children in the past few years include the once-weekly injectable GLP-1 agonist exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for children with type 2 diabetes aged 10 and older, in 2021, and the daily injectable GLP-1 agonist liraglutide (Victoza, Novo Nordisk) in 2019.
A1c spike heralds treatment failure: ‘Watch for that’
TODAY enrolled 699 children with type 2 diabetes for an average of 8 months since diagnosis at 16 U.S. sites starting in 2004. The protocol began with a run-in phase of up to 6 months, when participating children came off any preexisting antidiabetes medications and then began a metformin-only regimen to bring A1c below 8.0%. If achieved, patients were eligible to continue to randomization.
Participants were randomized to one of three treatment groups: metformin alone, metformin plus lifestyle interventions, or metformin plus rosiglitazone (Avandia, GSK). The primary endpoint was the incidence of treatment failure, defined as A1c that rose back above 8.0% for at least 6 months or persistent metabolic decompensation during initial follow-up, for an average of just under 4 years.
The results showed that only metformin plus rosiglitazone significantly surpassed metformin alone for preventing treatment failure, reported in 2012 in the New England Journal of Medicine
More recent reports on findings from longer-term follow-up have appeared in several journals, including the cardiovascular disease results, reported in 2021 also in the New England Journal of Medicine.
Another key finding from TODAY is the importance of A1c as a risk marker for impending treatment failure. Study findingsshow that an A1c of 6.2% or higher when children entered the study best predicted loss of glycemic control during follow-up. Also, a rise in A1c of at least 0.5 percentage points was significantly associated with loss of glycemic control within the following 3-6 months.
That’s an important message for clinicians, Dr. Gandica concluded.
TODAY and TODAY2 received no commercial funding. Dr. Gandica has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , show findings from the TODAY prospective, longitudinal study of 699 U.S. children newly diagnosed with type 2 diabetes.
Arterial stiffness and worsened cardiac function often appear in these children within 2-5 years of diagnosis and seem driven in part by the development of hypertension and worsening hemoglobin A1c levels, said Rachelle G. Gandica, MD, at the annual scientific sessions of the American Diabetes Association.
Indeed, an A1c greater than 6.2% at study entry generally predicts these children will fail treatment and is a red flag, said Dr. Gandica. “I teach fellows this all the time, that if a child’s A1c is above 6.2% they will fail, and you have to watch for that,” she noted.
The results from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed, for example, an overall cardiovascular event rate of 3.7/1,000 patient-years in a population that had just reached an average age of 26 years old, with type 2 diabetes diagnosed for an average of more than 13 years.
During follow-up, there were six cases of congestive heart failure, four myocardial infarctions, four strokes, and three cases of coronary artery disease in the cohort. Hypertension ballooned from a prevalence of 19% at study entry to 68% by the end of follow-up.
Dr. Gandica called these and other findings “sobering details” that document the toll type 2 diabetes takes on children, who averaged 14 years old at the time they entered the study – when their diabetes had been diagnosed for an average of about 8 months – and then underwent an average 12.6 years of follow-up.
Investigators also found:
- After more than 12 years of type 2 diabetes, 49% of the cohort had developed diabetic retinopathy, with 3.5% having macular edema.
- Kidney damage (diabetic nephropathy) affected 8% of the cohort at entry, and then increased to a prevalence of 55% after up to 14 years of follow-up.
- Among the 452 girls who entered the study, 141 (31%) later became pregnant, with a total of 260 pregnancies. A quarter of the pregnancies resulted in preterm deliveries (43% went to term), 25% resulted in miscarriage or fetal demise, with the remaining 8% having elective terminations or unknown outcomes.
- Complications in neonates were common, including hypoglycemia (29%), respiratory disorder (19%), and cardiac issues (10%).
Dire prognosis a reason to aggressively treat these patients
It has become apparent from this and other studies in youth with type 2 diabetes that the difference in outcomes between youth and adults is stark and could indicate that type 2 diabetes in childhood or adolescence likely has a different underlying pathology and natural history, with a more aggressive disease course.
The dire prognosis is therefore a reason to aggressively treat these patients with antidiabetic medications from drug classes with proven cardiovascular disease protection, specifically sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists, said Dr. Gandica, a pediatric endocrinologist at Columbia University Medical Center in New York.
“It’s fair to say we now more aggressively use [these agents] in children,” she said in an interview, and noted the very recent approval, just last week, by the U.S. Food and Drug Administration of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) for children as young as 10 years.
“I look forward to prescribing empagliflozin to children with type 2 diabetes to lower their blood pressure and get additional cardiovascular disease benefits,” Dr. Gandica said.
Other newer type 2 diabetes medications approved for U.S. children in the past few years include the once-weekly injectable GLP-1 agonist exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for children with type 2 diabetes aged 10 and older, in 2021, and the daily injectable GLP-1 agonist liraglutide (Victoza, Novo Nordisk) in 2019.
A1c spike heralds treatment failure: ‘Watch for that’
TODAY enrolled 699 children with type 2 diabetes for an average of 8 months since diagnosis at 16 U.S. sites starting in 2004. The protocol began with a run-in phase of up to 6 months, when participating children came off any preexisting antidiabetes medications and then began a metformin-only regimen to bring A1c below 8.0%. If achieved, patients were eligible to continue to randomization.
Participants were randomized to one of three treatment groups: metformin alone, metformin plus lifestyle interventions, or metformin plus rosiglitazone (Avandia, GSK). The primary endpoint was the incidence of treatment failure, defined as A1c that rose back above 8.0% for at least 6 months or persistent metabolic decompensation during initial follow-up, for an average of just under 4 years.
The results showed that only metformin plus rosiglitazone significantly surpassed metformin alone for preventing treatment failure, reported in 2012 in the New England Journal of Medicine
More recent reports on findings from longer-term follow-up have appeared in several journals, including the cardiovascular disease results, reported in 2021 also in the New England Journal of Medicine.
Another key finding from TODAY is the importance of A1c as a risk marker for impending treatment failure. Study findingsshow that an A1c of 6.2% or higher when children entered the study best predicted loss of glycemic control during follow-up. Also, a rise in A1c of at least 0.5 percentage points was significantly associated with loss of glycemic control within the following 3-6 months.
That’s an important message for clinicians, Dr. Gandica concluded.
TODAY and TODAY2 received no commercial funding. Dr. Gandica has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , show findings from the TODAY prospective, longitudinal study of 699 U.S. children newly diagnosed with type 2 diabetes.
Arterial stiffness and worsened cardiac function often appear in these children within 2-5 years of diagnosis and seem driven in part by the development of hypertension and worsening hemoglobin A1c levels, said Rachelle G. Gandica, MD, at the annual scientific sessions of the American Diabetes Association.
Indeed, an A1c greater than 6.2% at study entry generally predicts these children will fail treatment and is a red flag, said Dr. Gandica. “I teach fellows this all the time, that if a child’s A1c is above 6.2% they will fail, and you have to watch for that,” she noted.
The results from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed, for example, an overall cardiovascular event rate of 3.7/1,000 patient-years in a population that had just reached an average age of 26 years old, with type 2 diabetes diagnosed for an average of more than 13 years.
During follow-up, there were six cases of congestive heart failure, four myocardial infarctions, four strokes, and three cases of coronary artery disease in the cohort. Hypertension ballooned from a prevalence of 19% at study entry to 68% by the end of follow-up.
Dr. Gandica called these and other findings “sobering details” that document the toll type 2 diabetes takes on children, who averaged 14 years old at the time they entered the study – when their diabetes had been diagnosed for an average of about 8 months – and then underwent an average 12.6 years of follow-up.
Investigators also found:
- After more than 12 years of type 2 diabetes, 49% of the cohort had developed diabetic retinopathy, with 3.5% having macular edema.
- Kidney damage (diabetic nephropathy) affected 8% of the cohort at entry, and then increased to a prevalence of 55% after up to 14 years of follow-up.
- Among the 452 girls who entered the study, 141 (31%) later became pregnant, with a total of 260 pregnancies. A quarter of the pregnancies resulted in preterm deliveries (43% went to term), 25% resulted in miscarriage or fetal demise, with the remaining 8% having elective terminations or unknown outcomes.
- Complications in neonates were common, including hypoglycemia (29%), respiratory disorder (19%), and cardiac issues (10%).
Dire prognosis a reason to aggressively treat these patients
It has become apparent from this and other studies in youth with type 2 diabetes that the difference in outcomes between youth and adults is stark and could indicate that type 2 diabetes in childhood or adolescence likely has a different underlying pathology and natural history, with a more aggressive disease course.
The dire prognosis is therefore a reason to aggressively treat these patients with antidiabetic medications from drug classes with proven cardiovascular disease protection, specifically sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists, said Dr. Gandica, a pediatric endocrinologist at Columbia University Medical Center in New York.
“It’s fair to say we now more aggressively use [these agents] in children,” she said in an interview, and noted the very recent approval, just last week, by the U.S. Food and Drug Administration of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) for children as young as 10 years.
“I look forward to prescribing empagliflozin to children with type 2 diabetes to lower their blood pressure and get additional cardiovascular disease benefits,” Dr. Gandica said.
Other newer type 2 diabetes medications approved for U.S. children in the past few years include the once-weekly injectable GLP-1 agonist exenatide extended release (Bydureon/Bydureon BCise, AstraZeneca) for children with type 2 diabetes aged 10 and older, in 2021, and the daily injectable GLP-1 agonist liraglutide (Victoza, Novo Nordisk) in 2019.
A1c spike heralds treatment failure: ‘Watch for that’
TODAY enrolled 699 children with type 2 diabetes for an average of 8 months since diagnosis at 16 U.S. sites starting in 2004. The protocol began with a run-in phase of up to 6 months, when participating children came off any preexisting antidiabetes medications and then began a metformin-only regimen to bring A1c below 8.0%. If achieved, patients were eligible to continue to randomization.
Participants were randomized to one of three treatment groups: metformin alone, metformin plus lifestyle interventions, or metformin plus rosiglitazone (Avandia, GSK). The primary endpoint was the incidence of treatment failure, defined as A1c that rose back above 8.0% for at least 6 months or persistent metabolic decompensation during initial follow-up, for an average of just under 4 years.
The results showed that only metformin plus rosiglitazone significantly surpassed metformin alone for preventing treatment failure, reported in 2012 in the New England Journal of Medicine
More recent reports on findings from longer-term follow-up have appeared in several journals, including the cardiovascular disease results, reported in 2021 also in the New England Journal of Medicine.
Another key finding from TODAY is the importance of A1c as a risk marker for impending treatment failure. Study findingsshow that an A1c of 6.2% or higher when children entered the study best predicted loss of glycemic control during follow-up. Also, a rise in A1c of at least 0.5 percentage points was significantly associated with loss of glycemic control within the following 3-6 months.
That’s an important message for clinicians, Dr. Gandica concluded.
TODAY and TODAY2 received no commercial funding. Dr. Gandica has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ADA 2023
Cagrilintide with semaglutide: A way to prevent diabesity?
SAN DIEGO – Coadministration of the long-acting amylin analog cagrilintide plus the glucagonlike peptide–1 (GLP-1) agonist semaglutide, dubbed CagriSema, resulted in significantly greater weight loss, along with improved measures of glucose control, than either agent alone, in a small, short phase 2 trial of patients with type 2 diabetes.
Juan P. Frias, MD, presented the findings at the annual scientific sessions of the American Diabetes Association, which were simultaneously published in The Lancet.
“Overall, in this phase 2 trial with pharmacotherapies in this population. CagriSema also had an acceptable safety profile,” the researchers summarized.
“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 studies,” said Dr. Frias, from Velocity Clinical Research, Los Angeles.
In reply to audience questions, he said he was “pleasantly surprised” with the low gastrointestinal adverse events, which may have been related to the slower dosing titration. He also noted that patients in the study did not receive dietary counseling, unlike in the STEP-2 trial, where weight loss with semaglutide was greater than in this study.
Time in normal blood glucose range in the CagriSema group went from 40% at baseline to 89% at week 32, Chantal Mathieu, MD, PhD, reported during a follow-up presentation that focused on the trial’s CGM findings.
“I was extremely happy that we were allowed to include CGM measurement because it does give you more information, especially in a short-term trial,” said Dr. Mathieu, from the Katholieke Universiteit Leuven (Belgium). The CGM data were collected for 10 days preceding baseline and at weeks 20 and 32.
“At this point in time, it is difficult to make a final determination” about potential future clinical applications, session chair Elisabetta Patorno, MD, DrPH, from Harvard Medical School, Boston, said in an interview. “This was a phase 2 randomized controlled trial, so more patients are needed.
“It’s very interesting what was found with the use of CGM, which makes us think whether they should always be part of [trials] versus the more traditional A1c assessment,” Dr. Patorno added.
‘Synergistic effect for both glycemic control and weight loss’
“CagriSema is the next in a series of gut hormone analogs with the potential to herald a new era in treating obesity and preventing diabesity,” the coexistence of type 2 diabetes and obesity, Caroline M. Apovian, MD, and Marie E. McDonnell, MD, both also from Harvard Medical School, wrote in an accompanying editorial in The Lancet.
Cagrilintide plus semaglutide each “effectively delay gastric emptying, suppress glucagon release, and are involved in the regulation of appetite and satiety in the brain,” they noted.
The results – a substantial difference in effect size between the combination drug and each component alone – show that “there is a synergistic effect for both glycemic control and weight loss.
“The weight loss seen in this phase 2 trial of CagriSema in 32 weeks could predict a phase 3 trial result over 1 year that might surpass that of semaglutide (14.9%) and tirzepatide (20.9%) in a population without type 2 diabetes, and might equal that of bariatric surgery (23.5%-30.4%),” they speculated.
However, it’s still early days, the editorialists cautioned. Study limitations include that it was a small trial and the mean duration of type 2 diabetes at baseline was shorter in the CagriSema group (6.4 years) than in the semaglutide or cagrilintide alone groups (9.2 years and 10.7 years, respectively).
The rate of gastrointestinal adverse events was also higher in the CagriSema group (58%) than in the other two groups (about 33%). However, the adverse events “were all mild or moderate and not severe enough to lead to participant withdrawal,” they noted. “Remarkably, only one participant, from the semaglutide group, withdrew due to adverse events during the 32-week trial across all groups.
“Although bariatric surgery remains the most effective treatment for severe obesity, offering the most robust weight reduction, remission of type 2 diabetes, and reduced cardiovascular mortality,” the study suggests that “combination metabolic hormonal therapy could offer all three of these outcomes in the near future,” Dr. Apovian and Dr. McDonnell wrote.
92 patients randomized to three treatments
In the study, researchers randomized 92 adults with type 2 diabetes and a body mass index of at least 27 kg/m2 taking metformin alone (73%) or metformin plus a sodium-glucose cotransporter 2 inhibitor (27%), at 17 sites in the United States, between August and October 2021.
Patients were a mean age of 58 years and 64% were men. Mean A1c was 8.4% and mean bodyweight was 106 kg (234 lb).
They were randomized 1:1:1 to receive up to maximal once-weekly doses of 2.4 mg semaglutide and 2.4 mg cagrilintide (CagriSema, given in two injector pens), 2.4 mg semaglutide (plus placebo), or 2.4 mg cagrilintide (plus placebo).
Both cagrilintide and semaglutide are manufactured by the Danish company Novo Nordisk. Semaglutide is already approved in the United States for type 2 diabetes, as Ozempic, and as the weight-loss drug Wegovy. Cagrilintide is not yet approved.
Treatment doses were escalated every 4 weeks from 0.25 to 0.5 to 1.0 to 1.7 mg to a maintenance dose of 2.4 mg at 16 weeks. Patients then entered a 16-week maintenance phase followed by a 5-week follow-up period.
Among the key findings, the reduction in A1c at 32 weeks, compared with baseline (primary outcome), was –2.2% with CagriSema, –1.8% with semaglutide, and –0.9% with cagrilintide, but was not significantly greater with CagriSema versus semaglutide (–0.4%; P = .07).
However, in a secondary outcome, there was a significantly greater difference in A1c at 32 weeks with CagriSema versus cagrilintide (–1.3%; P < .0001). Moreover, 89% of patients in the CagriSema group reached an A1c less than 7%.
In other secondary outcomes, there was a significantly greater reduction in body weight at 32 weeks with CagriSema versus cagrilintide or semaglutide, with 71% of patients in the CagriSema group achieving greater than 10% reduction in body weight. Patients in the CagriSema group also had clinically relevant improvements in blood pressure, lipids, and high-sensitivity C-reactive protein.
Adverse events – reported in 68% of patients with CagriSema versus 71% with semaglutide and 80% with cagrilintide – were mostly mild or moderate gastrointestinal events, consistent with those seen in these two drug classes.
At week 32, time in range was 89% with CagriSema versus 76% with semaglutide and 72% with cagrilintide.
“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 agonist and an amylin analog in participants with type 2 diabetes,” the researchers summarize. “These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.”
This trial was sponsored by Novo Nordisk. Dr. Frias, Dr. Mathieu, Dr. Apovian, and Dr. McDonnell reported financial relationships with a number of companies.
A version of this article first appeared on Medscape.com.
SAN DIEGO – Coadministration of the long-acting amylin analog cagrilintide plus the glucagonlike peptide–1 (GLP-1) agonist semaglutide, dubbed CagriSema, resulted in significantly greater weight loss, along with improved measures of glucose control, than either agent alone, in a small, short phase 2 trial of patients with type 2 diabetes.
Juan P. Frias, MD, presented the findings at the annual scientific sessions of the American Diabetes Association, which were simultaneously published in The Lancet.
“Overall, in this phase 2 trial with pharmacotherapies in this population. CagriSema also had an acceptable safety profile,” the researchers summarized.
“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 studies,” said Dr. Frias, from Velocity Clinical Research, Los Angeles.
In reply to audience questions, he said he was “pleasantly surprised” with the low gastrointestinal adverse events, which may have been related to the slower dosing titration. He also noted that patients in the study did not receive dietary counseling, unlike in the STEP-2 trial, where weight loss with semaglutide was greater than in this study.
Time in normal blood glucose range in the CagriSema group went from 40% at baseline to 89% at week 32, Chantal Mathieu, MD, PhD, reported during a follow-up presentation that focused on the trial’s CGM findings.
“I was extremely happy that we were allowed to include CGM measurement because it does give you more information, especially in a short-term trial,” said Dr. Mathieu, from the Katholieke Universiteit Leuven (Belgium). The CGM data were collected for 10 days preceding baseline and at weeks 20 and 32.
“At this point in time, it is difficult to make a final determination” about potential future clinical applications, session chair Elisabetta Patorno, MD, DrPH, from Harvard Medical School, Boston, said in an interview. “This was a phase 2 randomized controlled trial, so more patients are needed.
“It’s very interesting what was found with the use of CGM, which makes us think whether they should always be part of [trials] versus the more traditional A1c assessment,” Dr. Patorno added.
‘Synergistic effect for both glycemic control and weight loss’
“CagriSema is the next in a series of gut hormone analogs with the potential to herald a new era in treating obesity and preventing diabesity,” the coexistence of type 2 diabetes and obesity, Caroline M. Apovian, MD, and Marie E. McDonnell, MD, both also from Harvard Medical School, wrote in an accompanying editorial in The Lancet.
Cagrilintide plus semaglutide each “effectively delay gastric emptying, suppress glucagon release, and are involved in the regulation of appetite and satiety in the brain,” they noted.
The results – a substantial difference in effect size between the combination drug and each component alone – show that “there is a synergistic effect for both glycemic control and weight loss.
“The weight loss seen in this phase 2 trial of CagriSema in 32 weeks could predict a phase 3 trial result over 1 year that might surpass that of semaglutide (14.9%) and tirzepatide (20.9%) in a population without type 2 diabetes, and might equal that of bariatric surgery (23.5%-30.4%),” they speculated.
However, it’s still early days, the editorialists cautioned. Study limitations include that it was a small trial and the mean duration of type 2 diabetes at baseline was shorter in the CagriSema group (6.4 years) than in the semaglutide or cagrilintide alone groups (9.2 years and 10.7 years, respectively).
The rate of gastrointestinal adverse events was also higher in the CagriSema group (58%) than in the other two groups (about 33%). However, the adverse events “were all mild or moderate and not severe enough to lead to participant withdrawal,” they noted. “Remarkably, only one participant, from the semaglutide group, withdrew due to adverse events during the 32-week trial across all groups.
“Although bariatric surgery remains the most effective treatment for severe obesity, offering the most robust weight reduction, remission of type 2 diabetes, and reduced cardiovascular mortality,” the study suggests that “combination metabolic hormonal therapy could offer all three of these outcomes in the near future,” Dr. Apovian and Dr. McDonnell wrote.
92 patients randomized to three treatments
In the study, researchers randomized 92 adults with type 2 diabetes and a body mass index of at least 27 kg/m2 taking metformin alone (73%) or metformin plus a sodium-glucose cotransporter 2 inhibitor (27%), at 17 sites in the United States, between August and October 2021.
Patients were a mean age of 58 years and 64% were men. Mean A1c was 8.4% and mean bodyweight was 106 kg (234 lb).
They were randomized 1:1:1 to receive up to maximal once-weekly doses of 2.4 mg semaglutide and 2.4 mg cagrilintide (CagriSema, given in two injector pens), 2.4 mg semaglutide (plus placebo), or 2.4 mg cagrilintide (plus placebo).
Both cagrilintide and semaglutide are manufactured by the Danish company Novo Nordisk. Semaglutide is already approved in the United States for type 2 diabetes, as Ozempic, and as the weight-loss drug Wegovy. Cagrilintide is not yet approved.
Treatment doses were escalated every 4 weeks from 0.25 to 0.5 to 1.0 to 1.7 mg to a maintenance dose of 2.4 mg at 16 weeks. Patients then entered a 16-week maintenance phase followed by a 5-week follow-up period.
Among the key findings, the reduction in A1c at 32 weeks, compared with baseline (primary outcome), was –2.2% with CagriSema, –1.8% with semaglutide, and –0.9% with cagrilintide, but was not significantly greater with CagriSema versus semaglutide (–0.4%; P = .07).
However, in a secondary outcome, there was a significantly greater difference in A1c at 32 weeks with CagriSema versus cagrilintide (–1.3%; P < .0001). Moreover, 89% of patients in the CagriSema group reached an A1c less than 7%.
In other secondary outcomes, there was a significantly greater reduction in body weight at 32 weeks with CagriSema versus cagrilintide or semaglutide, with 71% of patients in the CagriSema group achieving greater than 10% reduction in body weight. Patients in the CagriSema group also had clinically relevant improvements in blood pressure, lipids, and high-sensitivity C-reactive protein.
Adverse events – reported in 68% of patients with CagriSema versus 71% with semaglutide and 80% with cagrilintide – were mostly mild or moderate gastrointestinal events, consistent with those seen in these two drug classes.
At week 32, time in range was 89% with CagriSema versus 76% with semaglutide and 72% with cagrilintide.
“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 agonist and an amylin analog in participants with type 2 diabetes,” the researchers summarize. “These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.”
This trial was sponsored by Novo Nordisk. Dr. Frias, Dr. Mathieu, Dr. Apovian, and Dr. McDonnell reported financial relationships with a number of companies.
A version of this article first appeared on Medscape.com.
SAN DIEGO – Coadministration of the long-acting amylin analog cagrilintide plus the glucagonlike peptide–1 (GLP-1) agonist semaglutide, dubbed CagriSema, resulted in significantly greater weight loss, along with improved measures of glucose control, than either agent alone, in a small, short phase 2 trial of patients with type 2 diabetes.
Juan P. Frias, MD, presented the findings at the annual scientific sessions of the American Diabetes Association, which were simultaneously published in The Lancet.
“Overall, in this phase 2 trial with pharmacotherapies in this population. CagriSema also had an acceptable safety profile,” the researchers summarized.
“These data support further investigation of CagriSema in people with type 2 diabetes in longer and larger phase 3 studies,” said Dr. Frias, from Velocity Clinical Research, Los Angeles.
In reply to audience questions, he said he was “pleasantly surprised” with the low gastrointestinal adverse events, which may have been related to the slower dosing titration. He also noted that patients in the study did not receive dietary counseling, unlike in the STEP-2 trial, where weight loss with semaglutide was greater than in this study.
Time in normal blood glucose range in the CagriSema group went from 40% at baseline to 89% at week 32, Chantal Mathieu, MD, PhD, reported during a follow-up presentation that focused on the trial’s CGM findings.
“I was extremely happy that we were allowed to include CGM measurement because it does give you more information, especially in a short-term trial,” said Dr. Mathieu, from the Katholieke Universiteit Leuven (Belgium). The CGM data were collected for 10 days preceding baseline and at weeks 20 and 32.
“At this point in time, it is difficult to make a final determination” about potential future clinical applications, session chair Elisabetta Patorno, MD, DrPH, from Harvard Medical School, Boston, said in an interview. “This was a phase 2 randomized controlled trial, so more patients are needed.
“It’s very interesting what was found with the use of CGM, which makes us think whether they should always be part of [trials] versus the more traditional A1c assessment,” Dr. Patorno added.
‘Synergistic effect for both glycemic control and weight loss’
“CagriSema is the next in a series of gut hormone analogs with the potential to herald a new era in treating obesity and preventing diabesity,” the coexistence of type 2 diabetes and obesity, Caroline M. Apovian, MD, and Marie E. McDonnell, MD, both also from Harvard Medical School, wrote in an accompanying editorial in The Lancet.
Cagrilintide plus semaglutide each “effectively delay gastric emptying, suppress glucagon release, and are involved in the regulation of appetite and satiety in the brain,” they noted.
The results – a substantial difference in effect size between the combination drug and each component alone – show that “there is a synergistic effect for both glycemic control and weight loss.
“The weight loss seen in this phase 2 trial of CagriSema in 32 weeks could predict a phase 3 trial result over 1 year that might surpass that of semaglutide (14.9%) and tirzepatide (20.9%) in a population without type 2 diabetes, and might equal that of bariatric surgery (23.5%-30.4%),” they speculated.
However, it’s still early days, the editorialists cautioned. Study limitations include that it was a small trial and the mean duration of type 2 diabetes at baseline was shorter in the CagriSema group (6.4 years) than in the semaglutide or cagrilintide alone groups (9.2 years and 10.7 years, respectively).
The rate of gastrointestinal adverse events was also higher in the CagriSema group (58%) than in the other two groups (about 33%). However, the adverse events “were all mild or moderate and not severe enough to lead to participant withdrawal,” they noted. “Remarkably, only one participant, from the semaglutide group, withdrew due to adverse events during the 32-week trial across all groups.
“Although bariatric surgery remains the most effective treatment for severe obesity, offering the most robust weight reduction, remission of type 2 diabetes, and reduced cardiovascular mortality,” the study suggests that “combination metabolic hormonal therapy could offer all three of these outcomes in the near future,” Dr. Apovian and Dr. McDonnell wrote.
92 patients randomized to three treatments
In the study, researchers randomized 92 adults with type 2 diabetes and a body mass index of at least 27 kg/m2 taking metformin alone (73%) or metformin plus a sodium-glucose cotransporter 2 inhibitor (27%), at 17 sites in the United States, between August and October 2021.
Patients were a mean age of 58 years and 64% were men. Mean A1c was 8.4% and mean bodyweight was 106 kg (234 lb).
They were randomized 1:1:1 to receive up to maximal once-weekly doses of 2.4 mg semaglutide and 2.4 mg cagrilintide (CagriSema, given in two injector pens), 2.4 mg semaglutide (plus placebo), or 2.4 mg cagrilintide (plus placebo).
Both cagrilintide and semaglutide are manufactured by the Danish company Novo Nordisk. Semaglutide is already approved in the United States for type 2 diabetes, as Ozempic, and as the weight-loss drug Wegovy. Cagrilintide is not yet approved.
Treatment doses were escalated every 4 weeks from 0.25 to 0.5 to 1.0 to 1.7 mg to a maintenance dose of 2.4 mg at 16 weeks. Patients then entered a 16-week maintenance phase followed by a 5-week follow-up period.
Among the key findings, the reduction in A1c at 32 weeks, compared with baseline (primary outcome), was –2.2% with CagriSema, –1.8% with semaglutide, and –0.9% with cagrilintide, but was not significantly greater with CagriSema versus semaglutide (–0.4%; P = .07).
However, in a secondary outcome, there was a significantly greater difference in A1c at 32 weeks with CagriSema versus cagrilintide (–1.3%; P < .0001). Moreover, 89% of patients in the CagriSema group reached an A1c less than 7%.
In other secondary outcomes, there was a significantly greater reduction in body weight at 32 weeks with CagriSema versus cagrilintide or semaglutide, with 71% of patients in the CagriSema group achieving greater than 10% reduction in body weight. Patients in the CagriSema group also had clinically relevant improvements in blood pressure, lipids, and high-sensitivity C-reactive protein.
Adverse events – reported in 68% of patients with CagriSema versus 71% with semaglutide and 80% with cagrilintide – were mostly mild or moderate gastrointestinal events, consistent with those seen in these two drug classes.
At week 32, time in range was 89% with CagriSema versus 76% with semaglutide and 72% with cagrilintide.
“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 agonist and an amylin analog in participants with type 2 diabetes,” the researchers summarize. “These data support further investigation of CagriSema in this population in longer and larger phase 3 studies.”
This trial was sponsored by Novo Nordisk. Dr. Frias, Dr. Mathieu, Dr. Apovian, and Dr. McDonnell reported financial relationships with a number of companies.
A version of this article first appeared on Medscape.com.
AT ADA 2023
OASIS and PIONEER PLUS support high-dose oral semaglutide
according to the results of two new phase 3 clinical trials.
The two trials, OASIS in patients with overweight or obesity without diabetes and PIONEER PLUS in patients with inadequately controlled type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in The Lancet.
Filip K. Knop, MD, PhD, University of Copenhagen, presented highlights of the OASIS-1 results, and Vanita R. Aroda, MD, Brigham and Women’s Hospital and Harvard University, Boston, presented key findings of PIONEER PLUS, during a press briefing prior to the ADA session.
OASIS-1 showed that “oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Dr. Knop summarized.
And “the PIONEER PLUS trial showed superior glycemic control and body-weight loss and improvement in cardiometabolic risk factors, with higher doses of once-daily oral semaglutide (25 mg and 50 mg) compared with the currently [highest] approved 14-mg dose,” said Dr. Aroda.
Session chair Marion Pragnell, PhD, vice president of research & science at ADA, said in an interview there is a need for multiple treatment options, as different patients respond differently to individual drugs. The oral dose of semaglutide has to be higher than that approved for subcutaneous injection (as Ozempic or Wegovy) because of bioavailability, but small-molecule research is advancing such that in future lower doses of oral drugs may have the same effect as the current lower subcutaneous doses of the drug.
The oral version of semaglutide (Rybelsus) was approved in the United States for type 2 diabetes in doses of 7 mg or 14 mg per day in 2019; it has not been approved for use in obesity.
Dr. Knop remarked that, in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide and the rest prefer weekly injected semaglutide.
“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” he added.
Participants in OASIS and PIONEER PLUS were instructed to take the once-daily study drug tablet in the morning, in the fasting state, with up to half a glass of water (120 mL) at least 30 minutes before intake of any other food, beverage, or oral medication.
OASIS: 50-mg daily pill in adults with overweight or obesity
OASIS is, to their knowledge, “the first trial to assess the bodyweight-lowering effect of an oral GLP-1 agonist (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” Dr. Knop and colleagues wrote.
The 50-mg dose induced clinically meaningful reductions in bodyweight, with accompanying improvements in cardiometabolic risk factors, consistent with results reported for subcutaneous semaglutide 2.4 mg once weekly (Wegovy) in a similar population.
As an adjunct to diet and physical activity, oral semaglutide 50 mg led to a mean bodyweight reduction of 15.1%, compared with 2.4% in the placebo group, and greater percentages of participants reaching bodyweight reduction targets of at least 5%, 10%, 15%, and 20%.
Body-weight reductions were accompanied by significant improvements in cardiometabolic risk factors, compared with placebo.
“These results indicate that oral semaglutide 50 mg could provide an effective, future option for people with overweight or obesity who would benefit from a GLP-1 receptor agonist,” they concluded.
PIONEER PLUS: Inadequately controlled type 2 diabetes
Reporting the PIONEER PLUS data, Dr. Aroda and colleagues said: “For people with inadequately controlled type 2 diabetes on a stable dose of one to three oral glucose-lowering drugs, higher doses (25 mg and 50 mg) of once-daily oral semaglutide provided more effective glycemic control and greater bodyweight loss than 14 mg semaglutide, without additional safety concerns.”
PIONEER PLUS is the first study to indicate that these bigger doses of semaglutide might provide a highly effective oral option to improve both glycemic control and weight loss in type 2 diabetes.
“This trial provides compelling evidence that the availability of a wider range of doses of oral semaglutide will allow for individualized dosing to the desired effect, and the ability to intensify treatment as needed,” said Dr. Aroda. “We are hopeful that these results encourage earlier effective management of type 2 diabetes and allow for broader management in the primary care setting.”
In an accompanying editorial Christina H. Sherrill, PharmD, and Andrew Y. Hwang, PharmD, write: “This expansion in dosing titration might provide clinicians with more opportunities to obtain the maximum efficacy of this oral GLP-1 agonist.”
But additional investigations “to establish whether the superior glycemic reduction seen at these higher doses translates into cardiovascular risk reduction” are needed, said Dr. Sherrill, of High Point (N.C.) University, and Dr. Hwang, of Massachusetts College of Pharmacy and Health Sciences University, Boston.
Such investigations “would further elucidate the place in therapy of high-dose oral semaglutide,” they concluded.
Dr. Aroda and colleagues agreed: “Future real-world studies will be needed to investigate the clinical impact of the availability of higher doses of oral semaglutide.”
The trials were funded by Novo Nordisk.
A version of this article originally appeared on Medscape.com.
according to the results of two new phase 3 clinical trials.
The two trials, OASIS in patients with overweight or obesity without diabetes and PIONEER PLUS in patients with inadequately controlled type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in The Lancet.
Filip K. Knop, MD, PhD, University of Copenhagen, presented highlights of the OASIS-1 results, and Vanita R. Aroda, MD, Brigham and Women’s Hospital and Harvard University, Boston, presented key findings of PIONEER PLUS, during a press briefing prior to the ADA session.
OASIS-1 showed that “oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Dr. Knop summarized.
And “the PIONEER PLUS trial showed superior glycemic control and body-weight loss and improvement in cardiometabolic risk factors, with higher doses of once-daily oral semaglutide (25 mg and 50 mg) compared with the currently [highest] approved 14-mg dose,” said Dr. Aroda.
Session chair Marion Pragnell, PhD, vice president of research & science at ADA, said in an interview there is a need for multiple treatment options, as different patients respond differently to individual drugs. The oral dose of semaglutide has to be higher than that approved for subcutaneous injection (as Ozempic or Wegovy) because of bioavailability, but small-molecule research is advancing such that in future lower doses of oral drugs may have the same effect as the current lower subcutaneous doses of the drug.
The oral version of semaglutide (Rybelsus) was approved in the United States for type 2 diabetes in doses of 7 mg or 14 mg per day in 2019; it has not been approved for use in obesity.
Dr. Knop remarked that, in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide and the rest prefer weekly injected semaglutide.
“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” he added.
Participants in OASIS and PIONEER PLUS were instructed to take the once-daily study drug tablet in the morning, in the fasting state, with up to half a glass of water (120 mL) at least 30 minutes before intake of any other food, beverage, or oral medication.
OASIS: 50-mg daily pill in adults with overweight or obesity
OASIS is, to their knowledge, “the first trial to assess the bodyweight-lowering effect of an oral GLP-1 agonist (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” Dr. Knop and colleagues wrote.
The 50-mg dose induced clinically meaningful reductions in bodyweight, with accompanying improvements in cardiometabolic risk factors, consistent with results reported for subcutaneous semaglutide 2.4 mg once weekly (Wegovy) in a similar population.
