MDedge Neurology

While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.

In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”

In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.

“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”

Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”

Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.

In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.

In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.

Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.

The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.

“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted. 
 

More data with more study designs

Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.

“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.

Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.

With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.

“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”

For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.

It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.

“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”

Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
 

‘A lot of redundancy’

Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.

“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.

“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”

Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.

The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.

“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”

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

While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.

In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”

In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.

“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”

Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”

Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.

In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.

In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.

Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.

The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.

“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted. 
 

More data with more study designs

Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.

“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.

Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.

With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.

“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”

For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.

It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.

“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”

Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
 

‘A lot of redundancy’

Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.

“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.

“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”

Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.

The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.

“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”

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

While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.

In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”

In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.

“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”

Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”

Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.

In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.

In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.

Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.

The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.

“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted. 
 

More data with more study designs

Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.

“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.

Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.

With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.

“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”

For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.

It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.

“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”

Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
 

‘A lot of redundancy’

Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.

“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.

“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”

Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.

The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.

“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”

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

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

Medication overuse headache presents difficult challenges for both patients and physicians. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.

These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.

The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.

Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
 

Is medication overuse really the culprit?

Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.

Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.

He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.

Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.

Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.

“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.

A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.

He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”

To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.

He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
 

Medication overuse is to blame

Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.

Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.

She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.

Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.

Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.

These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.

Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.

Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
 

Common ground

Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.

In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.

In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.

“I absolutely agree with that,” responded Dr. Nye.

Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.

Medication overuse headache presents difficult challenges for both patients and physicians. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.

These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.

The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.

Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
 

Is medication overuse really the culprit?

Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.

Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.

He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.

Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.

Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.

“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.

A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.

He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”

To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.

He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
 

Medication overuse is to blame

Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.

Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.

She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.

Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.

Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.

These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.

Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.

Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
 

Common ground

Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.

In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.

In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.

“I absolutely agree with that,” responded Dr. Nye.

Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.

Medication overuse headache presents difficult challenges for both patients and physicians. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.

These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.

The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.

Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
 

Is medication overuse really the culprit?

Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.

Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.

He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.

Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.

Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.

“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.

A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.

He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”

To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.

He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
 

Medication overuse is to blame

Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.

Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.

She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.

Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.

Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.

These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.

Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.

Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
 

Common ground

Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.

In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.

In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.

“I absolutely agree with that,” responded Dr. Nye.

Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Contrary to historical evidence, among older people, elevated LDL cholesterol levels increase risk for heart attack and cardiovascular disease, and older patients benefit as much, if not more, from statins and other cholesterol-lowering drugs than do younger people, two new studies show.

“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.

“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.

“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).

The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.

“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.

“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
 

No RCTs have included patients older than 70

For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.

However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.

Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.

As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
 

Primary prevention: CV events increase with elevated LDL cholesterol in older age

Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.

Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.

Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.

In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).

Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.

Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).

The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.

“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.

With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.

With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.

“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”

“These robust findings are novel,” he and his colleagues stressed.

Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.

The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
 

Unequivocal reductions in events in elderly, comparable with younger patients

In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.

The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.

The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.

The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).

Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).

“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.

“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.

“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”

The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”

The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.

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

Contrary to historical evidence, among older people, elevated LDL cholesterol levels increase risk for heart attack and cardiovascular disease, and older patients benefit as much, if not more, from statins and other cholesterol-lowering drugs than do younger people, two new studies show.

“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.

“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.

“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).

The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.

“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.

“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
 

No RCTs have included patients older than 70

For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.

However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.

Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.

As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
 

Primary prevention: CV events increase with elevated LDL cholesterol in older age

Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.

Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.

Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.

In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).

Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.

Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).

The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.

“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.

With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.

With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.

“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”

“These robust findings are novel,” he and his colleagues stressed.

Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.

The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
 

Unequivocal reductions in events in elderly, comparable with younger patients

In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.

The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.

The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.

The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).

Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).

“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.

“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.

“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”

The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”

The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.

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

Contrary to historical evidence, among older people, elevated LDL cholesterol levels increase risk for heart attack and cardiovascular disease, and older patients benefit as much, if not more, from statins and other cholesterol-lowering drugs than do younger people, two new studies show.

“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.

“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.

“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).

The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.

“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.

“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
 

No RCTs have included patients older than 70

For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.

However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.

Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.

As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
 

Primary prevention: CV events increase with elevated LDL cholesterol in older age

Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.

Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.

Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.

In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).

Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.

Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).

The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.

“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.

With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.

With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.

“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”

“These robust findings are novel,” he and his colleagues stressed.

Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.

The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
 

Unequivocal reductions in events in elderly, comparable with younger patients

In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.

The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.

The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.

The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).

Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).

“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.

“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.

“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”

The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”

The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.

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

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

rfranki@mdedge.com

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

rfranki@mdedge.com

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

rfranki@mdedge.com

Concussion is associated with increased risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD), as well as dementia and Parkinson’s disease, new research suggests. Results from a retrospective, population-based cohort study showed that controlling for socioeconomic status and overall health did not significantly affect this association.

The link between concussion and risk for ADHD and for mood and anxiety disorder was stronger in the women than in the men. In addition, having a history of multiple concussions strengthened the association between concussion and subsequent mood and anxiety disorder, dementia, and Parkinson’s disease compared with experiencing just one concussion.

The findings are similar to those of previous studies, noted lead author Marc P. Morissette, PhD, research assistant at the Pan Am Clinic Foundation in Winnipeg, Manitoba, Canada. “The main methodological differences separating our study from previous studies in this area is a focus on concussion-specific injuries identified from medical records and the potential for study participants to have up to 25 years of follow-up data,” said Dr. