Latest News

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams. 

We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).

When should I start freaking out about a patient’s kidney function? 

Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.

Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.

Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.

If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be. 

Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years. 

Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD. 

We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem. 

Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.

Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well. 

Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.

Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here? 

Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.

Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.

Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable. 

Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes? 

Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.

Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it. 

I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines. 

If you want to hear this fantastic episode and all the great pearls, then click on this link. 

Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams. 

We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).

When should I start freaking out about a patient’s kidney function? 

Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.

Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.

Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.

If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be. 

Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years. 

Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD. 

We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem. 

Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.

Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well. 

Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.

Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here? 

Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.

Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.

Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable. 

Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes? 

Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.

Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it. 

I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines. 

If you want to hear this fantastic episode and all the great pearls, then click on this link. 

Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams. 

We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).

When should I start freaking out about a patient’s kidney function? 

Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.

Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.

Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.

If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be. 

Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years. 

Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD. 

We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem. 

Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.

Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well. 

Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.

Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here? 

Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.

Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.

Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable. 

Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes? 

Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.

Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it. 

I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines. 

If you want to hear this fantastic episode and all the great pearls, then click on this link. 

Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

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

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

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

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

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

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

NEW YORK CITY — The total body skin examination with or without dermatoscopy might eventually be marginalized by noninvasive technologies that greatly reduce the need for biopsy while increasing sensitivity and specificity, according to an expert describing four such technologies now in routine use at his own institution.

For skin cancer screening, existing and coming technologies represent “the future of dermatology,” but “we can and should be [already] trying to incorporate these into routine practice,” said Jonathan Ungar, MD, assistant professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York City.

 

Technologies such as electrical impedance spectroscopy (EIS), optical coherence tomography (OCT), and reflectance confocal microscopy (RCM) have immediate utility for improving skin cancer detection with fewer biopsies, but this is just the beginning, according to Ungar, who is also medical director of the Kimberly and Eric J. Waldman Melanoma and Skin Cancer Center at Mount Sinai, New York City.

“There is going to be a day when we are not cutting to make a diagnosis,” he said during a presentation at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024.

 

Four Noninvasive Tools Are in Routine Use

Each of these technologies, along with total body photography (TBP), is currently in use at Mount Sinai as well as other tertiary centers to improve diagnostic accuracy at the same time they reduce invasive tests. The initial excitement about these technologies was based on their potential to avoid biopsy in cosmetically sensitive areas, but Ungar suggested that wider application is being driven by better rates of detection, less morbidity, and improved patient satisfaction.

Patients are happy to avoid invasive procedures whenever they can, Ungar noted. In addition to concern about pain or discomfort and a small but measurable risk for infection, patients face a wound that requires healing and the potential for an enduring scar whether the histology is positive for a malignancy.

While none of the four technologies Ungar outlined typically provide a yes or no answer regarding the presence of a malignancy, they do improve diagnostic accuracy with a lower rate of biopsy.

 

Each Noninvasive Tool Reduces Biopsy Rates

In the case of EIS, for example, the impedance of a painless and harmless electrical current directed into the skin with a handheld probe differentiates normal from abnormal skin through an EIS algorithm. Ungar said it does not require training. A result negative for an abnormality has about a 90% predictive value, and it means that a biopsy can be avoided if there are no other reasons for suspicion.

With a price estimated in the thousands of dollars, the device and software are “not so expensive,” particularly when the tool results in fewer biopsies, Ungar noted.

OCT has a similar profile. Again, used as an adjunct to other types of evaluations, including a history and visual inspection, this helps in modulating suspicion of malignancy. In published studies, OCT has proven superior to dermatoscopy for cancer detection. Citing a 14-study meta-analysis, Ungar said that the sensitivity of OCT for melanoma exceeds, and the specificity approaches, 90%. For basal cell cancers, it is even better.

RCM involves directing a laser into the skin to detect abnormal cells that reflect light. It enables visualization of the skin by layers to the papillary dermis in a detail that is comparable with histology, according to Ungar. Imaging performed with the device used at Mount Sinai (VivaScope 1500, Caliber Imaging & Diagnostics) is reimbursed by Medicare.

Once comfortable with the technology, scanning and interpretation take slightly more time than that required of EIS or OCT, but, like the others, it is painless and helpful for determining whether further evaluation is needed, according to Ungar.

“It is extremely useful in reducing the number of biopsies,” whether melanoma or basal cell malignancies, he said.

 

Total Body Photograph Helps With Serial Screens

While not specifically a diagnostic tool, TBP can also play a role in reducing biopsies through its highly efficient ability to document the evolution of lesions over time.

As its name implies, essentially the entire body surface is captured by multiple cameras mounted in a circle around the patient. Unlike sequential photos that require far more time to take and store and are challenging to organize and retrieve, the device used at Mount Sinai (Vectra Wb180 1360, Canfield Scientific) can complete the photos in about 2 minutes.

Software for organizing and storing the photos, to which dermatoscope images of individual lesions can be attached if helpful, results in efficient retrieval of photos at sequential visits for evaluating change in any specific lesion.

“It is very easy to use,” according to Ungar, who noted that although the underlying idea is not, the technology of taking, storing, and retrieving photographs has been “perhaps perfected” with this approach.

 

Noninvasive Screening Training Is Appropriate

Year after year, dermatology residents undergo intensive instruction to master the traditional methods of skin examination with the naked eye and the help of a dermatoscope, but Ungar considers the noninvasive tools to be another step forward. They lower miss rates while reducing the need for histopathology.

Adding these new technologies to routine patient care resonates for many experts, even if the protocols of when to use with the tool are not well established.

Angela J. Lamb, MD, an associate professor of dermatology at Mount Sinai, who has been following the work of Ungar with interest, sees merit in his argument. Not surprisingly, she thinks that any approach shown to boost skin cancer detection is something that deserves attention, but she thinks the effort to safely eliminate biopsies with a low likelihood of a positive finding cannot be ignored.

“Patients want to avoid biopsies when they can,” Lamb told this news organization, and she does not think this is limited to biopsies on the face or other cosmetically sensitive areas.

As a result, she said that she does see the rationale for incorporating the newer technologies into routine care and called this an “important” effort to improve the patient experience as well as reduce missed lesions.

Ungar reported financial relationships with AbbVie, Bristol-Myers Squibb, Castle Biosciences, Dermavant, Janssen Pharmaceuticals, Menlo Therapeutics, Mitsubishi Tanabe Pharma America, and UCB. Lamb reported no potential conflicts of interest.

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

NEW YORK CITY — The total body skin examination with or without dermatoscopy might eventually be marginalized by noninvasive technologies that greatly reduce the need for biopsy while increasing sensitivity and specificity, according to an expert describing four such technologies now in routine use at his own institution.

For skin cancer screening, existing and coming technologies represent “the future of dermatology,” but “we can and should be [already] trying to incorporate these into routine practice,” said Jonathan Ungar, MD, assistant professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York City.

 

Technologies such as electrical impedance spectroscopy (EIS), optical coherence tomography (OCT), and reflectance confocal microscopy (RCM) have immediate utility for improving skin cancer detection with fewer biopsies, but this is just the beginning, according to Ungar, who is also medical director of the Kimberly and Eric J. Waldman Melanoma and Skin Cancer Center at Mount Sinai, New York City.

“There is going to be a day when we are not cutting to make a diagnosis,” he said during a presentation at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024.

 

Four Noninvasive Tools Are in Routine Use

Each of these technologies, along with total body photography (TBP), is currently in use at Mount Sinai as well as other tertiary centers to improve diagnostic accuracy at the same time they reduce invasive tests. The initial excitement about these technologies was based on their potential to avoid biopsy in cosmetically sensitive areas, but Ungar suggested that wider application is being driven by better rates of detection, less morbidity, and improved patient satisfaction.

Patients are happy to avoid invasive procedures whenever they can, Ungar noted. In addition to concern about pain or discomfort and a small but measurable risk for infection, patients face a wound that requires healing and the potential for an enduring scar whether the histology is positive for a malignancy.

While none of the four technologies Ungar outlined typically provide a yes or no answer regarding the presence of a malignancy, they do improve diagnostic accuracy with a lower rate of biopsy.

 

Each Noninvasive Tool Reduces Biopsy Rates

In the case of EIS, for example, the impedance of a painless and harmless electrical current directed into the skin with a handheld probe differentiates normal from abnormal skin through an EIS algorithm. Ungar said it does not require training. A result negative for an abnormality has about a 90% predictive value, and it means that a biopsy can be avoided if there are no other reasons for suspicion.

With a price estimated in the thousands of dollars, the device and software are “not so expensive,” particularly when the tool results in fewer biopsies, Ungar noted.

OCT has a similar profile. Again, used as an adjunct to other types of evaluations, including a history and visual inspection, this helps in modulating suspicion of malignancy. In published studies, OCT has proven superior to dermatoscopy for cancer detection. Citing a 14-study meta-analysis, Ungar said that the sensitivity of OCT for melanoma exceeds, and the specificity approaches, 90%. For basal cell cancers, it is even better.

RCM involves directing a laser into the skin to detect abnormal cells that reflect light. It enables visualization of the skin by layers to the papillary dermis in a detail that is comparable with histology, according to Ungar. Imaging performed with the device used at Mount Sinai (VivaScope 1500, Caliber Imaging & Diagnostics) is reimbursed by Medicare.

Once comfortable with the technology, scanning and interpretation take slightly more time than that required of EIS or OCT, but, like the others, it is painless and helpful for determining whether further evaluation is needed, according to Ungar.

“It is extremely useful in reducing the number of biopsies,” whether melanoma or basal cell malignancies, he said.

 

Total Body Photograph Helps With Serial Screens

While not specifically a diagnostic tool, TBP can also play a role in reducing biopsies through its highly efficient ability to document the evolution of lesions over time.

As its name implies, essentially the entire body surface is captured by multiple cameras mounted in a circle around the patient. Unlike sequential photos that require far more time to take and store and are challenging to organize and retrieve, the device used at Mount Sinai (Vectra Wb180 1360, Canfield Scientific) can complete the photos in about 2 minutes.

Software for organizing and storing the photos, to which dermatoscope images of individual lesions can be attached if helpful, results in efficient retrieval of photos at sequential visits for evaluating change in any specific lesion.

“It is very easy to use,” according to Ungar, who noted that although the underlying idea is not, the technology of taking, storing, and retrieving photographs has been “perhaps perfected” with this approach.

 

Noninvasive Screening Training Is Appropriate

Year after year, dermatology residents undergo intensive instruction to master the traditional methods of skin examination with the naked eye and the help of a dermatoscope, but Ungar considers the noninvasive tools to be another step forward. They lower miss rates while reducing the need for histopathology.

Adding these new technologies to routine patient care resonates for many experts, even if the protocols of when to use with the tool are not well established.

Angela J. Lamb, MD, an associate professor of dermatology at Mount Sinai, who has been following the work of Ungar with interest, sees merit in his argument. Not surprisingly, she thinks that any approach shown to boost skin cancer detection is something that deserves attention, but she thinks the effort to safely eliminate biopsies with a low likelihood of a positive finding cannot be ignored.

“Patients want to avoid biopsies when they can,” Lamb told this news organization, and she does not think this is limited to biopsies on the face or other cosmetically sensitive areas.

As a result, she said that she does see the rationale for incorporating the newer technologies into routine care and called this an “important” effort to improve the patient experience as well as reduce missed lesions.

Ungar reported financial relationships with AbbVie, Bristol-Myers Squibb, Castle Biosciences, Dermavant, Janssen Pharmaceuticals, Menlo Therapeutics, Mitsubishi Tanabe Pharma America, and UCB. Lamb reported no potential conflicts of interest.

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

NEW YORK CITY — The total body skin examination with or without dermatoscopy might eventually be marginalized by noninvasive technologies that greatly reduce the need for biopsy while increasing sensitivity and specificity, according to an expert describing four such technologies now in routine use at his own institution.

For skin cancer screening, existing and coming technologies represent “the future of dermatology,” but “we can and should be [already] trying to incorporate these into routine practice,” said Jonathan Ungar, MD, assistant professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York City.

 

Technologies such as electrical impedance spectroscopy (EIS), optical coherence tomography (OCT), and reflectance confocal microscopy (RCM) have immediate utility for improving skin cancer detection with fewer biopsies, but this is just the beginning, according to Ungar, who is also medical director of the Kimberly and Eric J. Waldman Melanoma and Skin Cancer Center at Mount Sinai, New York City.

“There is going to be a day when we are not cutting to make a diagnosis,” he said during a presentation at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024.

 

Four Noninvasive Tools Are in Routine Use

Each of these technologies, along with total body photography (TBP), is currently in use at Mount Sinai as well as other tertiary centers to improve diagnostic accuracy at the same time they reduce invasive tests. The initial excitement about these technologies was based on their potential to avoid biopsy in cosmetically sensitive areas, but Ungar suggested that wider application is being driven by better rates of detection, less morbidity, and improved patient satisfaction.

Patients are happy to avoid invasive procedures whenever they can, Ungar noted. In addition to concern about pain or discomfort and a small but measurable risk for infection, patients face a wound that requires healing and the potential for an enduring scar whether the histology is positive for a malignancy.

While none of the four technologies Ungar outlined typically provide a yes or no answer regarding the presence of a malignancy, they do improve diagnostic accuracy with a lower rate of biopsy.

 

Each Noninvasive Tool Reduces Biopsy Rates

In the case of EIS, for example, the impedance of a painless and harmless electrical current directed into the skin with a handheld probe differentiates normal from abnormal skin through an EIS algorithm. Ungar said it does not require training. A result negative for an abnormality has about a 90% predictive value, and it means that a biopsy can be avoided if there are no other reasons for suspicion.

With a price estimated in the thousands of dollars, the device and software are “not so expensive,” particularly when the tool results in fewer biopsies, Ungar noted.

OCT has a similar profile. Again, used as an adjunct to other types of evaluations, including a history and visual inspection, this helps in modulating suspicion of malignancy. In published studies, OCT has proven superior to dermatoscopy for cancer detection. Citing a 14-study meta-analysis, Ungar said that the sensitivity of OCT for melanoma exceeds, and the specificity approaches, 90%. For basal cell cancers, it is even better.

RCM involves directing a laser into the skin to detect abnormal cells that reflect light. It enables visualization of the skin by layers to the papillary dermis in a detail that is comparable with histology, according to Ungar. Imaging performed with the device used at Mount Sinai (VivaScope 1500, Caliber Imaging & Diagnostics) is reimbursed by Medicare.

Once comfortable with the technology, scanning and interpretation take slightly more time than that required of EIS or OCT, but, like the others, it is painless and helpful for determining whether further evaluation is needed, according to Ungar.

“It is extremely useful in reducing the number of biopsies,” whether melanoma or basal cell malignancies, he said.

 

Total Body Photograph Helps With Serial Screens

While not specifically a diagnostic tool, TBP can also play a role in reducing biopsies through its highly efficient ability to document the evolution of lesions over time.

As its name implies, essentially the entire body surface is captured by multiple cameras mounted in a circle around the patient. Unlike sequential photos that require far more time to take and store and are challenging to organize and retrieve, the device used at Mount Sinai (Vectra Wb180 1360, Canfield Scientific) can complete the photos in about 2 minutes.

Software for organizing and storing the photos, to which dermatoscope images of individual lesions can be attached if helpful, results in efficient retrieval of photos at sequential visits for evaluating change in any specific lesion.

“It is very easy to use,” according to Ungar, who noted that although the underlying idea is not, the technology of taking, storing, and retrieving photographs has been “perhaps perfected” with this approach.

 

Noninvasive Screening Training Is Appropriate

Year after year, dermatology residents undergo intensive instruction to master the traditional methods of skin examination with the naked eye and the help of a dermatoscope, but Ungar considers the noninvasive tools to be another step forward. They lower miss rates while reducing the need for histopathology.

Adding these new technologies to routine patient care resonates for many experts, even if the protocols of when to use with the tool are not well established.

Angela J. Lamb, MD, an associate professor of dermatology at Mount Sinai, who has been following the work of Ungar with interest, sees merit in his argument. Not surprisingly, she thinks that any approach shown to boost skin cancer detection is something that deserves attention, but she thinks the effort to safely eliminate biopsies with a low likelihood of a positive finding cannot be ignored.

“Patients want to avoid biopsies when they can,” Lamb told this news organization, and she does not think this is limited to biopsies on the face or other cosmetically sensitive areas.

As a result, she said that she does see the rationale for incorporating the newer technologies into routine care and called this an “important” effort to improve the patient experience as well as reduce missed lesions.

Ungar reported financial relationships with AbbVie, Bristol-Myers Squibb, Castle Biosciences, Dermavant, Janssen Pharmaceuticals, Menlo Therapeutics, Mitsubishi Tanabe Pharma America, and UCB. Lamb reported no potential conflicts of interest.

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

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The first study funded by the US Department of Veterans Affairs (VA) for psychedelic-assisted therapy since the 1960s is currently enrolling veterans. Researchers are set to evaluate the potential of methylenedioxymethamphetamine (MDMA) for veterans with posttraumatic stress disorder (PTSD) and alcohol use disorder.   
 

The grant—about $1.5 million over 5 years—will fund a randomized, placebo-controlled trial at the Providence VA Medical Center in Rhode Island and the West Haven VA Medical Center in Connecticut by VA researchers affiliated with Brown University and Yale University. Pharmaceutical-grade MDMA will be used, and some participants will be randomly selected to receive an active placebo (lower dose of MDMA). MDMA is a psychedelic compound believed to increase emotional openness, reduce fear, and promote introspection during therapy. 
 

The study is part of the VA’s broader effort to gather definitive scientific evidence on the potential efficacy and safety of psychedelic compounds used in conjunction with psychotherapy to treat PTSD, depression, and related mental health conditions. Veterans service organizations like the American Legion and Disabled American Veterans in addition to mental health clinician groups have also called for expanded research into psychedelic compounds. The National Defense Authorization Act for fiscal year 2024 also authorized the US Department of Defense to perform research on psychedelics within military populations. 
 

In September 2023, VA and other federal clinicians, scientists, and policy makers assessed the state of scientific evidence regarding psychedelic-assisted therapies. The working groups provided advice to VA leadership, including the recommendation for the VA to begin funding its own research into these areas of care.  
 

The guidance was based on previously published studies that have found encouraging results but included few or no veteran participants. For example, a confirmatory phase 3 study by the MAPP2 Study Collaborator Group involved 104 patients, of whom only 16 were veterans.  
 

However, the findings of that study underscored the potential of the treatment: MDMA significantly improved PTSD symptoms and functional impairment, compared with placebo with therapy over 18 weeks. Notably, 45 of 52 (86%) participants treated with MDMA achieved a clinically meaningful benefit, and 37 of 52 (71%) participants no longer met criteria for PTSD by the end of the study. Consistent with an earlier study, no new major safety issues were reported. Common treatment-emergent adverse effects were like those of previous research and consistent with expected effects of MDMA. MDMA did not appear to increase the risk of suicidal ideation, and no suicidal behavior was observed. 
 

The VA researchers has conducted a limited number of small studies on psychedelics in VA facilities using non-VA funding. “VA is on the cutting edge of clinical research for veteran health, including in the investigation of psychedelics for mental health,” said Under Secretary for Health Shereef Elnahal, MD.  
 

The FDA granted breakthrough therapy status for MDMA in the treatment of PTSD and psilocybin for the treatment of depression in 2017 and 2018, respectively, based on promising preliminary research evidence. However, in June 2024 an FDA panel voted against approving a MDMA therapy for PTSD, citing concerns about research practices, a lack of diversity in the trials, and a failure to provide data on adverse effects such as potential for abuse.  
 

In August, the FDA formally rejected the treatment and called for another phase 3 study. “The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape—and the result is people will keep dying.” 
 

Meanwhile, VA Press Secretary Terrence Hayes said in a statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans … VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”

The first study funded by the US Department of Veterans Affairs (VA) for psychedelic-assisted therapy since the 1960s is currently enrolling veterans. Researchers are set to evaluate the potential of methylenedioxymethamphetamine (MDMA) for veterans with posttraumatic stress disorder (PTSD) and alcohol use disorder.   
 

The grant—about $1.5 million over 5 years—will fund a randomized, placebo-controlled trial at the Providence VA Medical Center in Rhode Island and the West Haven VA Medical Center in Connecticut by VA researchers affiliated with Brown University and Yale University. Pharmaceutical-grade MDMA will be used, and some participants will be randomly selected to receive an active placebo (lower dose of MDMA). MDMA is a psychedelic compound believed to increase emotional openness, reduce fear, and promote introspection during therapy. 
 

The study is part of the VA’s broader effort to gather definitive scientific evidence on the potential efficacy and safety of psychedelic compounds used in conjunction with psychotherapy to treat PTSD, depression, and related mental health conditions. Veterans service organizations like the American Legion and Disabled American Veterans in addition to mental health clinician groups have also called for expanded research into psychedelic compounds. The National Defense Authorization Act for fiscal year 2024 also authorized the US Department of Defense to perform research on psychedelics within military populations. 
 

In September 2023, VA and other federal clinicians, scientists, and policy makers assessed the state of scientific evidence regarding psychedelic-assisted therapies. The working groups provided advice to VA leadership, including the recommendation for the VA to begin funding its own research into these areas of care.  
 

The guidance was based on previously published studies that have found encouraging results but included few or no veteran participants. For example, a confirmatory phase 3 study by the MAPP2 Study Collaborator Group involved 104 patients, of whom only 16 were veterans.  
 

However, the findings of that study underscored the potential of the treatment: MDMA significantly improved PTSD symptoms and functional impairment, compared with placebo with therapy over 18 weeks. Notably, 45 of 52 (86%) participants treated with MDMA achieved a clinically meaningful benefit, and 37 of 52 (71%) participants no longer met criteria for PTSD by the end of the study. Consistent with an earlier study, no new major safety issues were reported. Common treatment-emergent adverse effects were like those of previous research and consistent with expected effects of MDMA. MDMA did not appear to increase the risk of suicidal ideation, and no suicidal behavior was observed. 
 

The VA researchers has conducted a limited number of small studies on psychedelics in VA facilities using non-VA funding. “VA is on the cutting edge of clinical research for veteran health, including in the investigation of psychedelics for mental health,” said Under Secretary for Health Shereef Elnahal, MD.  
 

The FDA granted breakthrough therapy status for MDMA in the treatment of PTSD and psilocybin for the treatment of depression in 2017 and 2018, respectively, based on promising preliminary research evidence. However, in June 2024 an FDA panel voted against approving a MDMA therapy for PTSD, citing concerns about research practices, a lack of diversity in the trials, and a failure to provide data on adverse effects such as potential for abuse.  
 

In August, the FDA formally rejected the treatment and called for another phase 3 study. “The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape—and the result is people will keep dying.” 
 

Meanwhile, VA Press Secretary Terrence Hayes said in a statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans … VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”

The first study funded by the US Department of Veterans Affairs (VA) for psychedelic-assisted therapy since the 1960s is currently enrolling veterans. Researchers are set to evaluate the potential of methylenedioxymethamphetamine (MDMA) for veterans with posttraumatic stress disorder (PTSD) and alcohol use disorder.   
 

The grant—about $1.5 million over 5 years—will fund a randomized, placebo-controlled trial at the Providence VA Medical Center in Rhode Island and the West Haven VA Medical Center in Connecticut by VA researchers affiliated with Brown University and Yale University. Pharmaceutical-grade MDMA will be used, and some participants will be randomly selected to receive an active placebo (lower dose of MDMA). MDMA is a psychedelic compound believed to increase emotional openness, reduce fear, and promote introspection during therapy. 
 

The study is part of the VA’s broader effort to gather definitive scientific evidence on the potential efficacy and safety of psychedelic compounds used in conjunction with psychotherapy to treat PTSD, depression, and related mental health conditions. Veterans service organizations like the American Legion and Disabled American Veterans in addition to mental health clinician groups have also called for expanded research into psychedelic compounds. The National Defense Authorization Act for fiscal year 2024 also authorized the US Department of Defense to perform research on psychedelics within military populations. 
 

In September 2023, VA and other federal clinicians, scientists, and policy makers assessed the state of scientific evidence regarding psychedelic-assisted therapies. The working groups provided advice to VA leadership, including the recommendation for the VA to begin funding its own research into these areas of care.  
 

The guidance was based on previously published studies that have found encouraging results but included few or no veteran participants. For example, a confirmatory phase 3 study by the MAPP2 Study Collaborator Group involved 104 patients, of whom only 16 were veterans.  
 

However, the findings of that study underscored the potential of the treatment: MDMA significantly improved PTSD symptoms and functional impairment, compared with placebo with therapy over 18 weeks. Notably, 45 of 52 (86%) participants treated with MDMA achieved a clinically meaningful benefit, and 37 of 52 (71%) participants no longer met criteria for PTSD by the end of the study. Consistent with an earlier study, no new major safety issues were reported. Common treatment-emergent adverse effects were like those of previous research and consistent with expected effects of MDMA. MDMA did not appear to increase the risk of suicidal ideation, and no suicidal behavior was observed. 
 

The VA researchers has conducted a limited number of small studies on psychedelics in VA facilities using non-VA funding. “VA is on the cutting edge of clinical research for veteran health, including in the investigation of psychedelics for mental health,” said Under Secretary for Health Shereef Elnahal, MD.  
 

The FDA granted breakthrough therapy status for MDMA in the treatment of PTSD and psilocybin for the treatment of depression in 2017 and 2018, respectively, based on promising preliminary research evidence. However, in June 2024 an FDA panel voted against approving a MDMA therapy for PTSD, citing concerns about research practices, a lack of diversity in the trials, and a failure to provide data on adverse effects such as potential for abuse.  
 

In August, the FDA formally rejected the treatment and called for another phase 3 study. “The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape—and the result is people will keep dying.” 
 

Meanwhile, VA Press Secretary Terrence Hayes said in a statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans … VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”