As an adjunct to diet and physical activity, oral semaglutide 50 mg led to a mean bodyweight reduction of 15.1%, compared with 2.4% in the placebo group, and greater percentages of participants reaching bodyweight reduction targets of at least 5%, 10%, 15%, and 20%.
Body-weight reductions were accompanied by significant improvements in cardiometabolic risk factors, compared with placebo.
“These results indicate that oral semaglutide 50 mg could provide an effective, future option for people with overweight or obesity who would benefit from a GLP-1 receptor agonist,” they concluded.
PIONEER PLUS: Inadequately controlled type 2 diabetes
Reporting the PIONEER PLUS data, Dr. Aroda and colleagues said: “For people with inadequately controlled type 2 diabetes on a stable dose of one to three oral glucose-lowering drugs, higher doses (25 mg and 50 mg) of once-daily oral semaglutide provided more effective glycemic control and greater bodyweight loss than 14 mg semaglutide, without additional safety concerns.”
PIONEER PLUS is the first study to indicate that these bigger doses of semaglutide might provide a highly effective oral option to improve both glycemic control and weight loss in type 2 diabetes.
“This trial provides compelling evidence that the availability of a wider range of doses of oral semaglutide will allow for individualized dosing to the desired effect, and the ability to intensify treatment as needed,” said Dr. Aroda. “We are hopeful that these results encourage earlier effective management of type 2 diabetes and allow for broader management in the primary care setting.”
In an accompanying editorial Christina H. Sherrill, PharmD, and Andrew Y. Hwang, PharmD, write: “This expansion in dosing titration might provide clinicians with more opportunities to obtain the maximum efficacy of this oral GLP-1 agonist.”
But additional investigations “to establish whether the superior glycemic reduction seen at these higher doses translates into cardiovascular risk reduction” are needed, said Dr. Sherrill, of High Point (N.C.) University, and Dr. Hwang, of Massachusetts College of Pharmacy and Health Sciences University, Boston.
Such investigations “would further elucidate the place in therapy of high-dose oral semaglutide,” they concluded.
Dr. Aroda and colleagues agreed: “Future real-world studies will be needed to investigate the clinical impact of the availability of higher doses of oral semaglutide.”
The trials were funded by Novo Nordisk.
A version of this article originally appeared on Medscape.com.
according to the results of two new phase 3 clinical trials.
The two trials, OASIS in patients with overweight or obesity without diabetes and PIONEER PLUS in patients with inadequately controlled type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association and simultaneously published in The Lancet.
Filip K. Knop, MD, PhD, University of Copenhagen, presented highlights of the OASIS-1 results, and Vanita R. Aroda, MD, Brigham and Women’s Hospital and Harvard University, Boston, presented key findings of PIONEER PLUS, during a press briefing prior to the ADA session.
OASIS-1 showed that “oral semaglutide 50 mg may represent an effective option for the treatment of obesity, particularly in patients who prefer oral administration,” Dr. Knop summarized.
And “the PIONEER PLUS trial showed superior glycemic control and body-weight loss and improvement in cardiometabolic risk factors, with higher doses of once-daily oral semaglutide (25 mg and 50 mg) compared with the currently [highest] approved 14-mg dose,” said Dr. Aroda.
Session chair Marion Pragnell, PhD, vice president of research & science at ADA, said in an interview there is a need for multiple treatment options, as different patients respond differently to individual drugs. The oral dose of semaglutide has to be higher than that approved for subcutaneous injection (as Ozempic or Wegovy) because of bioavailability, but small-molecule research is advancing such that in future lower doses of oral drugs may have the same effect as the current lower subcutaneous doses of the drug.
The oral version of semaglutide (Rybelsus) was approved in the United States for type 2 diabetes in doses of 7 mg or 14 mg per day in 2019; it has not been approved for use in obesity.
Dr. Knop remarked that, in his clinical practice, about 25% of patients with type 2 diabetes prefer daily oral semaglutide and the rest prefer weekly injected semaglutide.
“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” he added.
Participants in OASIS and PIONEER PLUS were instructed to take the once-daily study drug tablet in the morning, in the fasting state, with up to half a glass of water (120 mL) at least 30 minutes before intake of any other food, beverage, or oral medication.
OASIS: 50-mg daily pill in adults with overweight or obesity
OASIS is, to their knowledge, “the first trial to assess the bodyweight-lowering effect of an oral GLP-1 agonist (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” Dr. Knop and colleagues wrote.
The 50-mg dose induced clinically meaningful reductions in bodyweight, with accompanying improvements in cardiometabolic risk factors, consistent with results reported for subcutaneous semaglutide 2.4 mg once weekly (Wegovy) in a similar population.
As an adjunct to diet and physical activity, oral semaglutide 50 mg led to a mean bodyweight reduction of 15.1%, compared with 2.4% in the placebo group, and greater percentages of participants reaching bodyweight reduction targets of at least 5%, 10%, 15%, and 20%.
Body-weight reductions were accompanied by significant improvements in cardiometabolic risk factors, compared with placebo.
“These results indicate that oral semaglutide 50 mg could provide an effective, future option for people with overweight or obesity who would benefit from a GLP-1 receptor agonist,” they concluded.
PIONEER PLUS: Inadequately controlled type 2 diabetes
Reporting the PIONEER PLUS data, Dr. Aroda and colleagues said: “For people with inadequately controlled type 2 diabetes on a stable dose of one to three oral glucose-lowering drugs, higher doses (25 mg and 50 mg) of once-daily oral semaglutide provided more effective glycemic control and greater bodyweight loss than 14 mg semaglutide, without additional safety concerns.”
PIONEER PLUS is the first study to indicate that these bigger doses of semaglutide might provide a highly effective oral option to improve both glycemic control and weight loss in type 2 diabetes.
“This trial provides compelling evidence that the availability of a wider range of doses of oral semaglutide will allow for individualized dosing to the desired effect, and the ability to intensify treatment as needed,” said Dr. Aroda. “We are hopeful that these results encourage earlier effective management of type 2 diabetes and allow for broader management in the primary care setting.”
In an accompanying editorial Christina H. Sherrill, PharmD, and Andrew Y. Hwang, PharmD, write: “This expansion in dosing titration might provide clinicians with more opportunities to obtain the maximum efficacy of this oral GLP-1 agonist.”
But additional investigations “to establish whether the superior glycemic reduction seen at these higher doses translates into cardiovascular risk reduction” are needed, said Dr. Sherrill, of High Point (N.C.) University, and Dr. Hwang, of Massachusetts College of Pharmacy and Health Sciences University, Boston.
Such investigations “would further elucidate the place in therapy of high-dose oral semaglutide,” they concluded.
Dr. Aroda and colleagues agreed: “Future real-world studies will be needed to investigate the clinical impact of the availability of higher doses of oral semaglutide.”
The trials were funded by Novo Nordisk.
A version of this article originally appeared on Medscape.com.
FROM ADA 2023
Women with atrial fibrillation more likely to develop dementia
New data suggest a significantly stronger link in women compared with men between atrial fibrillation (AF) and mild cognitive impairment (MCI) and dementia.
“Our findings imply that women with AF may be at higher risk for MCI and dementia with potentially more rapid disease progression from normal cognition to MCI or dementia than women without AF or men with and without AF,” wrote authors of a new study led by Kathryn A. Wood, PhD, RN, Neil Hodgson Woodruff School of Nursing at Emory University in Atlanta.
The findings were published online in Alzheimer’s & Dementia.
Researchers used the National Alzheimer’s Coordinating Center data with 43,630 patients and analyzed sex differences between men and women with AF and their performance on neuropsychological tests and cognitive disease progression.
Higher odds of dementia, MCI in women
According to the paper, AF is associated with higher odds of dementia (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.22-7.37) in women and MCI in women (OR, 3.43; 95% CI, 1.55-7.55) compared with men.
Women with AF and normal cognition at baseline had a higher risk of disease progression (hazard ratio [HR], 1.26; 95% CI, 1.06-1.50) from normal to MCI and from MCI to vascular dementia (HR, 3.27; 95% CI, 1.89-5.65) than that of men with AF or men and women without AF.
AF is a major public health problem linked with stroke and heart failure, and is an independent risk factor of increased mortality. It is associated with higher risk of cognitive impairment and dementia independent of stroke history.
Cognitive screening for AF patients
The authors wrote that cognitive screening, especially in women, should be part of yearly cardiology visits for patients with AF to help identify early those at highest risk for cognitive disease.
T. Jared Bunch, MD, professor of medicine in the division of cardiovascular medicine at University of Utah in Salt Lake City, said in an interview, “We have learned that how we treat atrial fibrillation can influence risk.”
First, he said, outcomes, including brain health, are better when rhythm control approaches are used within the first year of diagnosis.
“Restoring a normal heart rhythm improves brain perfusion and cognitive function. Next, aggressive rhythm control – such as catheter ablation – is associated with much lower long-term risks of dementia in the [patients]. Finally, early and effective use of anticoagulation in patients with atrial fibrillation lowers risk of stroke, dementia, and cognitive decline.”
Several factors unknown
Dr. Bunch said there are some unknowns in the study, such as how long patients were in atrial fibrillation.
