Conference Coverage

There is an increased incidence of locally staged Merkel cell carcinoma (MCC) among patients who live in rural areas of the United States, compared with those in urban and metropolitan areas, yet overall survival is worse in rural areas.

This paradox was discovered in an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program that primary author Bryan T. Carroll, MD, PhD, and colleagues presented during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

“MCC is a rare and aggressive neoplasm of the skin with high mortality,” said coauthor Emma Larson, MD, a dermatology clinical research fellow at University Hospitals of Cleveland. “Previous studies have demonstrated that MCC survival is lower in low–dermatologist density areas. Associations are difficult to characterize without historical staging data aggregated from large registries. We hypothesized that decreased MCC survival is associated with rural counties.”

The researchers used 18 registries from the November 2019 SEER database to retrospectively evaluate adults who were diagnosed with MCC between 2004 and 2015 as confirmed by positive histology. Study endpoints were SEER historic stage at diagnosis and 5-year survival. MCC cases were stratified by 2013 USDA urban-rural continuum codes, which defines metropolitan counties as those with a population of 1 million or more, urban counties as those with a population of less than 1 million, and rural counties as nonmetropolitan counties not adjacent to a metropolitan area.

A total of 6,291 cases with a mean age of 75 years were included in the final analysis: 3,750 from metro areas, 2,235 from urban areas, and 306 from rural areas. A higher proportion of MCC patients from rural areas were male (69% vs. 62% from metro areas and 64% from urban areas) and white (97% vs. 95% and 96%, respectively). “This may contribute to differences in MCC care,” Dr. Larson said. “However, we also found that there is an increased incidence of locally staged disease in rural areas (51%) than in metro (44%) or urban (45%) areas (P = .02). In addition, fewer lymph node surgeries were performed in rural (50%) and urban (51%) areas than in metro areas (45%; P = .01).”

Overall survival was worse among patients in rural areas (a mean of 34 months), compared with those in urban (a mean of 41 months) and metro areas (a mean of 47 months; P = .02). “This may be due to the fact that rural counties have the higher risk factors for MCC incidence and death, but when we account for the confounders, including sex, age, race, and MCC stage, we still found a difference in overall survival in rural counties, compared to metro and urban counties,” Dr. Larson said.

Dr. Carroll, an associate professor of dermatology at University Hospitals of Cleveland, characterized the finding as “not what you’d expect with a higher incidence of local disease. Therefore, there is the potential for mis-staging in rural counties, where we did see that the interrogation of lymph nodes was done less frequently than in urban centers, which were more aligned with National Comprehensive Cancer Network guidelines during this time period. Still, after correction, rural location is still associated with a higher MCC mortality. There is a need for us to further interrogate what the causes are for this disparity in care between rural and urban centers.”

The other study authors were Dustin DeMeo and Christian Scheufele, MD. The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

There is an increased incidence of locally staged Merkel cell carcinoma (MCC) among patients who live in rural areas of the United States, compared with those in urban and metropolitan areas, yet overall survival is worse in rural areas.

This paradox was discovered in an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program that primary author Bryan T. Carroll, MD, PhD, and colleagues presented during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

“MCC is a rare and aggressive neoplasm of the skin with high mortality,” said coauthor Emma Larson, MD, a dermatology clinical research fellow at University Hospitals of Cleveland. “Previous studies have demonstrated that MCC survival is lower in low–dermatologist density areas. Associations are difficult to characterize without historical staging data aggregated from large registries. We hypothesized that decreased MCC survival is associated with rural counties.”

The researchers used 18 registries from the November 2019 SEER database to retrospectively evaluate adults who were diagnosed with MCC between 2004 and 2015 as confirmed by positive histology. Study endpoints were SEER historic stage at diagnosis and 5-year survival. MCC cases were stratified by 2013 USDA urban-rural continuum codes, which defines metropolitan counties as those with a population of 1 million or more, urban counties as those with a population of less than 1 million, and rural counties as nonmetropolitan counties not adjacent to a metropolitan area.

A total of 6,291 cases with a mean age of 75 years were included in the final analysis: 3,750 from metro areas, 2,235 from urban areas, and 306 from rural areas. A higher proportion of MCC patients from rural areas were male (69% vs. 62% from metro areas and 64% from urban areas) and white (97% vs. 95% and 96%, respectively). “This may contribute to differences in MCC care,” Dr. Larson said. “However, we also found that there is an increased incidence of locally staged disease in rural areas (51%) than in metro (44%) or urban (45%) areas (P = .02). In addition, fewer lymph node surgeries were performed in rural (50%) and urban (51%) areas than in metro areas (45%; P = .01).”

Overall survival was worse among patients in rural areas (a mean of 34 months), compared with those in urban (a mean of 41 months) and metro areas (a mean of 47 months; P = .02). “This may be due to the fact that rural counties have the higher risk factors for MCC incidence and death, but when we account for the confounders, including sex, age, race, and MCC stage, we still found a difference in overall survival in rural counties, compared to metro and urban counties,” Dr. Larson said.

Dr. Carroll, an associate professor of dermatology at University Hospitals of Cleveland, characterized the finding as “not what you’d expect with a higher incidence of local disease. Therefore, there is the potential for mis-staging in rural counties, where we did see that the interrogation of lymph nodes was done less frequently than in urban centers, which were more aligned with National Comprehensive Cancer Network guidelines during this time period. Still, after correction, rural location is still associated with a higher MCC mortality. There is a need for us to further interrogate what the causes are for this disparity in care between rural and urban centers.”

The other study authors were Dustin DeMeo and Christian Scheufele, MD. The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

There is an increased incidence of locally staged Merkel cell carcinoma (MCC) among patients who live in rural areas of the United States, compared with those in urban and metropolitan areas, yet overall survival is worse in rural areas.

This paradox was discovered in an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program that primary author Bryan T. Carroll, MD, PhD, and colleagues presented during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

“MCC is a rare and aggressive neoplasm of the skin with high mortality,” said coauthor Emma Larson, MD, a dermatology clinical research fellow at University Hospitals of Cleveland. “Previous studies have demonstrated that MCC survival is lower in low–dermatologist density areas. Associations are difficult to characterize without historical staging data aggregated from large registries. We hypothesized that decreased MCC survival is associated with rural counties.”

The researchers used 18 registries from the November 2019 SEER database to retrospectively evaluate adults who were diagnosed with MCC between 2004 and 2015 as confirmed by positive histology. Study endpoints were SEER historic stage at diagnosis and 5-year survival. MCC cases were stratified by 2013 USDA urban-rural continuum codes, which defines metropolitan counties as those with a population of 1 million or more, urban counties as those with a population of less than 1 million, and rural counties as nonmetropolitan counties not adjacent to a metropolitan area.

A total of 6,291 cases with a mean age of 75 years were included in the final analysis: 3,750 from metro areas, 2,235 from urban areas, and 306 from rural areas. A higher proportion of MCC patients from rural areas were male (69% vs. 62% from metro areas and 64% from urban areas) and white (97% vs. 95% and 96%, respectively). “This may contribute to differences in MCC care,” Dr. Larson said. “However, we also found that there is an increased incidence of locally staged disease in rural areas (51%) than in metro (44%) or urban (45%) areas (P = .02). In addition, fewer lymph node surgeries were performed in rural (50%) and urban (51%) areas than in metro areas (45%; P = .01).”

Overall survival was worse among patients in rural areas (a mean of 34 months), compared with those in urban (a mean of 41 months) and metro areas (a mean of 47 months; P = .02). “This may be due to the fact that rural counties have the higher risk factors for MCC incidence and death, but when we account for the confounders, including sex, age, race, and MCC stage, we still found a difference in overall survival in rural counties, compared to metro and urban counties,” Dr. Larson said.

Dr. Carroll, an associate professor of dermatology at University Hospitals of Cleveland, characterized the finding as “not what you’d expect with a higher incidence of local disease. Therefore, there is the potential for mis-staging in rural counties, where we did see that the interrogation of lymph nodes was done less frequently than in urban centers, which were more aligned with National Comprehensive Cancer Network guidelines during this time period. Still, after correction, rural location is still associated with a higher MCC mortality. There is a need for us to further interrogate what the causes are for this disparity in care between rural and urban centers.”

The other study authors were Dustin DeMeo and Christian Scheufele, MD. The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

An updated recommendation from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) calling for universal hepatitis B vaccination of all adults aged 59 and younger has boosted the call to improve clinicians’ awareness of the increasing infection and low vaccination rates – and raise the issue with patients.

“This new recommendation from [the] ACIP will be instrumental [in] raising adult hepatitis B vaccination rates in the U.S. to levels that will allow us to finally eliminate hepatitis B in this country,” said Rita K. Kuwahara, MD, a primary care internal medicine physician and health policy fellow at Georgetown University, in Washington, D.C., in addressing the issue at the U.S. Conference on HIV/AIDS (USCHA) this month.

“We have the tools to prevent hepatitis B, and since we have such safe and highly effective vaccines to protect against community [spread], we should not have a single new infection in our nation,” she asserted.

The unanimously approved updated ACIP recommendation was issued in November and still requires adoption by the CDC director. The ACIP specifically recommends that adults aged 19 to 59 and those 60 years and older with risk factors for infection “should” receive the hepatitis B vaccine, and it further stipulates that those 60 years and older without known risk factors for hepatitis B “may” receive the vaccine.

The recommendation was previously only for adults at risk for hepatitis B infection due to a variety of factors, including sexual exposure, percutaneous or mucosal exposure to blood, hepatitis C infection, chronic liver disease, end-stage renal disease, and HIV infection.

“The number of risk factors was long, and for a busy primary care provider to have to go through a lengthy risk-based protocol like that, it may not happen,” Dr. Kuwahara told this news organization.

“Now we have a really helpful new recommendation that is simply age based, and clinicians can just tell patients that if they were born before this certain period, a hepatitis B vaccination is recommended.”

The change comes amid a troubling trajectory of hepatitis B, with up to 2.4 million individuals currently having chronic hepatitis B in the U.S. and infection rates soaring by 100% to more than 400% in states with high opioid use, such as West Virginia, Kentucky, Tennessee, and Maine, Dr. Kuwahara said.

Notably, hepatitis B is the leading cause of liver disease, and one in four individuals with unmanaged chronic hepatitis B goes on to develop liver failure and/or cirrhosis or liver cancer, which has a 5-year survival rate of only 18%.

Despite the rising infection rates, only 25%-30% of adults in the U.S. are reported to be currently vaccinated for hepatitis B, even though safe and highly effective vaccines are available, notably including a new two-dose vaccine (Heplisav-B) that can be provided over just a month (vs. other hepatitis B vaccines requiring 3 doses over 6 months).
 

Clinician awareness of low vaccination rates lacking

Dr. Kuwahara noted that awareness among clinicians of the issues surrounding hepatitis B appears low, with one small survey that she and her colleagues conducted of 30 primary care physicians showing that not one of the respondents was aware of the low vaccination rate.

Dr. Kuwahara says a key reason for the low awareness to discuss the hepatitis B vaccination with adults is the common impression that the responsibility for the vaccination lies in the hands of pediatricians.

But that’s only half correct – universal vaccination for hepatitis B in all infants and children is indeed currently the policy in the U.S. – but that was not implemented in all states until the mid-to-late ‘90s, meaning the millions of adults over the age of about 25 to 30, born before that period, are likely not fully vaccinated against hepatitis B.

“When I was in medical school, there wasn’t a lot of discussion of how low the hepatitis B vaccination rate was because everyone knew there was universal childhood vaccination, and I think there was an assumption that it had been going on for a long time,” Dr. Kuwahara said. “So I think it’s clearly a misconception, and it’s really important to improve clinician awareness around the issue.”
 

Opioid use a key factor in rising infection rates

Importantly, a large proportion of opioid users are among the population of patients born before the mid-’90s – and those adults have a particularly high risk of transmission, with data indicating that 36% of new hepatitis B infections are the result of the opioid epidemic, Dr. Kuwahara noted.

“In the opioid epidemic, we have seen some of the greatest increases in acute hepatitis B presenting in adults aged 30 to 49 years old, as most adults in this age range would not have been vaccinated as children in the U.S.,” she said.

Approximately two-thirds of individuals with chronic hepatitis B are reportedly not even aware of their infection status due to ineffective prevention and vaccination programs, adding to the spread of infection, Dr. Kuwahara said.

Meanwhile, COVID-19 has only exacerbated the problem, with record-high instances of overdoses and overdose-related deaths during the pandemic, she explained.

However, the pandemic, and specifically the sweeping innovations that have been implemented in desperate efforts to bring COVID-19 vaccines to the public, could in fact represent a critical opportunity for hepatitis B prevention, Dr. Kuwahara said.

“Significant resources and federal funding have already been invested to develop a robust infrastructure for multi-dose COVID-19 vaccine administration during the pandemic, which has resulted in millions of people across the U.S. receiving the COVID-19 vaccine in easily accessible settings within their communities,” she said.

“It is essential that we expand the infrastructure development ... so that we may use this infrastructure to administer other vaccines such as the hepatitis B vaccine to adults throughout the nation and prevent additional outbreaks.”
 

Implementation of vaccine recommendations key

Dr. Kuwahara outlined key measures that will be important in implementing the hepatitis B vaccine recommendations:

• Awareness of the hepatitis B vaccination recommendations at the primary care level: “The first step in implementing universal [guidelines] will be to ensure that health care providers, particularly in primary care, are aware of the new ACIP guidelines so that they can speak with their patients about this and appropriately order hepatitis B testing and vaccination,” she said.
• Availability of vaccines: In addition to making sure primary care clinics are well stocked with hepatitis B vaccines, the vaccines should also be available in pharmacies and other convenient nonclinical settings through community outreach, similar to COVID-19 vaccines.
• Follow-up: Systems should be established to remind patients to receive follow-up doses.
• Public funding for vaccines: Policy changes will need to occur to allocate appropriate Section 317 funding to provide hepatitis B vaccines to adults without health insurance coverage, Dr. Kuwahara said, underscoring concerns about health equity in vaccination.
• Track vaccinations: Communication should be established between places administering vaccines and primary care providers to make sure that vaccination status can be documented in a reliable setting.

Dr. Kuwahara also noted that a federal immunization information system will be essential to track vaccines across a lifespan, providing one integrated vaccine record that can be accessed even when patients travel or move to different states.

Commenting on the issue, Frank Hood, manager of hepatitis advocacy for The AIDS Institute in Washington, D.C., added that, in addition to simplifying the process, the new age-based recommendation removes the issue of perceived judgement from the advice.

“The previous recommendations were more risk based, and patients may tend to say ‘oh, I don’t have any of those behaviors,’ and there can be some stigma,” he said. “But having something that says everyone in these age groups should be or may be vaccinated just makes it much easier and covers a greater number of individuals.”

Mr. Hood further underscored the need for continued diligence in improving measures to prevent and eradicate HBV as well as other infectious diseases.

“It is imperative that the systems being built now to respond to future infectious disease outbreaks are done so in a way to equitably support the efforts and end goal of eliminating current infectious disease epidemics like viral hepatitis and HIV,” he emphasized.“Elimination can’t be achieved if we leave people behind.”

Dr. Kuwahara and Mr. Hood had no disclosures to report.

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

An updated recommendation from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) calling for universal hepatitis B vaccination of all adults aged 59 and younger has boosted the call to improve clinicians’ awareness of the increasing infection and low vaccination rates – and raise the issue with patients.

“This new recommendation from [the] ACIP will be instrumental [in] raising adult hepatitis B vaccination rates in the U.S. to levels that will allow us to finally eliminate hepatitis B in this country,” said Rita K. Kuwahara, MD, a primary care internal medicine physician and health policy fellow at Georgetown University, in Washington, D.C., in addressing the issue at the U.S. Conference on HIV/AIDS (USCHA) this month.

“We have the tools to prevent hepatitis B, and since we have such safe and highly effective vaccines to protect against community [spread], we should not have a single new infection in our nation,” she asserted.

The unanimously approved updated ACIP recommendation was issued in November and still requires adoption by the CDC director. The ACIP specifically recommends that adults aged 19 to 59 and those 60 years and older with risk factors for infection “should” receive the hepatitis B vaccine, and it further stipulates that those 60 years and older without known risk factors for hepatitis B “may” receive the vaccine.

The recommendation was previously only for adults at risk for hepatitis B infection due to a variety of factors, including sexual exposure, percutaneous or mucosal exposure to blood, hepatitis C infection, chronic liver disease, end-stage renal disease, and HIV infection.

“The number of risk factors was long, and for a busy primary care provider to have to go through a lengthy risk-based protocol like that, it may not happen,” Dr. Kuwahara told this news organization.

“Now we have a really helpful new recommendation that is simply age based, and clinicians can just tell patients that if they were born before this certain period, a hepatitis B vaccination is recommended.”

The change comes amid a troubling trajectory of hepatitis B, with up to 2.4 million individuals currently having chronic hepatitis B in the U.S. and infection rates soaring by 100% to more than 400% in states with high opioid use, such as West Virginia, Kentucky, Tennessee, and Maine, Dr. Kuwahara said.

Notably, hepatitis B is the leading cause of liver disease, and one in four individuals with unmanaged chronic hepatitis B goes on to develop liver failure and/or cirrhosis or liver cancer, which has a 5-year survival rate of only 18%.

Despite the rising infection rates, only 25%-30% of adults in the U.S. are reported to be currently vaccinated for hepatitis B, even though safe and highly effective vaccines are available, notably including a new two-dose vaccine (Heplisav-B) that can be provided over just a month (vs. other hepatitis B vaccines requiring 3 doses over 6 months).
 

Clinician awareness of low vaccination rates lacking

Dr. Kuwahara noted that awareness among clinicians of the issues surrounding hepatitis B appears low, with one small survey that she and her colleagues conducted of 30 primary care physicians showing that not one of the respondents was aware of the low vaccination rate.

Dr. Kuwahara says a key reason for the low awareness to discuss the hepatitis B vaccination with adults is the common impression that the responsibility for the vaccination lies in the hands of pediatricians.

But that’s only half correct – universal vaccination for hepatitis B in all infants and children is indeed currently the policy in the U.S. – but that was not implemented in all states until the mid-to-late ‘90s, meaning the millions of adults over the age of about 25 to 30, born before that period, are likely not fully vaccinated against hepatitis B.

“When I was in medical school, there wasn’t a lot of discussion of how low the hepatitis B vaccination rate was because everyone knew there was universal childhood vaccination, and I think there was an assumption that it had been going on for a long time,” Dr. Kuwahara said. “So I think it’s clearly a misconception, and it’s really important to improve clinician awareness around the issue.”
 

Opioid use a key factor in rising infection rates

Importantly, a large proportion of opioid users are among the population of patients born before the mid-’90s – and those adults have a particularly high risk of transmission, with data indicating that 36% of new hepatitis B infections are the result of the opioid epidemic, Dr. Kuwahara noted.

“In the opioid epidemic, we have seen some of the greatest increases in acute hepatitis B presenting in adults aged 30 to 49 years old, as most adults in this age range would not have been vaccinated as children in the U.S.,” she said.

Approximately two-thirds of individuals with chronic hepatitis B are reportedly not even aware of their infection status due to ineffective prevention and vaccination programs, adding to the spread of infection, Dr. Kuwahara said.

Meanwhile, COVID-19 has only exacerbated the problem, with record-high instances of overdoses and overdose-related deaths during the pandemic, she explained.

However, the pandemic, and specifically the sweeping innovations that have been implemented in desperate efforts to bring COVID-19 vaccines to the public, could in fact represent a critical opportunity for hepatitis B prevention, Dr. Kuwahara said.

“Significant resources and federal funding have already been invested to develop a robust infrastructure for multi-dose COVID-19 vaccine administration during the pandemic, which has resulted in millions of people across the U.S. receiving the COVID-19 vaccine in easily accessible settings within their communities,” she said.

“It is essential that we expand the infrastructure development ... so that we may use this infrastructure to administer other vaccines such as the hepatitis B vaccine to adults throughout the nation and prevent additional outbreaks.”
 

Implementation of vaccine recommendations key

Dr. Kuwahara outlined key measures that will be important in implementing the hepatitis B vaccine recommendations:

• Awareness of the hepatitis B vaccination recommendations at the primary care level: “The first step in implementing universal [guidelines] will be to ensure that health care providers, particularly in primary care, are aware of the new ACIP guidelines so that they can speak with their patients about this and appropriately order hepatitis B testing and vaccination,” she said.
• Availability of vaccines: In addition to making sure primary care clinics are well stocked with hepatitis B vaccines, the vaccines should also be available in pharmacies and other convenient nonclinical settings through community outreach, similar to COVID-19 vaccines.
• Follow-up: Systems should be established to remind patients to receive follow-up doses.
• Public funding for vaccines: Policy changes will need to occur to allocate appropriate Section 317 funding to provide hepatitis B vaccines to adults without health insurance coverage, Dr. Kuwahara said, underscoring concerns about health equity in vaccination.
• Track vaccinations: Communication should be established between places administering vaccines and primary care providers to make sure that vaccination status can be documented in a reliable setting.

Dr. Kuwahara also noted that a federal immunization information system will be essential to track vaccines across a lifespan, providing one integrated vaccine record that can be accessed even when patients travel or move to different states.

Commenting on the issue, Frank Hood, manager of hepatitis advocacy for The AIDS Institute in Washington, D.C., added that, in addition to simplifying the process, the new age-based recommendation removes the issue of perceived judgement from the advice.

“The previous recommendations were more risk based, and patients may tend to say ‘oh, I don’t have any of those behaviors,’ and there can be some stigma,” he said. “But having something that says everyone in these age groups should be or may be vaccinated just makes it much easier and covers a greater number of individuals.”

Mr. Hood further underscored the need for continued diligence in improving measures to prevent and eradicate HBV as well as other infectious diseases.

“It is imperative that the systems being built now to respond to future infectious disease outbreaks are done so in a way to equitably support the efforts and end goal of eliminating current infectious disease epidemics like viral hepatitis and HIV,” he emphasized.“Elimination can’t be achieved if we leave people behind.”

Dr. Kuwahara and Mr. Hood had no disclosures to report.

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

An updated recommendation from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) calling for universal hepatitis B vaccination of all adults aged 59 and younger has boosted the call to improve clinicians’ awareness of the increasing infection and low vaccination rates – and raise the issue with patients.

“This new recommendation from [the] ACIP will be instrumental [in] raising adult hepatitis B vaccination rates in the U.S. to levels that will allow us to finally eliminate hepatitis B in this country,” said Rita K. Kuwahara, MD, a primary care internal medicine physician and health policy fellow at Georgetown University, in Washington, D.C., in addressing the issue at the U.S. Conference on HIV/AIDS (USCHA) this month.

“We have the tools to prevent hepatitis B, and since we have such safe and highly effective vaccines to protect against community [spread], we should not have a single new infection in our nation,” she asserted.

The unanimously approved updated ACIP recommendation was issued in November and still requires adoption by the CDC director. The ACIP specifically recommends that adults aged 19 to 59 and those 60 years and older with risk factors for infection “should” receive the hepatitis B vaccine, and it further stipulates that those 60 years and older without known risk factors for hepatitis B “may” receive the vaccine.

The recommendation was previously only for adults at risk for hepatitis B infection due to a variety of factors, including sexual exposure, percutaneous or mucosal exposure to blood, hepatitis C infection, chronic liver disease, end-stage renal disease, and HIV infection.

“The number of risk factors was long, and for a busy primary care provider to have to go through a lengthy risk-based protocol like that, it may not happen,” Dr. Kuwahara told this news organization.

“Now we have a really helpful new recommendation that is simply age based, and clinicians can just tell patients that if they were born before this certain period, a hepatitis B vaccination is recommended.”

The change comes amid a troubling trajectory of hepatitis B, with up to 2.4 million individuals currently having chronic hepatitis B in the U.S. and infection rates soaring by 100% to more than 400% in states with high opioid use, such as West Virginia, Kentucky, Tennessee, and Maine, Dr. Kuwahara said.

Notably, hepatitis B is the leading cause of liver disease, and one in four individuals with unmanaged chronic hepatitis B goes on to develop liver failure and/or cirrhosis or liver cancer, which has a 5-year survival rate of only 18%.