He said one way to address the inequities is to refer women earlier as women are often referred later in disease to specialty care, which can have consequences.
He said it is not known how many people underwent early and effective rhythm control.
“Women also are less likely to receive catheter ablation, a cardioversion, or be placed on antiarrhythmic drugs,” said Dr. Bunch, who was not part of the study. “These also represent potential opportunities to improve outcomes by treating the rhythm in a similar and aggressive manner in both men and women.”
Also unknown is how many people were on effective oral anticoagulation, Dr. Bunch noted.
The study importantly highlights a significant problem surrounding the care of women with AF, he said, but there are strategies to improve outcomes.
In addition to earlier screening and referral for women, providers should recognize that men and women may present differently with different AF symptoms. He added that physicians should offer catheter ablation, the most effective treatment, equally to men and women who are candidates.
In all people, he said, it’s important “to start anticoagulation very early in the disease to lower the risk of micro- and macrothrombotic events that lead to poor brain health and function.”
The study authors and Dr. Bunch declared no relevant financial relationships.
New data suggest a significantly stronger link in women compared with men between atrial fibrillation (AF) and mild cognitive impairment (MCI) and dementia.
“Our findings imply that women with AF may be at higher risk for MCI and dementia with potentially more rapid disease progression from normal cognition to MCI or dementia than women without AF or men with and without AF,” wrote authors of a new study led by Kathryn A. Wood, PhD, RN, Neil Hodgson Woodruff School of Nursing at Emory University in Atlanta.
The findings were published online in Alzheimer’s & Dementia.
Researchers used the National Alzheimer’s Coordinating Center data with 43,630 patients and analyzed sex differences between men and women with AF and their performance on neuropsychological tests and cognitive disease progression.
Higher odds of dementia, MCI in women
According to the paper, AF is associated with higher odds of dementia (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.22-7.37) in women and MCI in women (OR, 3.43; 95% CI, 1.55-7.55) compared with men.
Women with AF and normal cognition at baseline had a higher risk of disease progression (hazard ratio [HR], 1.26; 95% CI, 1.06-1.50) from normal to MCI and from MCI to vascular dementia (HR, 3.27; 95% CI, 1.89-5.65) than that of men with AF or men and women without AF.
AF is a major public health problem linked with stroke and heart failure, and is an independent risk factor of increased mortality. It is associated with higher risk of cognitive impairment and dementia independent of stroke history.
Cognitive screening for AF patients
The authors wrote that cognitive screening, especially in women, should be part of yearly cardiology visits for patients with AF to help identify early those at highest risk for cognitive disease.
T. Jared Bunch, MD, professor of medicine in the division of cardiovascular medicine at University of Utah in Salt Lake City, said in an interview, “We have learned that how we treat atrial fibrillation can influence risk.”
First, he said, outcomes, including brain health, are better when rhythm control approaches are used within the first year of diagnosis.
“Restoring a normal heart rhythm improves brain perfusion and cognitive function. Next, aggressive rhythm control – such as catheter ablation – is associated with much lower long-term risks of dementia in the [patients]. Finally, early and effective use of anticoagulation in patients with atrial fibrillation lowers risk of stroke, dementia, and cognitive decline.”
Several factors unknown
Dr. Bunch said there are some unknowns in the study, such as how long patients were in atrial fibrillation.
He said one way to address the inequities is to refer women earlier as women are often referred later in disease to specialty care, which can have consequences.
He said it is not known how many people underwent early and effective rhythm control.
“Women also are less likely to receive catheter ablation, a cardioversion, or be placed on antiarrhythmic drugs,” said Dr. Bunch, who was not part of the study. “These also represent potential opportunities to improve outcomes by treating the rhythm in a similar and aggressive manner in both men and women.”
Also unknown is how many people were on effective oral anticoagulation, Dr. Bunch noted.
The study importantly highlights a significant problem surrounding the care of women with AF, he said, but there are strategies to improve outcomes.
In addition to earlier screening and referral for women, providers should recognize that men and women may present differently with different AF symptoms. He added that physicians should offer catheter ablation, the most effective treatment, equally to men and women who are candidates.
In all people, he said, it’s important “to start anticoagulation very early in the disease to lower the risk of micro- and macrothrombotic events that lead to poor brain health and function.”
The study authors and Dr. Bunch declared no relevant financial relationships.
New data suggest a significantly stronger link in women compared with men between atrial fibrillation (AF) and mild cognitive impairment (MCI) and dementia.
“Our findings imply that women with AF may be at higher risk for MCI and dementia with potentially more rapid disease progression from normal cognition to MCI or dementia than women without AF or men with and without AF,” wrote authors of a new study led by Kathryn A. Wood, PhD, RN, Neil Hodgson Woodruff School of Nursing at Emory University in Atlanta.
The findings were published online in Alzheimer’s & Dementia.
Researchers used the National Alzheimer’s Coordinating Center data with 43,630 patients and analyzed sex differences between men and women with AF and their performance on neuropsychological tests and cognitive disease progression.
Higher odds of dementia, MCI in women
According to the paper, AF is associated with higher odds of dementia (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.22-7.37) in women and MCI in women (OR, 3.43; 95% CI, 1.55-7.55) compared with men.
Women with AF and normal cognition at baseline had a higher risk of disease progression (hazard ratio [HR], 1.26; 95% CI, 1.06-1.50) from normal to MCI and from MCI to vascular dementia (HR, 3.27; 95% CI, 1.89-5.65) than that of men with AF or men and women without AF.
AF is a major public health problem linked with stroke and heart failure, and is an independent risk factor of increased mortality. It is associated with higher risk of cognitive impairment and dementia independent of stroke history.
Cognitive screening for AF patients
The authors wrote that cognitive screening, especially in women, should be part of yearly cardiology visits for patients with AF to help identify early those at highest risk for cognitive disease.
T. Jared Bunch, MD, professor of medicine in the division of cardiovascular medicine at University of Utah in Salt Lake City, said in an interview, “We have learned that how we treat atrial fibrillation can influence risk.”
First, he said, outcomes, including brain health, are better when rhythm control approaches are used within the first year of diagnosis.
“Restoring a normal heart rhythm improves brain perfusion and cognitive function. Next, aggressive rhythm control – such as catheter ablation – is associated with much lower long-term risks of dementia in the [patients]. Finally, early and effective use of anticoagulation in patients with atrial fibrillation lowers risk of stroke, dementia, and cognitive decline.”
Several factors unknown
Dr. Bunch said there are some unknowns in the study, such as how long patients were in atrial fibrillation.
He said one way to address the inequities is to refer women earlier as women are often referred later in disease to specialty care, which can have consequences.
He said it is not known how many people underwent early and effective rhythm control.
“Women also are less likely to receive catheter ablation, a cardioversion, or be placed on antiarrhythmic drugs,” said Dr. Bunch, who was not part of the study. “These also represent potential opportunities to improve outcomes by treating the rhythm in a similar and aggressive manner in both men and women.”
Also unknown is how many people were on effective oral anticoagulation, Dr. Bunch noted.
The study importantly highlights a significant problem surrounding the care of women with AF, he said, but there are strategies to improve outcomes.
In addition to earlier screening and referral for women, providers should recognize that men and women may present differently with different AF symptoms. He added that physicians should offer catheter ablation, the most effective treatment, equally to men and women who are candidates.
In all people, he said, it’s important “to start anticoagulation very early in the disease to lower the risk of micro- and macrothrombotic events that lead to poor brain health and function.”
The study authors and Dr. Bunch declared no relevant financial relationships.
FROM ALZHEIMER’S & DEMENTIA
New law allows international medical graduates to bypass U.S. residency
Pediatric nephrologist Bryan Carmody, MD, recalls working alongside an extremely experienced neonatologist during his residency. She had managed a neonatal intensive care unit in her home country of Lithuania, but because she wanted to practice in the United States, it took years of repeat training before she was eligible for a medical license.
“She was very accomplished, and she was wonderful to have as a coresident at the time,” Dr. Carmody said in an interview.
The neonatologist now practices at a U.S. academic medical center, but to obtain that position, she had to complete 3 years of pediatric residency and 3 years of fellowship in the United States, Dr. Carmody said.
Such training for international medical graduates (IMGs) is a routine part of obtaining a U.S. medical license, but
The American Medical Association took similar measures at its recent annual meeting, making it easier for IMGs to gain licensure. Because the pandemic and Russia’s invasion of Ukraine disrupted the process by which some IMGs had their licenses verified, the AMA is now encouraging state licensing boards and other credentialing institutions to accept certification from the Educational Commission for Foreign Medical Graduates as verification, rather than requiring documents directly from international medical schools.
When it comes to Tennessee’s new law, signed by Gov. Bill Lee in April, experienced IMGs who have received medical training abroad can skip U.S. residency requirements and obtain a temporary license to practice medicine in Tennessee if they meet certain qualifications.
The international doctors must demonstrate competency, as determined by the state medical board. In addition, they must have completed a 3-year postgraduate training program in the graduate’s licensing country or otherwise have practiced as a medical professional in which they performed the duties of a physician for at least 3 of the past 5 years outside the United States, according to the new law.