Despite the rising infection rates, only 25%-30% of adults in the U.S. are reported to be currently vaccinated for hepatitis B, even though safe and highly effective vaccines are available, notably including a new two-dose vaccine (Heplisav-B) that can be provided over just a month (vs. other hepatitis B vaccines requiring 3 doses over 6 months).
 

Clinician awareness of low vaccination rates lacking

Dr. Kuwahara noted that awareness among clinicians of the issues surrounding hepatitis B appears low, with one small survey that she and her colleagues conducted of 30 primary care physicians showing that not one of the respondents was aware of the low vaccination rate.

Dr. Kuwahara says a key reason for the low awareness to discuss the hepatitis B vaccination with adults is the common impression that the responsibility for the vaccination lies in the hands of pediatricians.

But that’s only half correct – universal vaccination for hepatitis B in all infants and children is indeed currently the policy in the U.S. – but that was not implemented in all states until the mid-to-late ‘90s, meaning the millions of adults over the age of about 25 to 30, born before that period, are likely not fully vaccinated against hepatitis B.

“When I was in medical school, there wasn’t a lot of discussion of how low the hepatitis B vaccination rate was because everyone knew there was universal childhood vaccination, and I think there was an assumption that it had been going on for a long time,” Dr. Kuwahara said. “So I think it’s clearly a misconception, and it’s really important to improve clinician awareness around the issue.”
 

Opioid use a key factor in rising infection rates

Importantly, a large proportion of opioid users are among the population of patients born before the mid-’90s – and those adults have a particularly high risk of transmission, with data indicating that 36% of new hepatitis B infections are the result of the opioid epidemic, Dr. Kuwahara noted.

“In the opioid epidemic, we have seen some of the greatest increases in acute hepatitis B presenting in adults aged 30 to 49 years old, as most adults in this age range would not have been vaccinated as children in the U.S.,” she said.

Approximately two-thirds of individuals with chronic hepatitis B are reportedly not even aware of their infection status due to ineffective prevention and vaccination programs, adding to the spread of infection, Dr. Kuwahara said.

Meanwhile, COVID-19 has only exacerbated the problem, with record-high instances of overdoses and overdose-related deaths during the pandemic, she explained.

However, the pandemic, and specifically the sweeping innovations that have been implemented in desperate efforts to bring COVID-19 vaccines to the public, could in fact represent a critical opportunity for hepatitis B prevention, Dr. Kuwahara said.

“Significant resources and federal funding have already been invested to develop a robust infrastructure for multi-dose COVID-19 vaccine administration during the pandemic, which has resulted in millions of people across the U.S. receiving the COVID-19 vaccine in easily accessible settings within their communities,” she said.

“It is essential that we expand the infrastructure development ... so that we may use this infrastructure to administer other vaccines such as the hepatitis B vaccine to adults throughout the nation and prevent additional outbreaks.”
 

Implementation of vaccine recommendations key

Dr. Kuwahara outlined key measures that will be important in implementing the hepatitis B vaccine recommendations:

• Awareness of the hepatitis B vaccination recommendations at the primary care level: “The first step in implementing universal [guidelines] will be to ensure that health care providers, particularly in primary care, are aware of the new ACIP guidelines so that they can speak with their patients about this and appropriately order hepatitis B testing and vaccination,” she said.
• Availability of vaccines: In addition to making sure primary care clinics are well stocked with hepatitis B vaccines, the vaccines should also be available in pharmacies and other convenient nonclinical settings through community outreach, similar to COVID-19 vaccines.
• Follow-up: Systems should be established to remind patients to receive follow-up doses.
• Public funding for vaccines: Policy changes will need to occur to allocate appropriate Section 317 funding to provide hepatitis B vaccines to adults without health insurance coverage, Dr. Kuwahara said, underscoring concerns about health equity in vaccination.
• Track vaccinations: Communication should be established between places administering vaccines and primary care providers to make sure that vaccination status can be documented in a reliable setting.

Dr. Kuwahara also noted that a federal immunization information system will be essential to track vaccines across a lifespan, providing one integrated vaccine record that can be accessed even when patients travel or move to different states.

Commenting on the issue, Frank Hood, manager of hepatitis advocacy for The AIDS Institute in Washington, D.C., added that, in addition to simplifying the process, the new age-based recommendation removes the issue of perceived judgement from the advice.

“The previous recommendations were more risk based, and patients may tend to say ‘oh, I don’t have any of those behaviors,’ and there can be some stigma,” he said. “But having something that says everyone in these age groups should be or may be vaccinated just makes it much easier and covers a greater number of individuals.”

Mr. Hood further underscored the need for continued diligence in improving measures to prevent and eradicate HBV as well as other infectious diseases.

“It is imperative that the systems being built now to respond to future infectious disease outbreaks are done so in a way to equitably support the efforts and end goal of eliminating current infectious disease epidemics like viral hepatitis and HIV,” he emphasized.“Elimination can’t be achieved if we leave people behind.”

Dr. Kuwahara and Mr. Hood had no disclosures to report.

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

The majority of addiction specialists, including psychiatrists, believe psychedelics are promising for the treatment of substance use disorders (SUDs) and psychiatric illnesses and, with some caveats, support legalization of the substances for these indications, results of a new survey show.

This strong positive attitude is “a surprise” given previous wariness of addiction specialists regarding legalization of marijuana, noted study investigator Amanda Kim, MD, JD, of Brigham and Women’s Hospital and Harvard Medical School, Boston.

“We had hypothesized that addiction specialists would express more skepticism about psychedelics compared to nonaddiction specialists,” Dr. Kim said.

Instead, addiction experts who participated in the survey were very much in favor of psychedelics being legalized for therapeutic use, but only in a controlled setting.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry.
 

Growing interest

In recent years, there has been increased interest in the scientific community and among the general public in the therapeutic potential of psychedelics, said Dr. Kim. Previous research has shown growing positivity about psychedelics and support for their legalization among psychiatrists, she added.

Psychedelics have been decriminalized and/or legalized in several jurisdictions. The Food and Drug Administration has granted breakthrough therapy designation for 3,4-methylenedioxymethamphetamine (MDMA) in the treatment of posttraumatic stress disorder (PTSD) and has granted the same designation to psilocybin in the treatment of major depressive disorder.

“Despite psychedelics increasingly entering the mainstream, we are unaware of any studies specifically assessing the current attitudes of physicians specializing in addictions regarding psychedelics,” Dr. Kim said.

For the study, investigators identified prospective survey participants from the AAAP directory. They also reached out to program directors of addiction medicine and addiction psychiatry fellowships.

In the anonymous online survey, respondents were asked to rate their level of agreement with 30 statements.

The analysis included 145 respondents (59% men; mean age, 46.2 years). Psychiatrists made up about two-thirds of the sample. The remainder specialized in internal and family medicine.

Most respondents had some clinical exposure to psychedelics. Almost 85% reported discussing a psychedelic experience with at least one patient.
 

Positive attitudes, concerns

Overall, participants expressed very positive attitudes regarding the therapeutic use of psychedelics. About 64% strongly agreed or agreed psychedelics show promise in treating SUDs, and 82% agreed they show promise in treating psychiatric disorders.

However, more than one-third of respondents (37.9%) expressed concern about the addictive potential of psychedelics. This is more than in previous research polling psychiatrists, possibly because the study’s “broad” definition of psychedelics included “nonclassic, nonserotonergic hallucinogens,” such as ketamine and MDMA, Dr. Kim noted.

Because ketamine and MDMA are both lumped into the hallucinogen category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), “and both are known to have addictive potential, this may have obscured participant responses,” she added.

Some 28% of participants expressed concern about psychedelic use increasing the risk for subsequent psychiatric disorders and long-term cognitive impairment.

Almost three-quarters (74.5%) believe the therapeutic use of psychedelics should be legalized. However, most wanted legal therapeutic psychedelics to be highly regulated and administered only in controlled settings with specially trained providers.

Almost half of the sample believed therapeutic psychedelics should be legal in a variety of different contexts and by non-Western providers, in accordance with indigenous and/or spiritual traditions.

One surprising finding was that most respondents believed patients would be keen on using psychedelics to treat SUDs, said Dr. Kim.

“This may reflect evolving attitudes of both providers and patients about psychedelics, and it will be interesting to further study attitudes of patients toward the use of psychedelics to treat SUD in the future,” she added.

Attitudes toward psychedelics were generally similar for psychiatrists and nonpsychiatrists; but psychiatrists expressed greater comfort in discussing them with patients and were more likely to have observed complications of psychedelics use in their practice.

Dr. Kim said the study’s limitations included the small sample size and possible selection bias, as those with more favorable views of psychedelics may have been more likely to respond.

The study was supported by the Source Research Foundation.

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

The majority of addiction specialists, including psychiatrists, believe psychedelics are promising for the treatment of substance use disorders (SUDs) and psychiatric illnesses and, with some caveats, support legalization of the substances for these indications, results of a new survey show.

This strong positive attitude is “a surprise” given previous wariness of addiction specialists regarding legalization of marijuana, noted study investigator Amanda Kim, MD, JD, of Brigham and Women’s Hospital and Harvard Medical School, Boston.

“We had hypothesized that addiction specialists would express more skepticism about psychedelics compared to nonaddiction specialists,” Dr. Kim said.

Instead, addiction experts who participated in the survey were very much in favor of psychedelics being legalized for therapeutic use, but only in a controlled setting.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry.
 

Growing interest

In recent years, there has been increased interest in the scientific community and among the general public in the therapeutic potential of psychedelics, said Dr. Kim. Previous research has shown growing positivity about psychedelics and support for their legalization among psychiatrists, she added.

Psychedelics have been decriminalized and/or legalized in several jurisdictions. The Food and Drug Administration has granted breakthrough therapy designation for 3,4-methylenedioxymethamphetamine (MDMA) in the treatment of posttraumatic stress disorder (PTSD) and has granted the same designation to psilocybin in the treatment of major depressive disorder.

“Despite psychedelics increasingly entering the mainstream, we are unaware of any studies specifically assessing the current attitudes of physicians specializing in addictions regarding psychedelics,” Dr. Kim said.

For the study, investigators identified prospective survey participants from the AAAP directory. They also reached out to program directors of addiction medicine and addiction psychiatry fellowships.

In the anonymous online survey, respondents were asked to rate their level of agreement with 30 statements.

The analysis included 145 respondents (59% men; mean age, 46.2 years). Psychiatrists made up about two-thirds of the sample. The remainder specialized in internal and family medicine.

Most respondents had some clinical exposure to psychedelics. Almost 85% reported discussing a psychedelic experience with at least one patient.
 

Positive attitudes, concerns

Overall, participants expressed very positive attitudes regarding the therapeutic use of psychedelics. About 64% strongly agreed or agreed psychedelics show promise in treating SUDs, and 82% agreed they show promise in treating psychiatric disorders.

However, more than one-third of respondents (37.9%) expressed concern about the addictive potential of psychedelics. This is more than in previous research polling psychiatrists, possibly because the study’s “broad” definition of psychedelics included “nonclassic, nonserotonergic hallucinogens,” such as ketamine and MDMA, Dr. Kim noted.

Because ketamine and MDMA are both lumped into the hallucinogen category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), “and both are known to have addictive potential, this may have obscured participant responses,” she added.

Some 28% of participants expressed concern about psychedelic use increasing the risk for subsequent psychiatric disorders and long-term cognitive impairment.

Almost three-quarters (74.5%) believe the therapeutic use of psychedelics should be legalized. However, most wanted legal therapeutic psychedelics to be highly regulated and administered only in controlled settings with specially trained providers.

Almost half of the sample believed therapeutic psychedelics should be legal in a variety of different contexts and by non-Western providers, in accordance with indigenous and/or spiritual traditions.

One surprising finding was that most respondents believed patients would be keen on using psychedelics to treat SUDs, said Dr. Kim.

“This may reflect evolving attitudes of both providers and patients about psychedelics, and it will be interesting to further study attitudes of patients toward the use of psychedelics to treat SUD in the future,” she added.

Attitudes toward psychedelics were generally similar for psychiatrists and nonpsychiatrists; but psychiatrists expressed greater comfort in discussing them with patients and were more likely to have observed complications of psychedelics use in their practice.

Dr. Kim said the study’s limitations included the small sample size and possible selection bias, as those with more favorable views of psychedelics may have been more likely to respond.

The study was supported by the Source Research Foundation.

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

The majority of addiction specialists, including psychiatrists, believe psychedelics are promising for the treatment of substance use disorders (SUDs) and psychiatric illnesses and, with some caveats, support legalization of the substances for these indications, results of a new survey show.

This strong positive attitude is “a surprise” given previous wariness of addiction specialists regarding legalization of marijuana, noted study investigator Amanda Kim, MD, JD, of Brigham and Women’s Hospital and Harvard Medical School, Boston.

“We had hypothesized that addiction specialists would express more skepticism about psychedelics compared to nonaddiction specialists,” Dr. Kim said.

Instead, addiction experts who participated in the survey were very much in favor of psychedelics being legalized for therapeutic use, but only in a controlled setting.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry.
 

Growing interest

In recent years, there has been increased interest in the scientific community and among the general public in the therapeutic potential of psychedelics, said Dr. Kim. Previous research has shown growing positivity about psychedelics and support for their legalization among psychiatrists, she added.

Psychedelics have been decriminalized and/or legalized in several jurisdictions. The Food and Drug Administration has granted breakthrough therapy designation for 3,4-methylenedioxymethamphetamine (MDMA) in the treatment of posttraumatic stress disorder (PTSD) and has granted the same designation to psilocybin in the treatment of major depressive disorder.

“Despite psychedelics increasingly entering the mainstream, we are unaware of any studies specifically assessing the current attitudes of physicians specializing in addictions regarding psychedelics,” Dr. Kim said.

For the study, investigators identified prospective survey participants from the AAAP directory. They also reached out to program directors of addiction medicine and addiction psychiatry fellowships.

In the anonymous online survey, respondents were asked to rate their level of agreement with 30 statements.

The analysis included 145 respondents (59% men; mean age, 46.2 years). Psychiatrists made up about two-thirds of the sample. The remainder specialized in internal and family medicine.

Most respondents had some clinical exposure to psychedelics. Almost 85% reported discussing a psychedelic experience with at least one patient.
 

Positive attitudes, concerns

Overall, participants expressed very positive attitudes regarding the therapeutic use of psychedelics. About 64% strongly agreed or agreed psychedelics show promise in treating SUDs, and 82% agreed they show promise in treating psychiatric disorders.

However, more than one-third of respondents (37.9%) expressed concern about the addictive potential of psychedelics. This is more than in previous research polling psychiatrists, possibly because the study’s “broad” definition of psychedelics included “nonclassic, nonserotonergic hallucinogens,” such as ketamine and MDMA, Dr. Kim noted.

Because ketamine and MDMA are both lumped into the hallucinogen category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), “and both are known to have addictive potential, this may have obscured participant responses,” she added.

Some 28% of participants expressed concern about psychedelic use increasing the risk for subsequent psychiatric disorders and long-term cognitive impairment.

Almost three-quarters (74.5%) believe the therapeutic use of psychedelics should be legalized. However, most wanted legal therapeutic psychedelics to be highly regulated and administered only in controlled settings with specially trained providers.

Almost half of the sample believed therapeutic psychedelics should be legal in a variety of different contexts and by non-Western providers, in accordance with indigenous and/or spiritual traditions.

One surprising finding was that most respondents believed patients would be keen on using psychedelics to treat SUDs, said Dr. Kim.

“This may reflect evolving attitudes of both providers and patients about psychedelics, and it will be interesting to further study attitudes of patients toward the use of psychedelics to treat SUD in the future,” she added.

Attitudes toward psychedelics were generally similar for psychiatrists and nonpsychiatrists; but psychiatrists expressed greater comfort in discussing them with patients and were more likely to have observed complications of psychedelics use in their practice.

Dr. Kim said the study’s limitations included the small sample size and possible selection bias, as those with more favorable views of psychedelics may have been more likely to respond.

The study was supported by the Source Research Foundation.

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

The cardiovascular and cardiometabolic effects of therapy in women with breast cancer vary based on patient factors like weight and menopausal status, according to findings from the Pathways Heart Study recently presented at the San Antonio Breast Cancer Symposium.

Fred Hutchinson Cancer Center

For example, certain chemotherapy drugs may confer higher risk in breast cancer survivors of normal weight, whereas they may lower stroke risk in those who are obese, according to Heather Greenlee, ND, PhD, a public health researcher and naturopathic physician with the Fred Hutchinson Cancer Research Center in Seattle.

In postmenopausal women with breast cancer, aromatase inhibitors may increase cardiovascular risk, while tamoxifen appears to reduce the risk of incident dyslipidemia, she said.

The findings are from separate analyses of data from studies presented during a poster discussion session at the symposium.
 

Breast cancer treatment and cardiovascular effects: The role of weight

In one analysis, Dr. Greenlee and colleagues examined outcomes in 13,582 breast cancer survivors with a median age of 60 years and median follow-up of 7 years to assess whether cardiovascular disease (CVD) risk associated with specific breast cancer therapies varies by body mass index (BMI) category at diagnosis.

Many routinely used breast cancer therapies are cardiotoxic, and being overweight or obese are known risk factors for CVD, but few studies have assessed whether BMI modifies the effect of these treatment on cardiovascular risk, Dr. Greenlee explained.

After adjusting for baseline demographic and health-related factors, and other breast cancer treatment, they found that:

• Ischemic heart disease risk was higher among normal-weight women who received anthracyclines, compared with those who did not (hazard ratio, 4.2). No other risk associations were observed for other breast cancer therapies and BMI groups.
• Heart failure/cardiomyopathy risk was higher among women with normal weight who received anthracyclines, cyclophosphamides, or left-sided radiation, compared with those who did not (HRs, 5.24, 3.27, and 2.05, respectively), and among overweight women who received anthracyclines, compared with those who did not (HR, 2.18). No risk associations were observed for women who received trastuzumab, taxanes, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were obese.
• Stroke risk was higher in normal-weight women who received taxanes, cyclophosphamides, or left-sided radiation versus those who did not (HRs, 2.14, 2.35, and 1.31, respectively), and stroke risk was lower in obese women who received anthracyclines, taxanes, or cyclophosphamide, compared with those who did not (HRs, 0.32, 0.41, and 0.29, respectively). No risk associations were observed for trastuzumab, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were overweight.

The lack of associations noted between treatments and heart failure risk among obese patients could be caused by the “obesity paradox” observed in prior obese populations, the investigators noted, adding that additional analyses are planned to “examine whether different dosage and duration of breast cancer therapy exposures across the BMI groups contributed to these risk associations.”
 

Breast cancer treatment and cardiometabolic effects: The role of menopausal status

In a separate analysis, Dr. Greenlee and colleagues looked at the association between endocrine therapies and cardiometabolic risk based on menopausal status.

Endocrine therapy is associated with CVD in breast cancer survivors and may be associated with developing cardiometabolic risk factors like diabetes, dyslipidemia, and hypertension, they noted, explaining that tamoxifen has mixed estrogenic and antiestrogenic activity, while aromatase inhibitors deplete endogenous estrogen.

Since most studies have compared tamoxifen with aromatase inhibitor use, it has been a challenge challenging to discern the effects of each, Dr. Greenlee said.

She and her colleagues reviewed records for 14,942 breast cancer survivors who were diagnosed between 2005 and 2013. The patients had a mean age of 61 years at baseline, and 24.9% were premenopausal at the time of diagnosis. Of the premenopausal women, 27.3% used tamoxifen, 19.2% used aromatase inhibitors, and 53.5% did not use endocrine therapy, and of the postmenopausal women, 6.6% used tamoxifen, 47.7% used aromatase inhibitors, and 45.7% did not use endocrine therapy.

After adjusting for baseline demographics and health factors, the investigators found that:

• The use of tamoxifen or aromatase inhibitors was not associated with a risk of developing diabetes, dyslipidemia, or hypertension in premenopausal women, or with a risk of developing diabetes or hypertension in postmenopausal women.
• The risk of dyslipidemia was higher in postmenopausal aromatase inhibitor users, and lower in postmenopausal tamoxifen users, compared with postmenopausal non-users of endocrine therapy (HRs, 1.15 and 0.75, respectively).

The lack of associations between endocrine therapy and CVD risk in premenopausal women may be from low power, Dr. Greenlee said, noting that analyses in larger sample sizes are needed.

She and her colleagues plan to conduct further analyses looking at treatment dosage and duration, and comparing steroidal versus nonsteroidal aromatase inhibitors.

Future studies should examine the implications of these associations on long-term CVD and how best to manage lipid profiles in postmenopausal breast cancer survivors who have a history of endocrine therapy treatment, they concluded.

This research was funded by grants from the National Cancer Institute.

sworcester@mdedge.com

The cardiovascular and cardiometabolic effects of therapy in women with breast cancer vary based on patient factors like weight and menopausal status, according to findings from the Pathways Heart Study recently presented at the San Antonio Breast Cancer Symposium.

Fred Hutchinson Cancer Center

For example, certain chemotherapy drugs may confer higher risk in breast cancer survivors of normal weight, whereas they may lower stroke risk in those who are obese, according to Heather Greenlee, ND, PhD, a public health researcher and naturopathic physician with the Fred Hutchinson Cancer Research Center in Seattle.

In postmenopausal women with breast cancer, aromatase inhibitors may increase cardiovascular risk, while tamoxifen appears to reduce the risk of incident dyslipidemia, she said.

The findings are from separate analyses of data from studies presented during a poster discussion session at the symposium.
 

Breast cancer treatment and cardiovascular effects: The role of weight

In one analysis, Dr. Greenlee and colleagues examined outcomes in 13,582 breast cancer survivors with a median age of 60 years and median follow-up of 7 years to assess whether cardiovascular disease (CVD) risk associated with specific breast cancer therapies varies by body mass index (BMI) category at diagnosis.

Many routinely used breast cancer therapies are cardiotoxic, and being overweight or obese are known risk factors for CVD, but few studies have assessed whether BMI modifies the effect of these treatment on cardiovascular risk, Dr. Greenlee explained.

After adjusting for baseline demographic and health-related factors, and other breast cancer treatment, they found that:

• Ischemic heart disease risk was higher among normal-weight women who received anthracyclines, compared with those who did not (hazard ratio, 4.2). No other risk associations were observed for other breast cancer therapies and BMI groups.
• Heart failure/cardiomyopathy risk was higher among women with normal weight who received anthracyclines, cyclophosphamides, or left-sided radiation, compared with those who did not (HRs, 5.24, 3.27, and 2.05, respectively), and among overweight women who received anthracyclines, compared with those who did not (HR, 2.18). No risk associations were observed for women who received trastuzumab, taxanes, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were obese.
• Stroke risk was higher in normal-weight women who received taxanes, cyclophosphamides, or left-sided radiation versus those who did not (HRs, 2.14, 2.35, and 1.31, respectively), and stroke risk was lower in obese women who received anthracyclines, taxanes, or cyclophosphamide, compared with those who did not (HRs, 0.32, 0.41, and 0.29, respectively). No risk associations were observed for trastuzumab, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were overweight.

The lack of associations noted between treatments and heart failure risk among obese patients could be caused by the “obesity paradox” observed in prior obese populations, the investigators noted, adding that additional analyses are planned to “examine whether different dosage and duration of breast cancer therapy exposures across the BMI groups contributed to these risk associations.”
 

Breast cancer treatment and cardiometabolic effects: The role of menopausal status

In a separate analysis, Dr. Greenlee and colleagues looked at the association between endocrine therapies and cardiometabolic risk based on menopausal status.

Endocrine therapy is associated with CVD in breast cancer survivors and may be associated with developing cardiometabolic risk factors like diabetes, dyslipidemia, and hypertension, they noted, explaining that tamoxifen has mixed estrogenic and antiestrogenic activity, while aromatase inhibitors deplete endogenous estrogen.

Since most studies have compared tamoxifen with aromatase inhibitor use, it has been a challenge challenging to discern the effects of each, Dr. Greenlee said.

She and her colleagues reviewed records for 14,942 breast cancer survivors who were diagnosed between 2005 and 2013. The patients had a mean age of 61 years at baseline, and 24.9% were premenopausal at the time of diagnosis. Of the premenopausal women, 27.3% used tamoxifen, 19.2% used aromatase inhibitors, and 53.5% did not use endocrine therapy, and of the postmenopausal women, 6.6% used tamoxifen, 47.7% used aromatase inhibitors, and 45.7% did not use endocrine therapy.

After adjusting for baseline demographics and health factors, the investigators found that:

• The use of tamoxifen or aromatase inhibitors was not associated with a risk of developing diabetes, dyslipidemia, or hypertension in premenopausal women, or with a risk of developing diabetes or hypertension in postmenopausal women.
• The risk of dyslipidemia was higher in postmenopausal aromatase inhibitor users, and lower in postmenopausal tamoxifen users, compared with postmenopausal non-users of endocrine therapy (HRs, 1.15 and 0.75, respectively).

The lack of associations between endocrine therapy and CVD risk in premenopausal women may be from low power, Dr. Greenlee said, noting that analyses in larger sample sizes are needed.

She and her colleagues plan to conduct further analyses looking at treatment dosage and duration, and comparing steroidal versus nonsteroidal aromatase inhibitors.

Future studies should examine the implications of these associations on long-term CVD and how best to manage lipid profiles in postmenopausal breast cancer survivors who have a history of endocrine therapy treatment, they concluded.

This research was funded by grants from the National Cancer Institute.

sworcester@mdedge.com

The cardiovascular and cardiometabolic effects of therapy in women with breast cancer vary based on patient factors like weight and menopausal status, according to findings from the Pathways Heart Study recently presented at the San Antonio Breast Cancer Symposium.

Fred Hutchinson Cancer Center

For example, certain chemotherapy drugs may confer higher risk in breast cancer survivors of normal weight, whereas they may lower stroke risk in those who are obese, according to Heather Greenlee, ND, PhD, a public health researcher and naturopathic physician with the Fred Hutchinson Cancer Research Center in Seattle.

In postmenopausal women with breast cancer, aromatase inhibitors may increase cardiovascular risk, while tamoxifen appears to reduce the risk of incident dyslipidemia, she said.

The findings are from separate analyses of data from studies presented during a poster discussion session at the symposium.
 

Breast cancer treatment and cardiovascular effects: The role of weight

In one analysis, Dr. Greenlee and colleagues examined outcomes in 13,582 breast cancer survivors with a median age of 60 years and median follow-up of 7 years to assess whether cardiovascular disease (CVD) risk associated with specific breast cancer therapies varies by body mass index (BMI) category at diagnosis.

Many routinely used breast cancer therapies are cardiotoxic, and being overweight or obese are known risk factors for CVD, but few studies have assessed whether BMI modifies the effect of these treatment on cardiovascular risk, Dr. Greenlee explained.

After adjusting for baseline demographic and health-related factors, and other breast cancer treatment, they found that:

• Ischemic heart disease risk was higher among normal-weight women who received anthracyclines, compared with those who did not (hazard ratio, 4.2). No other risk associations were observed for other breast cancer therapies and BMI groups.
• Heart failure/cardiomyopathy risk was higher among women with normal weight who received anthracyclines, cyclophosphamides, or left-sided radiation, compared with those who did not (HRs, 5.24, 3.27, and 2.05, respectively), and among overweight women who received anthracyclines, compared with those who did not (HR, 2.18). No risk associations were observed for women who received trastuzumab, taxanes, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were obese.
• Stroke risk was higher in normal-weight women who received taxanes, cyclophosphamides, or left-sided radiation versus those who did not (HRs, 2.14, 2.35, and 1.31, respectively), and stroke risk was lower in obese women who received anthracyclines, taxanes, or cyclophosphamide, compared with those who did not (HRs, 0.32, 0.41, and 0.29, respectively). No risk associations were observed for trastuzumab, endocrine therapy, or radiation on any side, and no risk associations were observed for women who were overweight.

The lack of associations noted between treatments and heart failure risk among obese patients could be caused by the “obesity paradox” observed in prior obese populations, the investigators noted, adding that additional analyses are planned to “examine whether different dosage and duration of breast cancer therapy exposures across the BMI groups contributed to these risk associations.”
 

Breast cancer treatment and cardiometabolic effects: The role of menopausal status

In a separate analysis, Dr. Greenlee and colleagues looked at the association between endocrine therapies and cardiometabolic risk based on menopausal status.

Endocrine therapy is associated with CVD in breast cancer survivors and may be associated with developing cardiometabolic risk factors like diabetes, dyslipidemia, and hypertension, they noted, explaining that tamoxifen has mixed estrogenic and antiestrogenic activity, while aromatase inhibitors deplete endogenous estrogen.

Since most studies have compared tamoxifen with aromatase inhibitor use, it has been a challenge challenging to discern the effects of each, Dr. Greenlee said.

She and her colleagues reviewed records for 14,942 breast cancer survivors who were diagnosed between 2005 and 2013. The patients had a mean age of 61 years at baseline, and 24.9% were premenopausal at the time of diagnosis. Of the premenopausal women, 27.3% used tamoxifen, 19.2% used aromatase inhibitors, and 53.5% did not use endocrine therapy, and of the postmenopausal women, 6.6% used tamoxifen, 47.7% used aromatase inhibitors, and 45.7% did not use endocrine therapy.

After adjusting for baseline demographics and health factors, the investigators found that:

• The use of tamoxifen or aromatase inhibitors was not associated with a risk of developing diabetes, dyslipidemia, or hypertension in premenopausal women, or with a risk of developing diabetes or hypertension in postmenopausal women.
• The risk of dyslipidemia was higher in postmenopausal aromatase inhibitor users, and lower in postmenopausal tamoxifen users, compared with postmenopausal non-users of endocrine therapy (HRs, 1.15 and 0.75, respectively).

The lack of associations between endocrine therapy and CVD risk in premenopausal women may be from low power, Dr. Greenlee said, noting that analyses in larger sample sizes are needed.

She and her colleagues plan to conduct further analyses looking at treatment dosage and duration, and comparing steroidal versus nonsteroidal aromatase inhibitors.

Future studies should examine the implications of these associations on long-term CVD and how best to manage lipid profiles in postmenopausal breast cancer survivors who have a history of endocrine therapy treatment, they concluded.

This research was funded by grants from the National Cancer Institute.

sworcester@mdedge.com

Despite a flurry of publicity about its newfound cardiac risk profile, the antiseizure medication lamotrigine (Lamictal) is “still a good drug” in epilepsy and an excellent treatment for certain groups, New York University neurologist Jacqueline A. French, MD, told colleagues at the annual meeting of the American Epilepsy Society. But it’s now crucial to take special precautions in high-risk groups such as older people and heart patients.

“We need to plan more carefully when we use it, which we hate to do, as we know. But we’ve still got to do it,” said Dr. French, former president of the AES. “The risks are very small, but keep in mind that they’re not zero.”

In October 2020, the Food and Drug Administration added a warning to the lamotrigine label that said the drug “could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia.”

The FDA recommended avoiding the sodium channel blocker’s use “in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia.”

Later, in March 2021, the FDA announced that a review of in vitro findings “showed a potential increased risk of heart rhythm problems.”

As Dr. French noted, lamotrigine remains widely prescribed even though there’s “no pharmaceutical company out there pushing [it].” It’s an especially beneficial drug for certain groups such as the elderly and women of child-bearing age, she said.

But older people are also at higher risk of drug-related heart complications because of the fact that many already have cardiac disease, Dr. French said. She highlighted a 2005 trial of lamotrigine that found 48% of 593 patients aged 60 years and older had cardiac disease.
 

Special precautions

So what should neurologists know about prescribing lamotrigine in light of the new warning? Dr. French recommended guidelines that she cowrote with the AES and International League Against Epilepsy.

• Prescribe as normal in patients under 60 with no cardiac risk factors. In patients older than 60, or younger with risk factors, consider an EKG before prescribing lamotrigine.
• “Nonspecific EKG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning, and should not preclude these individuals from being prescribed lamotrigine.”
• Beware of higher risk and consider consulting a cardiologist before starting treatment in patients with second- or third-degree heart block, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, left bundle branch block, and right bundle branch block with left anterior or posterior fascicular block.
• “In most cases the initial EKG can be obtained while titrating, mainly when the individual is at the first dose of 25 mg/day because lamotrigine must be titrated slowly, and because cardiac adverse events are dose related.”
• “Clinicians should consider obtaining an EKG and/or cardiology consultation in people on lamotrigine with sudden-onset syncope or presyncope with loss of muscular tone without a clear vasovagal or orthostatic cause.”

Dr. French cautioned colleagues that they shouldn’t assume that lamotrigine stands alone among sodium channel blockers in terms of cardiac risk. As she noted, the FDA is asking manufacturers of other drugs in that class to provide data. “At some point, maybe sometime in the near future, we are going to hear in this particular in vitro sense how the other sodium channel blockers do stack up, compared with lamotrigine. At presence, in the absence of the availability of all of the rest of the data, it would be incorrect to presume that lamotrigine has more cardiac effects than other sodium channel blocking antiseizure medicines or all antiseizure medicines.”

For now, she said, although the guidelines are for lamotrigine, it’s “prudent” to follow them for all sodium channel blockers.

Dr. French reported no disclosures.

Despite a flurry of publicity about its newfound cardiac risk profile, the antiseizure medication lamotrigine (Lamictal) is “still a good drug” in epilepsy and an excellent treatment for certain groups, New York University neurologist Jacqueline A. French, MD, told colleagues at the annual meeting of the American Epilepsy Society. But it’s now crucial to take special precautions in high-risk groups such as older people and heart patients.

“We need to plan more carefully when we use it, which we hate to do, as we know. But we’ve still got to do it,” said Dr. French, former president of the AES. “The risks are very small, but keep in mind that they’re not zero.”

In October 2020, the Food and Drug Administration added a warning to the lamotrigine label that said the drug “could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia.”

The FDA recommended avoiding the sodium channel blocker’s use “in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia.”

Later, in March 2021, the FDA announced that a review of in vitro findings “showed a potential increased risk of heart rhythm problems.”

As Dr. French noted, lamotrigine remains widely prescribed even though there’s “no pharmaceutical company out there pushing [it].” It’s an especially beneficial drug for certain groups such as the elderly and women of child-bearing age, she said.

But older people are also at higher risk of drug-related heart complications because of the fact that many already have cardiac disease, Dr. French said. She highlighted a 2005 trial of lamotrigine that found 48% of 593 patients aged 60 years and older had cardiac disease.
 

Special precautions

So what should neurologists know about prescribing lamotrigine in light of the new warning? Dr. French recommended guidelines that she cowrote with the AES and International League Against Epilepsy.

• Prescribe as normal in patients under 60 with no cardiac risk factors. In patients older than 60, or younger with risk factors, consider an EKG before prescribing lamotrigine.
• “Nonspecific EKG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning, and should not preclude these individuals from being prescribed lamotrigine.”
• Beware of higher risk and consider consulting a cardiologist before starting treatment in patients with second- or third-degree heart block, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, left bundle branch block, and right bundle branch block with left anterior or posterior fascicular block.
• “In most cases the initial EKG can be obtained while titrating, mainly when the individual is at the first dose of 25 mg/day because lamotrigine must be titrated slowly, and because cardiac adverse events are dose related.”
• “Clinicians should consider obtaining an EKG and/or cardiology consultation in people on lamotrigine with sudden-onset syncope or presyncope with loss of muscular tone without a clear vasovagal or orthostatic cause.”

Dr. French cautioned colleagues that they shouldn’t assume that lamotrigine stands alone among sodium channel blockers in terms of cardiac risk. As she noted, the FDA is asking manufacturers of other drugs in that class to provide data. “At some point, maybe sometime in the near future, we are going to hear in this particular in vitro sense how the other sodium channel blockers do stack up, compared with lamotrigine. At presence, in the absence of the availability of all of the rest of the data, it would be incorrect to presume that lamotrigine has more cardiac effects than other sodium channel blocking antiseizure medicines or all antiseizure medicines.”

For now, she said, although the guidelines are for lamotrigine, it’s “prudent” to follow them for all sodium channel blockers.

Dr. French reported no disclosures.

Despite a flurry of publicity about its newfound cardiac risk profile, the antiseizure medication lamotrigine (Lamictal) is “still a good drug” in epilepsy and an excellent treatment for certain groups, New York University neurologist Jacqueline A. French, MD, told colleagues at the annual meeting of the American Epilepsy Society. But it’s now crucial to take special precautions in high-risk groups such as older people and heart patients.

“We need to plan more carefully when we use it, which we hate to do, as we know. But we’ve still got to do it,” said Dr. French, former president of the AES. “The risks are very small, but keep in mind that they’re not zero.”

In October 2020, the Food and Drug Administration added a warning to the lamotrigine label that said the drug “could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia.”

The FDA recommended avoiding the sodium channel blocker’s use “in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia.”

Later, in March 2021, the FDA announced that a review of in vitro findings “showed a potential increased risk of heart rhythm problems.”

As Dr. French noted, lamotrigine remains widely prescribed even though there’s “no pharmaceutical company out there pushing [it].” It’s an especially beneficial drug for certain groups such as the elderly and women of child-bearing age, she said.

But older people are also at higher risk of drug-related heart complications because of the fact that many already have cardiac disease, Dr. French said. She highlighted a 2005 trial of lamotrigine that found 48% of 593 patients aged 60 years and older had cardiac disease.
 

Special precautions

So what should neurologists know about prescribing lamotrigine in light of the new warning? Dr. French recommended guidelines that she cowrote with the AES and International League Against Epilepsy.

• Prescribe as normal in patients under 60 with no cardiac risk factors. In patients older than 60, or younger with risk factors, consider an EKG before prescribing lamotrigine.
• “Nonspecific EKG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning, and should not preclude these individuals from being prescribed lamotrigine.”
• Beware of higher risk and consider consulting a cardiologist before starting treatment in patients with second- or third-degree heart block, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, left bundle branch block, and right bundle branch block with left anterior or posterior fascicular block.
• “In most cases the initial EKG can be obtained while titrating, mainly when the individual is at the first dose of 25 mg/day because lamotrigine must be titrated slowly, and because cardiac adverse events are dose related.”
• “Clinicians should consider obtaining an EKG and/or cardiology consultation in people on lamotrigine with sudden-onset syncope or presyncope with loss of muscular tone without a clear vasovagal or orthostatic cause.”

Dr. French cautioned colleagues that they shouldn’t assume that lamotrigine stands alone among sodium channel blockers in terms of cardiac risk. As she noted, the FDA is asking manufacturers of other drugs in that class to provide data. “At some point, maybe sometime in the near future, we are going to hear in this particular in vitro sense how the other sodium channel blockers do stack up, compared with lamotrigine. At presence, in the absence of the availability of all of the rest of the data, it would be incorrect to presume that lamotrigine has more cardiac effects than other sodium channel blocking antiseizure medicines or all antiseizure medicines.”

For now, she said, although the guidelines are for lamotrigine, it’s “prudent” to follow them for all sodium channel blockers.

Dr. French reported no disclosures.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

An analysis of hospitalized patients with COVID-19 finds that those with no history of epilepsy had more than 3 times the odds of suffering a new-onset seizure than patients with epilepsy were to have breakthrough seizures (odds radio [OR] 3.15, P < .0001), researchers reported at the annual meeting of the American Epilepsy Society.

“If you have COVID and you have a seizure, it’s more likely that you’re having it for the first time, and it’s not as likely that you have epilepsy,” study lead author Neeraj Singh, MD, a neurologist at the New York-based Northwell Health system, said in an interview. “That’s new. We don’t normally see that when someone has a bacterial or viral infection. It’s demonstrating that this infection is having direct effect on the brain and brain signals.”

According to Dr. Singh, there’s little data about seizures in patients with COVID-19 because doctors have focused on other symptoms. A 2021 multicenter study found that electrographic seizures were detected in 9.6% of 197 patients with COVID-19 who were referred for cEEG.

For the new study, Dr. Singh and a colleague tracked 917 patients with COVID-19 in the Northwell Health system who were treated from Feb. 14 to June 14, 2020, with antiepileptic medication. Of the patients, 451 had a history of epilepsy, and 466 did not.

According to Dr. Singh, 27.6% of the patients without a history of epilepsy had new-onset seizures, while 10.1% of the patients with history of epilepsy had breakthrough seizures. The difference in odds was more than threefold after adjustment. (Among all COVID-19 patients, he said, perhaps 8%-16% had seizures).

The researchers also found that patients with new-onset seizures stayed in the hospital much longer (average, 26.9 days) than any patients with a known history of epilepsy (12.8 days, P < .0001, for those who had breakthrough seizures and 10.9 days, P < .0001, for those who didn’t).

In addition, the researchers found that having any seizures – new-onset or breakthrough – was linked to higher risk of death (OR 1.41, P = .03).

Antiseizure medications are key treatments for these patients, Dr. Singh said. As for the patients with new-onset seizures who recover from COVID-19, Dr. Singh said, “it’s suspected that these people are going to have a new diagnosis of epilepsy, not just a one-time seizure.”

The findings suggest that some patients with epilepsy are protected against COVID-19-related seizures because they take antiepileptic medications that “protect the brain from getting a trigger for an abnormal signal that leads to a seizure,” he said. “That’s one possibility.”

What can neurologists learn from the study? Dr. Singh recommends a “lower threshold” to recommend or approve EEGs in patients with COVID-19 who are confused/altered when they come in, especially if this is not normal. “They may actually be having silent seizures that no one’s noticing,” he said.

No study funding was reported. The authors reported no relevant disclosures.

An analysis of hospitalized patients with COVID-19 finds that those with no history of epilepsy had more than 3 times the odds of suffering a new-onset seizure than patients with epilepsy were to have breakthrough seizures (odds radio [OR] 3.15, P < .0001), researchers reported at the annual meeting of the American Epilepsy Society.

“If you have COVID and you have a seizure, it’s more likely that you’re having it for the first time, and it’s not as likely that you have epilepsy,” study lead author Neeraj Singh, MD, a neurologist at the New York-based Northwell Health system, said in an interview. “That’s new. We don’t normally see that when someone has a bacterial or viral infection. It’s demonstrating that this infection is having direct effect on the brain and brain signals.”

According to Dr. Singh, there’s little data about seizures in patients with COVID-19 because doctors have focused on other symptoms. A 2021 multicenter study found that electrographic seizures were detected in 9.6% of 197 patients with COVID-19 who were referred for cEEG.

For the new study, Dr. Singh and a colleague tracked 917 patients with COVID-19 in the Northwell Health system who were treated from Feb. 14 to June 14, 2020, with antiepileptic medication. Of the patients, 451 had a history of epilepsy, and 466 did not.

According to Dr. Singh, 27.6% of the patients without a history of epilepsy had new-onset seizures, while 10.1% of the patients with history of epilepsy had breakthrough seizures. The difference in odds was more than threefold after adjustment. (Among all COVID-19 patients, he said, perhaps 8%-16% had seizures).

The researchers also found that patients with new-onset seizures stayed in the hospital much longer (average, 26.9 days) than any patients with a known history of epilepsy (12.8 days, P < .0001, for those who had breakthrough seizures and 10.9 days, P < .0001, for those who didn’t).

In addition, the researchers found that having any seizures – new-onset or breakthrough – was linked to higher risk of death (OR 1.41, P = .03).

Antiseizure medications are key treatments for these patients, Dr. Singh said. As for the patients with new-onset seizures who recover from COVID-19, Dr. Singh said, “it’s suspected that these people are going to have a new diagnosis of epilepsy, not just a one-time seizure.”

The findings suggest that some patients with epilepsy are protected against COVID-19-related seizures because they take antiepileptic medications that “protect the brain from getting a trigger for an abnormal signal that leads to a seizure,” he said. “That’s one possibility.”

What can neurologists learn from the study? Dr. Singh recommends a “lower threshold” to recommend or approve EEGs in patients with COVID-19 who are confused/altered when they come in, especially if this is not normal. “They may actually be having silent seizures that no one’s noticing,” he said.

No study funding was reported. The authors reported no relevant disclosures.

An analysis of hospitalized patients with COVID-19 finds that those with no history of epilepsy had more than 3 times the odds of suffering a new-onset seizure than patients with epilepsy were to have breakthrough seizures (odds radio [OR] 3.15, P < .0001), researchers reported at the annual meeting of the American Epilepsy Society.

“If you have COVID and you have a seizure, it’s more likely that you’re having it for the first time, and it’s not as likely that you have epilepsy,” study lead author Neeraj Singh, MD, a neurologist at the New York-based Northwell Health system, said in an interview. “That’s new. We don’t normally see that when someone has a bacterial or viral infection. It’s demonstrating that this infection is having direct effect on the brain and brain signals.”

According to Dr. Singh, there’s little data about seizures in patients with COVID-19 because doctors have focused on other symptoms. A 2021 multicenter study found that electrographic seizures were detected in 9.6% of 197 patients with COVID-19 who were referred for cEEG.

For the new study, Dr. Singh and a colleague tracked 917 patients with COVID-19 in the Northwell Health system who were treated from Feb. 14 to June 14, 2020, with antiepileptic medication. Of the patients, 451 had a history of epilepsy, and 466 did not.

According to Dr. Singh, 27.6% of the patients without a history of epilepsy had new-onset seizures, while 10.1% of the patients with history of epilepsy had breakthrough seizures. The difference in odds was more than threefold after adjustment. (Among all COVID-19 patients, he said, perhaps 8%-16% had seizures).

The researchers also found that patients with new-onset seizures stayed in the hospital much longer (average, 26.9 days) than any patients with a known history of epilepsy (12.8 days, P < .0001, for those who had breakthrough seizures and 10.9 days, P < .0001, for those who didn’t).

In addition, the researchers found that having any seizures – new-onset or breakthrough – was linked to higher risk of death (OR 1.41, P = .03).

Antiseizure medications are key treatments for these patients, Dr. Singh said. As for the patients with new-onset seizures who recover from COVID-19, Dr. Singh said, “it’s suspected that these people are going to have a new diagnosis of epilepsy, not just a one-time seizure.”

The findings suggest that some patients with epilepsy are protected against COVID-19-related seizures because they take antiepileptic medications that “protect the brain from getting a trigger for an abnormal signal that leads to a seizure,” he said. “That’s one possibility.”

What can neurologists learn from the study? Dr. Singh recommends a “lower threshold” to recommend or approve EEGs in patients with COVID-19 who are confused/altered when they come in, especially if this is not normal. “They may actually be having silent seizures that no one’s noticing,” he said.

No study funding was reported. The authors reported no relevant disclosures.

Progression free survival was better at 2 years when polatuzumab-vedotin (Polivy) was added to a modified R-CHOP regimen for first-line treatment of diffuse large B-cell lymphoma (DLBCL), but there was no difference in overall survival in a phase 3 trial from maker Genentech/Roche.

Two-year progression free survival (PFS) was 76.7% for the 440 patients randomized to polatuzumab-vedotin (PV) add-on, versus 70.2% for the 439 randomized to R-CHOP, which translated to a 27% reduction in the risk of progression, relapse, or death (P = .02). However, overall survival (OS) at 2 years was just under 89% in both arms of the trial, dubbed POLARIX. Toxicity was comparable between the two arms.

The investigators swapped out the vincristine in R-CHOP for PV to avoid overlapping neurotoxic side effects and called their modified regimen “pola-R-CHP.”

“We believe these results support use of pola-R-CHP in the initial management of patients with DLBCL,” senior investigator Gilles Salles, MD, PhD, a hematologic oncologist at Memorial Sloan Cancer Center in New York, said at the American Society of Hematology annual meeting.

The study (ASH 2021 abstract LBA-1), was published simultaneously in the New England Journal of Medicine.
 

Worth the cost?

The investigators reported that the median follow up of 28.2 months may simply have been too short to see if the PFS benefit translates into better overall survival. Also, newer treatments for relapsed/refractory disease might have masked any OS benefit.

With the PFS benefit, however, “what we think we are seeing is a deeper, more profound complete remission that hopefully will translate into [better] overall survival, but it may be a while until that can be demonstrated,” said Jane N. Winter, MD, a hematologic oncologist at Northwestern University, Chicago, who moderated Dr. Salles’ presentation.

“If the improvement in PFS at 2 years represents a true higher cure rate and plateau rather than a simple delay in relapse,” the “results from the POLARIX trial are likely to be practice-changing,” blood cancer specialist Ajay K. Gopal, MD, professor of medicine at the University of Washington, Seattle, told this news organization when asked for comment.

With additional OS results pending, an audience member at ASH wondered if “the cost of this highly expensive monoclonal antibody drug conjugate is worth the small improvement in PFS.”

“We have to further study this point, but at this moment what is important is to have a treatment with better efficacy and no more toxicity” than R-CHOP, lead investigator Herve Tilly, MD, a hematologic oncologist at the University of Rouen, France, said at the meeting.

Dr. Gopal said the cost concerns are legitimate, but also pointed out that they “may be somewhat offset by the potential reduction in downstream use of expensive cellular therapies.”

The findings support his assertion. With reduced PFS, R-CHOP subjects were more likely than were pola-R-CHP subjects to go on to subsequent lines of therapy (30.3% versus 22.5%).

PV is already approved in the United States for relapsed or refractory DLBCL in combination with bendamustine and rituximab after failure of at least two previous regimens.
 

Defining a target population

R-CHOP – rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone – has been the first-line standard of care for DLBCL for 2 decades, but it cures only about 60%-70% of patients. Researchers have tried for years to improve the cure rate by adding novel agents and other means, but outcomes haven’t been clinically meaningful, the investigators explained.

Polatuzumab, the antibody component of PV, zeroes in on a ubiquitous target on mature B-cell lymphomas, delivering vedotin, a potent microtubule inhibitor, directly to tumor cells.

Study subjects were treatment naive and a median of 65 years old with intermediate-risk or high-risk DLBCL. About a third had activated B-cell–like DLBCL, and almost two-thirds had baseline International Prognostic Index (IPI) scores between 3 and 5.

Each arm of the trial underwent six treatment cycles, plus two cycles of rituximab monotherapy.

On subgroup analysis, PFS benefit clustered among higher risk patients, namely patients older than 60 years, those with IPI scores between 3 and 5, and patients with the activated B-cell–like subtype.

Younger patients, subjects with lower IPI scores, patients with bulky disease, and those who had germinal-center B-cell–like DLBCL “did not show a clear [PFS] benefit,” the study team said.
 

Ongoing trial in the elderly

Adverse events in POLARIX were in line with the component drugs’ known toxicity profiles, with no new safety signals identified.

The most common grade 3/4 adverse events were neutropenia (28.3% in the pola-R-CHP group and 30.8% in the R-CHOP group), febrile neutropenia (13.8% and 8.0%, respectively), and anemia (12.0% and 8.4%). A bit over 6% of subjects in both arms discontinued because of adverse events.

The higher incidence of febrile neutropenia with pola-R-CHP “did not translate into a higher overall incidence of infection, treatment discontinuation, or dose reductions,” the investigators said.

They noted that patients with lymphoma arising from previously diagnosed indolent lymphoma, those with a primary mediastinal lymphoma, and people older than 80 years were not included in the study. A phase 3 trial in patients 75 years and up is recruiting.

The work was funded by PV maker Genentech/Roche. Many of the investigators disclosed ties to the companies, including Dr. Tilly, an adviser and speaker for Roche, and Dr. Salles, an adviser for Genentech. Three investigators were Genentech employees. Dr. Gopal is a consultant for Genentech/Roche. Dr. Winter did not have any ties to the companies.

aotto@mdedge.com

Progression free survival was better at 2 years when polatuzumab-vedotin (Polivy) was added to a modified R-CHOP regimen for first-line treatment of diffuse large B-cell lymphoma (DLBCL), but there was no difference in overall survival in a phase 3 trial from maker Genentech/Roche.

Two-year progression free survival (PFS) was 76.7% for the 440 patients randomized to polatuzumab-vedotin (PV) add-on, versus 70.2% for the 439 randomized to R-CHOP, which translated to a 27% reduction in the risk of progression, relapse, or death (P = .02). However, overall survival (OS) at 2 years was just under 89% in both arms of the trial, dubbed POLARIX. Toxicity was comparable between the two arms.

The investigators swapped out the vincristine in R-CHOP for PV to avoid overlapping neurotoxic side effects and called their modified regimen “pola-R-CHP.”

“We believe these results support use of pola-R-CHP in the initial management of patients with DLBCL,” senior investigator Gilles Salles, MD, PhD, a hematologic oncologist at Memorial Sloan Cancer Center in New York, said at the American Society of Hematology annual meeting.

The study (ASH 2021 abstract LBA-1), was published simultaneously in the New England Journal of Medicine.
 

Worth the cost?

The investigators reported that the median follow up of 28.2 months may simply have been too short to see if the PFS benefit translates into better overall survival. Also, newer treatments for relapsed/refractory disease might have masked any OS benefit.

With the PFS benefit, however, “what we think we are seeing is a deeper, more profound complete remission that hopefully will translate into [better] overall survival, but it may be a while until that can be demonstrated,” said Jane N. Winter, MD, a hematologic oncologist at Northwestern University, Chicago, who moderated Dr. Salles’ presentation.

“If the improvement in PFS at 2 years represents a true higher cure rate and plateau rather than a simple delay in relapse,” the “results from the POLARIX trial are likely to be practice-changing,” blood cancer specialist Ajay K. Gopal, MD, professor of medicine at the University of Washington, Seattle, told this news organization when asked for comment.

With additional OS results pending, an audience member at ASH wondered if “the cost of this highly expensive monoclonal antibody drug conjugate is worth the small improvement in PFS.”

“We have to further study this point, but at this moment what is important is to have a treatment with better efficacy and no more toxicity” than R-CHOP, lead investigator Herve Tilly, MD, a hematologic oncologist at the University of Rouen, France, said at the meeting.

Dr. Gopal said the cost concerns are legitimate, but also pointed out that they “may be somewhat offset by the potential reduction in downstream use of expensive cellular therapies.”

The findings support his assertion. With reduced PFS, R-CHOP subjects were more likely than were pola-R-CHP subjects to go on to subsequent lines of therapy (30.3% versus 22.5%).

PV is already approved in the United States for relapsed or refractory DLBCL in combination with bendamustine and rituximab after failure of at least two previous regimens.
 

Defining a target population

R-CHOP – rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone – has been the first-line standard of care for DLBCL for 2 decades, but it cures only about 60%-70% of patients. Researchers have tried for years to improve the cure rate by adding novel agents and other means, but outcomes haven’t been clinically meaningful, the investigators explained.

Polatuzumab, the antibody component of PV, zeroes in on a ubiquitous target on mature B-cell lymphomas, delivering vedotin, a potent microtubule inhibitor, directly to tumor cells.

Study subjects were treatment naive and a median of 65 years old with intermediate-risk or high-risk DLBCL. About a third had activated B-cell–like DLBCL, and almost two-thirds had baseline International Prognostic Index (IPI) scores between 3 and 5.

Each arm of the trial underwent six treatment cycles, plus two cycles of rituximab monotherapy.

On subgroup analysis, PFS benefit clustered among higher risk patients, namely patients older than 60 years, those with IPI scores between 3 and 5, and patients with the activated B-cell–like subtype.

Younger patients, subjects with lower IPI scores, patients with bulky disease, and those who had germinal-center B-cell–like DLBCL “did not show a clear [PFS] benefit,” the study team said.
 

Ongoing trial in the elderly

Adverse events in POLARIX were in line with the component drugs’ known toxicity profiles, with no new safety signals identified.

The most common grade 3/4 adverse events were neutropenia (28.3% in the pola-R-CHP group and 30.8% in the R-CHOP group), febrile neutropenia (13.8% and 8.0%, respectively), and anemia (12.0% and 8.4%). A bit over 6% of subjects in both arms discontinued because of adverse events.

The higher incidence of febrile neutropenia with pola-R-CHP “did not translate into a higher overall incidence of infection, treatment discontinuation, or dose reductions,” the investigators said.

They noted that patients with lymphoma arising from previously diagnosed indolent lymphoma, those with a primary mediastinal lymphoma, and people older than 80 years were not included in the study. A phase 3 trial in patients 75 years and up is recruiting.

The work was funded by PV maker Genentech/Roche. Many of the investigators disclosed ties to the companies, including Dr. Tilly, an adviser and speaker for Roche, and Dr. Salles, an adviser for Genentech. Three investigators were Genentech employees. Dr. Gopal is a consultant for Genentech/Roche. Dr. Winter did not have any ties to the companies.

aotto@mdedge.com

Progression free survival was better at 2 years when polatuzumab-vedotin (Polivy) was added to a modified R-CHOP regimen for first-line treatment of diffuse large B-cell lymphoma (DLBCL), but there was no difference in overall survival in a phase 3 trial from maker Genentech/Roche.

Two-year progression free survival (PFS) was 76.7% for the 440 patients randomized to polatuzumab-vedotin (PV) add-on, versus 70.2% for the 439 randomized to R-CHOP, which translated to a 27% reduction in the risk of progression, relapse, or death (P = .02). However, overall survival (OS) at 2 years was just under 89% in both arms of the trial, dubbed POLARIX. Toxicity was comparable between the two arms.

The investigators swapped out the vincristine in R-CHOP for PV to avoid overlapping neurotoxic side effects and called their modified regimen “pola-R-CHP.”

“We believe these results support use of pola-R-CHP in the initial management of patients with DLBCL,” senior investigator Gilles Salles, MD, PhD, a hematologic oncologist at Memorial Sloan Cancer Center in New York, said at the American Society of Hematology annual meeting.

The study (ASH 2021 abstract LBA-1), was published simultaneously in the New England Journal of Medicine.
 

Worth the cost?

The investigators reported that the median follow up of 28.2 months may simply have been too short to see if the PFS benefit translates into better overall survival. Also, newer treatments for relapsed/refractory disease might have masked any OS benefit.

With the PFS benefit, however, “what we think we are seeing is a deeper, more profound complete remission that hopefully will translate into [better] overall survival, but it may be a while until that can be demonstrated,” said Jane N. Winter, MD, a hematologic oncologist at Northwestern University, Chicago, who moderated Dr. Salles’ presentation.

“If the improvement in PFS at 2 years represents a true higher cure rate and plateau rather than a simple delay in relapse,” the “results from the POLARIX trial are likely to be practice-changing,” blood cancer specialist Ajay K. Gopal, MD, professor of medicine at the University of Washington, Seattle, told this news organization when asked for comment.

With additional OS results pending, an audience member at ASH wondered if “the cost of this highly expensive monoclonal antibody drug conjugate is worth the small improvement in PFS.”

“We have to further study this point, but at this moment what is important is to have a treatment with better efficacy and no more toxicity” than R-CHOP, lead investigator Herve Tilly, MD, a hematologic oncologist at the University of Rouen, France, said at the meeting.

Dr. Gopal said the cost concerns are legitimate, but also pointed out that they “may be somewhat offset by the potential reduction in downstream use of expensive cellular therapies.”

The findings support his assertion. With reduced PFS, R-CHOP subjects were more likely than were pola-R-CHP subjects to go on to subsequent lines of therapy (30.3% versus 22.5%).

PV is already approved in the United States for relapsed or refractory DLBCL in combination with bendamustine and rituximab after failure of at least two previous regimens.
 

Defining a target population

R-CHOP – rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone – has been the first-line standard of care for DLBCL for 2 decades, but it cures only about 60%-70% of patients. Researchers have tried for years to improve the cure rate by adding novel agents and other means, but outcomes haven’t been clinically meaningful, the investigators explained.

Polatuzumab, the antibody component of PV, zeroes in on a ubiquitous target on mature B-cell lymphomas, delivering vedotin, a potent microtubule inhibitor, directly to tumor cells.

Study subjects were treatment naive and a median of 65 years old with intermediate-risk or high-risk DLBCL. About a third had activated B-cell–like DLBCL, and almost two-thirds had baseline International Prognostic Index (IPI) scores between 3 and 5.

Each arm of the trial underwent six treatment cycles, plus two cycles of rituximab monotherapy.