To be approved, IMGs must also have received an employment offer from a Tennessee health care provider that has a residency program accredited by the Accreditation Council for Graduate Medical Education.
If physicians remain in good standing for 2 years, the board will grant them a full and unrestricted license to practice in Tennessee.
“The new legislation opens up a lot of doors for international medical graduates and is also a lifeline for a lot of underserved areas in Tennessee,” said Asim Ansari, MD, a Canadian who attended medical school in the Caribbean and is an advocate for IMGs.
Dr. Ansari is participating in a child and adolescent psychiatry fellowship at the University of Kansas Medical Center, Kansas City, until he can apply for the sixth time to a residency program. “This could possibly be a model that other states may want to implement in a few years.”
What’s behind the law?
A predicted physician shortage in Tennessee drove the legislation, said Rep. Sabi “Doc” Kumar, MD, vice chair for the Tennessee House Health Committee and a cosponsor of the legislation. Legislators hope the law will mitigate that shortage and boost the number of physicians practicing in underserved areas of the state.
“Considering that one in four physicians in the U.S. are international medical gradates, it was important for us to be able to attract those physicians to Tennessee,” he said.
The Tennessee Board of Medical Examiners will develop administrative rules for the law, which may take up to a year, Rep. Kumar said. He expects the program to be available to IMGs beginning in mid-2024.
Upon completion of the program, IMGs will be able to practice general medicine in Tennessee, not a specialty. Requirements for specialty certification would have to be met through the specialties’ respective boards.
Dr. Carmody, who blogs about medical education, including the new legislation, said in an interview the law will greatly benefit experienced IMGs, who often are bypassed as residency candidates because they graduated years ago. Hospitals also win because they can fill positions that otherwise might sit vacant, he said.
Family physician Sahil Bawa, MD, an IMG from India who recently matched into his specialty, said the Tennessee legislation will help fellow IMGs find U.S. medical jobs.
“It’s very difficult for IMGs to get into residency in the U.S.,” he said. “I’ve seen people with medical degrees from other countries drive Uber or do odd jobs to sustain themselves here. I’ve known a few people who have left and gone back to their home country because they were not accepted into a residency.”
Who benefits most?
Dr. Bawa noted that the legislation would not have helped him, as he needed a visa to practice in the United States and the law does not include the sponsoring of visas. The legislation requires IMGs to show evidence of citizenship or evidence that they are legally entitled to live or work in the United States.
U.S. citizen IMGs who haven’t completed residency or who practiced in another country also are left out of the law, Dr. Carmody said.
“This law is designed to take the most accomplished cream of the crop international medical graduates with the most experience and the most sophisticated skill set and send them to Tennessee. I think that’s the intent,” he said. “But many international medical graduates are U.S. citizens who don’t have the opportunity to practice in countries other than United States or do residencies. A lot of these people are sitting on the sidelines, unable to secure residency positions. I’m sure they would be desperate for a program like this.”
Questions remain
“Just because the doctor can get a [temporary] license without the training doesn’t mean employers are going to be interested in sponsoring those doctors,” said Adam Cohen, an immigration attorney who practices in Memphis. “What is the inclination of these employers to hire these physicians who have undergone training outside the U.S.? And will there be skepticism on the part of employers about the competence of these doctors?”
“Hospital systems will be able to hire experienced practitioners for a very low cost,” Dr. Ansari said. “So now you have these additional bodies who can do the work of a physician, but you don’t have to pay them as much as a physician for 2 years. And because some are desperate to work, they will take lower pay as long as they have a pathway to full licensure in Tennessee. What are the protections for these physicians? Who will cover their insurance? Who will be responsible for them, the attendees? And will the attendees be willing to put their license on the line for them?”
In addition, Dr. Carmody questions what, if anything, will encourage IMGs to work in underserved areas in Tennessee after their 2 years are up and whether there will be any incentives to guide them. He wonders, too, whether the physicians will be stuck practicing in Tennessee following completion of the program.
“Will these physicians only be able to work in Tennessee?” he asked. “I think that’s probably going to be the case, because they’ll be licensed in Tennessee, but to go to another state, they would be missing the required residency training. So it might be these folks are stuck in Tennessee unless other states develop reciprocal arrangements.”
Other states would have to decide whether to recognize the Tennessee license acquired through this pathway, Rep. Kumar said.
He explained that the sponsoring sites would be responsible for providing work-hour restrictions and liability protections. There are currently no incentives in the legislation for IMGs to practice in rural, underserved areas, but the hospitals and communities there generally offer incentives when recruiting, Rep. Kumar said.
“The law definitely has the potential to be helpful,” Mr. Cohen said, “because there’s an ability to place providers in the state without having to go through the bottleneck of limited residency slots. If other states see a positive effect on Tennessee or are exploring ways to alleviate their own shortages, it’s possible [they] might follow suit.”
Rep. Kumar agreed that other states will be watching Tennessee to weigh the law’s success.
“I think the law will have to prove itself and show that Tennessee has benefited from it and that the results have been good,” he said. “We are providing a pioneering way for attracting medical graduates and making it easier for them to obtain a license. I would think other states would want to do that.”
A version of this article first appeared on Medscape.com.
Pediatric nephrologist Bryan Carmody, MD, recalls working alongside an extremely experienced neonatologist during his residency. She had managed a neonatal intensive care unit in her home country of Lithuania, but because she wanted to practice in the United States, it took years of repeat training before she was eligible for a medical license.
“She was very accomplished, and she was wonderful to have as a coresident at the time,” Dr. Carmody said in an interview.
The neonatologist now practices at a U.S. academic medical center, but to obtain that position, she had to complete 3 years of pediatric residency and 3 years of fellowship in the United States, Dr. Carmody said.
Such training for international medical graduates (IMGs) is a routine part of obtaining a U.S. medical license, but
The American Medical Association took similar measures at its recent annual meeting, making it easier for IMGs to gain licensure. Because the pandemic and Russia’s invasion of Ukraine disrupted the process by which some IMGs had their licenses verified, the AMA is now encouraging state licensing boards and other credentialing institutions to accept certification from the Educational Commission for Foreign Medical Graduates as verification, rather than requiring documents directly from international medical schools.
When it comes to Tennessee’s new law, signed by Gov. Bill Lee in April, experienced IMGs who have received medical training abroad can skip U.S. residency requirements and obtain a temporary license to practice medicine in Tennessee if they meet certain qualifications.
The international doctors must demonstrate competency, as determined by the state medical board. In addition, they must have completed a 3-year postgraduate training program in the graduate’s licensing country or otherwise have practiced as a medical professional in which they performed the duties of a physician for at least 3 of the past 5 years outside the United States, according to the new law.
To be approved, IMGs must also have received an employment offer from a Tennessee health care provider that has a residency program accredited by the Accreditation Council for Graduate Medical Education.
If physicians remain in good standing for 2 years, the board will grant them a full and unrestricted license to practice in Tennessee.
“The new legislation opens up a lot of doors for international medical graduates and is also a lifeline for a lot of underserved areas in Tennessee,” said Asim Ansari, MD, a Canadian who attended medical school in the Caribbean and is an advocate for IMGs.
Dr. Ansari is participating in a child and adolescent psychiatry fellowship at the University of Kansas Medical Center, Kansas City, until he can apply for the sixth time to a residency program. “This could possibly be a model that other states may want to implement in a few years.”
What’s behind the law?
A predicted physician shortage in Tennessee drove the legislation, said Rep. Sabi “Doc” Kumar, MD, vice chair for the Tennessee House Health Committee and a cosponsor of the legislation. Legislators hope the law will mitigate that shortage and boost the number of physicians practicing in underserved areas of the state.
“Considering that one in four physicians in the U.S. are international medical gradates, it was important for us to be able to attract those physicians to Tennessee,” he said.
The Tennessee Board of Medical Examiners will develop administrative rules for the law, which may take up to a year, Rep. Kumar said. He expects the program to be available to IMGs beginning in mid-2024.
Upon completion of the program, IMGs will be able to practice general medicine in Tennessee, not a specialty. Requirements for specialty certification would have to be met through the specialties’ respective boards.
Dr. Carmody, who blogs about medical education, including the new legislation, said in an interview the law will greatly benefit experienced IMGs, who often are bypassed as residency candidates because they graduated years ago. Hospitals also win because they can fill positions that otherwise might sit vacant, he said.
Family physician Sahil Bawa, MD, an IMG from India who recently matched into his specialty, said the Tennessee legislation will help fellow IMGs find U.S. medical jobs.
“It’s very difficult for IMGs to get into residency in the U.S.,” he said. “I’ve seen people with medical degrees from other countries drive Uber or do odd jobs to sustain themselves here. I’ve known a few people who have left and gone back to their home country because they were not accepted into a residency.”
Who benefits most?
Dr. Bawa noted that the legislation would not have helped him, as he needed a visa to practice in the United States and the law does not include the sponsoring of visas. The legislation requires IMGs to show evidence of citizenship or evidence that they are legally entitled to live or work in the United States.
U.S. citizen IMGs who haven’t completed residency or who practiced in another country also are left out of the law, Dr. Carmody said.
“This law is designed to take the most accomplished cream of the crop international medical graduates with the most experience and the most sophisticated skill set and send them to Tennessee. I think that’s the intent,” he said. “But many international medical graduates are U.S. citizens who don’t have the opportunity to practice in countries other than United States or do residencies. A lot of these people are sitting on the sidelines, unable to secure residency positions. I’m sure they would be desperate for a program like this.”
Questions remain
“Just because the doctor can get a [temporary] license without the training doesn’t mean employers are going to be interested in sponsoring those doctors,” said Adam Cohen, an immigration attorney who practices in Memphis. “What is the inclination of these employers to hire these physicians who have undergone training outside the U.S.? And will there be skepticism on the part of employers about the competence of these doctors?”
“Hospital systems will be able to hire experienced practitioners for a very low cost,” Dr. Ansari said. “So now you have these additional bodies who can do the work of a physician, but you don’t have to pay them as much as a physician for 2 years. And because some are desperate to work, they will take lower pay as long as they have a pathway to full licensure in Tennessee. What are the protections for these physicians? Who will cover their insurance? Who will be responsible for them, the attendees? And will the attendees be willing to put their license on the line for them?”
In addition, Dr. Carmody questions what, if anything, will encourage IMGs to work in underserved areas in Tennessee after their 2 years are up and whether there will be any incentives to guide them. He wonders, too, whether the physicians will be stuck practicing in Tennessee following completion of the program.
“Will these physicians only be able to work in Tennessee?” he asked. “I think that’s probably going to be the case, because they’ll be licensed in Tennessee, but to go to another state, they would be missing the required residency training. So it might be these folks are stuck in Tennessee unless other states develop reciprocal arrangements.”
Other states would have to decide whether to recognize the Tennessee license acquired through this pathway, Rep. Kumar said.
He explained that the sponsoring sites would be responsible for providing work-hour restrictions and liability protections. There are currently no incentives in the legislation for IMGs to practice in rural, underserved areas, but the hospitals and communities there generally offer incentives when recruiting, Rep. Kumar said.
“The law definitely has the potential to be helpful,” Mr. Cohen said, “because there’s an ability to place providers in the state without having to go through the bottleneck of limited residency slots. If other states see a positive effect on Tennessee or are exploring ways to alleviate their own shortages, it’s possible [they] might follow suit.”
Rep. Kumar agreed that other states will be watching Tennessee to weigh the law’s success.
“I think the law will have to prove itself and show that Tennessee has benefited from it and that the results have been good,” he said. “We are providing a pioneering way for attracting medical graduates and making it easier for them to obtain a license. I would think other states would want to do that.”
A version of this article first appeared on Medscape.com.
Pediatric nephrologist Bryan Carmody, MD, recalls working alongside an extremely experienced neonatologist during his residency. She had managed a neonatal intensive care unit in her home country of Lithuania, but because she wanted to practice in the United States, it took years of repeat training before she was eligible for a medical license.
“She was very accomplished, and she was wonderful to have as a coresident at the time,” Dr. Carmody said in an interview.
The neonatologist now practices at a U.S. academic medical center, but to obtain that position, she had to complete 3 years of pediatric residency and 3 years of fellowship in the United States, Dr. Carmody said.
Such training for international medical graduates (IMGs) is a routine part of obtaining a U.S. medical license, but
The American Medical Association took similar measures at its recent annual meeting, making it easier for IMGs to gain licensure. Because the pandemic and Russia’s invasion of Ukraine disrupted the process by which some IMGs had their licenses verified, the AMA is now encouraging state licensing boards and other credentialing institutions to accept certification from the Educational Commission for Foreign Medical Graduates as verification, rather than requiring documents directly from international medical schools.
When it comes to Tennessee’s new law, signed by Gov. Bill Lee in April, experienced IMGs who have received medical training abroad can skip U.S. residency requirements and obtain a temporary license to practice medicine in Tennessee if they meet certain qualifications.
The international doctors must demonstrate competency, as determined by the state medical board. In addition, they must have completed a 3-year postgraduate training program in the graduate’s licensing country or otherwise have practiced as a medical professional in which they performed the duties of a physician for at least 3 of the past 5 years outside the United States, according to the new law.
To be approved, IMGs must also have received an employment offer from a Tennessee health care provider that has a residency program accredited by the Accreditation Council for Graduate Medical Education.
If physicians remain in good standing for 2 years, the board will grant them a full and unrestricted license to practice in Tennessee.
“The new legislation opens up a lot of doors for international medical graduates and is also a lifeline for a lot of underserved areas in Tennessee,” said Asim Ansari, MD, a Canadian who attended medical school in the Caribbean and is an advocate for IMGs.
Dr. Ansari is participating in a child and adolescent psychiatry fellowship at the University of Kansas Medical Center, Kansas City, until he can apply for the sixth time to a residency program. “This could possibly be a model that other states may want to implement in a few years.”
What’s behind the law?
A predicted physician shortage in Tennessee drove the legislation, said Rep. Sabi “Doc” Kumar, MD, vice chair for the Tennessee House Health Committee and a cosponsor of the legislation. Legislators hope the law will mitigate that shortage and boost the number of physicians practicing in underserved areas of the state.
“Considering that one in four physicians in the U.S. are international medical gradates, it was important for us to be able to attract those physicians to Tennessee,” he said.
The Tennessee Board of Medical Examiners will develop administrative rules for the law, which may take up to a year, Rep. Kumar said. He expects the program to be available to IMGs beginning in mid-2024.
Upon completion of the program, IMGs will be able to practice general medicine in Tennessee, not a specialty. Requirements for specialty certification would have to be met through the specialties’ respective boards.
Dr. Carmody, who blogs about medical education, including the new legislation, said in an interview the law will greatly benefit experienced IMGs, who often are bypassed as residency candidates because they graduated years ago. Hospitals also win because they can fill positions that otherwise might sit vacant, he said.
Family physician Sahil Bawa, MD, an IMG from India who recently matched into his specialty, said the Tennessee legislation will help fellow IMGs find U.S. medical jobs.
“It’s very difficult for IMGs to get into residency in the U.S.,” he said. “I’ve seen people with medical degrees from other countries drive Uber or do odd jobs to sustain themselves here. I’ve known a few people who have left and gone back to their home country because they were not accepted into a residency.”
Who benefits most?
Dr. Bawa noted that the legislation would not have helped him, as he needed a visa to practice in the United States and the law does not include the sponsoring of visas. The legislation requires IMGs to show evidence of citizenship or evidence that they are legally entitled to live or work in the United States.
U.S. citizen IMGs who haven’t completed residency or who practiced in another country also are left out of the law, Dr. Carmody said.
“This law is designed to take the most accomplished cream of the crop international medical graduates with the most experience and the most sophisticated skill set and send them to Tennessee. I think that’s the intent,” he said. “But many international medical graduates are U.S. citizens who don’t have the opportunity to practice in countries other than United States or do residencies. A lot of these people are sitting on the sidelines, unable to secure residency positions. I’m sure they would be desperate for a program like this.”
Questions remain
“Just because the doctor can get a [temporary] license without the training doesn’t mean employers are going to be interested in sponsoring those doctors,” said Adam Cohen, an immigration attorney who practices in Memphis. “What is the inclination of these employers to hire these physicians who have undergone training outside the U.S.? And will there be skepticism on the part of employers about the competence of these doctors?”
“Hospital systems will be able to hire experienced practitioners for a very low cost,” Dr. Ansari said. “So now you have these additional bodies who can do the work of a physician, but you don’t have to pay them as much as a physician for 2 years. And because some are desperate to work, they will take lower pay as long as they have a pathway to full licensure in Tennessee. What are the protections for these physicians? Who will cover their insurance? Who will be responsible for them, the attendees? And will the attendees be willing to put their license on the line for them?”
In addition, Dr. Carmody questions what, if anything, will encourage IMGs to work in underserved areas in Tennessee after their 2 years are up and whether there will be any incentives to guide them. He wonders, too, whether the physicians will be stuck practicing in Tennessee following completion of the program.
“Will these physicians only be able to work in Tennessee?” he asked. “I think that’s probably going to be the case, because they’ll be licensed in Tennessee, but to go to another state, they would be missing the required residency training. So it might be these folks are stuck in Tennessee unless other states develop reciprocal arrangements.”
Other states would have to decide whether to recognize the Tennessee license acquired through this pathway, Rep. Kumar said.
He explained that the sponsoring sites would be responsible for providing work-hour restrictions and liability protections. There are currently no incentives in the legislation for IMGs to practice in rural, underserved areas, but the hospitals and communities there generally offer incentives when recruiting, Rep. Kumar said.
“The law definitely has the potential to be helpful,” Mr. Cohen said, “because there’s an ability to place providers in the state without having to go through the bottleneck of limited residency slots. If other states see a positive effect on Tennessee or are exploring ways to alleviate their own shortages, it’s possible [they] might follow suit.”
Rep. Kumar agreed that other states will be watching Tennessee to weigh the law’s success.
“I think the law will have to prove itself and show that Tennessee has benefited from it and that the results have been good,” he said. “We are providing a pioneering way for attracting medical graduates and making it easier for them to obtain a license. I would think other states would want to do that.”
A version of this article first appeared on Medscape.com.