On subgroup analysis, PFS benefit clustered among higher risk patients, namely patients older than 60 years, those with IPI scores between 3 and 5, and patients with the activated B-cell–like subtype.

Younger patients, subjects with lower IPI scores, patients with bulky disease, and those who had germinal-center B-cell–like DLBCL “did not show a clear [PFS] benefit,” the study team said.
 

Ongoing trial in the elderly

Adverse events in POLARIX were in line with the component drugs’ known toxicity profiles, with no new safety signals identified.

The most common grade 3/4 adverse events were neutropenia (28.3% in the pola-R-CHP group and 30.8% in the R-CHOP group), febrile neutropenia (13.8% and 8.0%, respectively), and anemia (12.0% and 8.4%). A bit over 6% of subjects in both arms discontinued because of adverse events.

The higher incidence of febrile neutropenia with pola-R-CHP “did not translate into a higher overall incidence of infection, treatment discontinuation, or dose reductions,” the investigators said.

They noted that patients with lymphoma arising from previously diagnosed indolent lymphoma, those with a primary mediastinal lymphoma, and people older than 80 years were not included in the study. A phase 3 trial in patients 75 years and up is recruiting.

The work was funded by PV maker Genentech/Roche. Many of the investigators disclosed ties to the companies, including Dr. Tilly, an adviser and speaker for Roche, and Dr. Salles, an adviser for Genentech. Three investigators were Genentech employees. Dr. Gopal is a consultant for Genentech/Roche. Dr. Winter did not have any ties to the companies.

aotto@mdedge.com

ATLANTA – Virtual clinic visits have enabled sickle cell disease patients to stay alive and healthier during the COVID-19 pandemic, but concerns remain for those who lack access to specialized care centers, according to an investigator at the annual meeting of the American Society of Hematology.

During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.

ASH

ATLANTA – Virtual clinic visits have enabled sickle cell disease patients to stay alive and healthier during the COVID-19 pandemic, but concerns remain for those who lack access to specialized care centers, according to an investigator at the annual meeting of the American Society of Hematology.

During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.

ASH

ATLANTA – Virtual clinic visits have enabled sickle cell disease patients to stay alive and healthier during the COVID-19 pandemic, but concerns remain for those who lack access to specialized care centers, according to an investigator at the annual meeting of the American Society of Hematology.

During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.

ASH

A growing number of patients with opioid use disorder (OUD) have a diagnosis of comorbid attention-deficit/hyperactivity disorder (ADHD), raising issues about whether it’s appropriate to prescribe stimulants in this patient population.

One new study showed that from 2007-2017, there was a threefold increase in OUD and comorbid ADHD and that a significant number of these patients received prescription stimulants.

“This is the beginning stages of looking at whether or not there are risks of prescribing stimulants to patients who are on medications for opioid use disorder,” investigator Tae Woo (Ted) Park, MD, assistant professor, department of psychiatry, University of Pittsburgh School of Medicine, told this news organization.

“More and more people are being identified with ADHD, and we need to do more research on the best way to manage this patient group,” Dr. Park added.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry.
 

Biological connection?

Dr. Park is not convinced there is “an actual biological connection” between ADHD and OUD, noting that there are many reasons why patients with ADHD may be more prone to developing such a disorder.

Perhaps they did not get an ADHD diagnosis as a child, “which led to impairment in their ability to be successful at school and then in a job,” which in turn predisposed them to having a substance use disorder, said Dr. Park.

From previous research and his own clinical experience, ADHD can significantly affect quality of life and “cause increased impairment” in patients with a substance use disorder, he added.

Interestingly, there’s evidence suggesting patients treated for ADHD early in life are less likely to develop a substance use disorder later on, he said.

The “gold standard” treatment for ADHD is a prescription stimulant, which carries its own addiction risks. “So the issue is about whether or not to prescribe risky medications and how to weigh the risks and benefits,” said Dr. Park.

From a private health insurance database, researchers examined records for patients aged 18-64 years who were receiving medication for OUD, including buprenorphine, methadone, or naltrexone, from 2007-2017.

In the study sample, about 17,000 individuals were receiving stimulants, and 156,000 were not receiving these drugs. The largest percentage of participants in both groups was in the age-18-to-25 category.

About 35% of those receiving stimulants had ADHD, and about the same percentage had a mood disorder diagnosis.

Percentage of co-occurring ADHD and OUD increased from more than 4% in 2007 to more than 14% in 2017. The prevalence of stimulant use plus medication for OUD also increased during that time.

The increase in ADHD diagnoses may reflect growing identification of the condition, Dr. Park noted. As the opioid problem became more apparent and additional treatments made available, “there were more health care contacts, more assessments, and more diagnoses, including of ADHD,” he said.
 

Risks versus benefits

Stimulants may also be risky in patients with OUD. Results from another study presented at the AAAP meeting showed these drugs were associated with an increased chance of poisoning in patients receiving buprenorphine.

However, Dr. Park is skeptical the combination of stimulants and buprenorphine “leads to a biological risk of overdose.” He used a hypothetical scenario where other factors play into the connection: A patient gets a prescription stimulant, becomes addicted, then starts using street or illicit stimulants, which leads to a relapse on opioids, and then to an overdose.

Dr. Park noted that the same study that found an increased poisoning risk in stimulant users also found that patients tend to stay on buprenorphine treatment, providing protection against overdose.

“So there are risks and benefits of prescribing these medications, and it becomes tricky to know whether to prescribe them or not,” he said.

While stimulants are by far the best treatment for ADHD, atomoxetine (Strattera), a nonstimulant medication with antidepressant effects is another option, Dr. Park said.

He added that a limitation of his study was that very few individuals in the database received methadone.

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

A growing number of patients with opioid use disorder (OUD) have a diagnosis of comorbid attention-deficit/hyperactivity disorder (ADHD), raising issues about whether it’s appropriate to prescribe stimulants in this patient population.

One new study showed that from 2007-2017, there was a threefold increase in OUD and comorbid ADHD and that a significant number of these patients received prescription stimulants.

“This is the beginning stages of looking at whether or not there are risks of prescribing stimulants to patients who are on medications for opioid use disorder,” investigator Tae Woo (Ted) Park, MD, assistant professor, department of psychiatry, University of Pittsburgh School of Medicine, told this news organization.

“More and more people are being identified with ADHD, and we need to do more research on the best way to manage this patient group,” Dr. Park added.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry.
 

Biological connection?

Dr. Park is not convinced there is “an actual biological connection” between ADHD and OUD, noting that there are many reasons why patients with ADHD may be more prone to developing such a disorder.

Perhaps they did not get an ADHD diagnosis as a child, “which led to impairment in their ability to be successful at school and then in a job,” which in turn predisposed them to having a substance use disorder, said Dr. Park.

From previous research and his own clinical experience, ADHD can significantly affect quality of life and “cause increased impairment” in patients with a substance use disorder, he added.

Interestingly, there’s evidence suggesting patients treated for ADHD early in life are less likely to develop a substance use disorder later on, he said.

The “gold standard” treatment for ADHD is a prescription stimulant, which carries its own addiction risks. “So the issue is about whether or not to prescribe risky medications and how to weigh the risks and benefits,” said Dr. Park.

From a private health insurance database, researchers examined records for patients aged 18-64 years who were receiving medication for OUD, including buprenorphine, methadone, or naltrexone, from 2007-2017.

In the study sample, about 17,000 individuals were receiving stimulants, and 156,000 were not receiving these drugs. The largest percentage of participants in both groups was in the age-18-to-25 category.

About 35% of those receiving stimulants had ADHD, and about the same percentage had a mood disorder diagnosis.

Percentage of co-occurring ADHD and OUD increased from more than 4% in 2007 to more than 14% in 2017. The prevalence of stimulant use plus medication for OUD also increased during that time.

The increase in ADHD diagnoses may reflect growing identification of the condition, Dr. Park noted. As the opioid problem became more apparent and additional treatments made available, “there were more health care contacts, more assessments, and more diagnoses, including of ADHD,” he said.
 

Risks versus benefits

Stimulants may also be risky in patients with OUD. Results from another study presented at the AAAP meeting showed these drugs were associated with an increased chance of poisoning in patients receiving buprenorphine.

However, Dr. Park is skeptical the combination of stimulants and buprenorphine “leads to a biological risk of overdose.” He used a hypothetical scenario where other factors play into the connection: A patient gets a prescription stimulant, becomes addicted, then starts using street or illicit stimulants, which leads to a relapse on opioids, and then to an overdose.

Dr. Park noted that the same study that found an increased poisoning risk in stimulant users also found that patients tend to stay on buprenorphine treatment, providing protection against overdose.

“So there are risks and benefits of prescribing these medications, and it becomes tricky to know whether to prescribe them or not,” he said.

While stimulants are by far the best treatment for ADHD, atomoxetine (Strattera), a nonstimulant medication with antidepressant effects is another option, Dr. Park said.

He added that a limitation of his study was that very few individuals in the database received methadone.

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

A growing number of patients with opioid use disorder (OUD) have a diagnosis of comorbid attention-deficit/hyperactivity disorder (ADHD), raising issues about whether it’s appropriate to prescribe stimulants in this patient population.

One new study showed that from 2007-2017, there was a threefold increase in OUD and comorbid ADHD and that a significant number of these patients received prescription stimulants.

“This is the beginning stages of looking at whether or not there are risks of prescribing stimulants to patients who are on medications for opioid use disorder,” investigator Tae Woo (Ted) Park, MD, assistant professor, department of psychiatry, University of Pittsburgh School of Medicine, told this news organization.

“More and more people are being identified with ADHD, and we need to do more research on the best way to manage this patient group,” Dr. Park added.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry.
 

Biological connection?

Dr. Park is not convinced there is “an actual biological connection” between ADHD and OUD, noting that there are many reasons why patients with ADHD may be more prone to developing such a disorder.

Perhaps they did not get an ADHD diagnosis as a child, “which led to impairment in their ability to be successful at school and then in a job,” which in turn predisposed them to having a substance use disorder, said Dr. Park.

From previous research and his own clinical experience, ADHD can significantly affect quality of life and “cause increased impairment” in patients with a substance use disorder, he added.

Interestingly, there’s evidence suggesting patients treated for ADHD early in life are less likely to develop a substance use disorder later on, he said.

The “gold standard” treatment for ADHD is a prescription stimulant, which carries its own addiction risks. “So the issue is about whether or not to prescribe risky medications and how to weigh the risks and benefits,” said Dr. Park.

From a private health insurance database, researchers examined records for patients aged 18-64 years who were receiving medication for OUD, including buprenorphine, methadone, or naltrexone, from 2007-2017.

In the study sample, about 17,000 individuals were receiving stimulants, and 156,000 were not receiving these drugs. The largest percentage of participants in both groups was in the age-18-to-25 category.

About 35% of those receiving stimulants had ADHD, and about the same percentage had a mood disorder diagnosis.

Percentage of co-occurring ADHD and OUD increased from more than 4% in 2007 to more than 14% in 2017. The prevalence of stimulant use plus medication for OUD also increased during that time.

The increase in ADHD diagnoses may reflect growing identification of the condition, Dr. Park noted. As the opioid problem became more apparent and additional treatments made available, “there were more health care contacts, more assessments, and more diagnoses, including of ADHD,” he said.
 

Risks versus benefits

Stimulants may also be risky in patients with OUD. Results from another study presented at the AAAP meeting showed these drugs were associated with an increased chance of poisoning in patients receiving buprenorphine.

However, Dr. Park is skeptical the combination of stimulants and buprenorphine “leads to a biological risk of overdose.” He used a hypothetical scenario where other factors play into the connection: A patient gets a prescription stimulant, becomes addicted, then starts using street or illicit stimulants, which leads to a relapse on opioids, and then to an overdose.

Dr. Park noted that the same study that found an increased poisoning risk in stimulant users also found that patients tend to stay on buprenorphine treatment, providing protection against overdose.

“So there are risks and benefits of prescribing these medications, and it becomes tricky to know whether to prescribe them or not,” he said.

While stimulants are by far the best treatment for ADHD, atomoxetine (Strattera), a nonstimulant medication with antidepressant effects is another option, Dr. Park said.

He added that a limitation of his study was that very few individuals in the database received methadone.

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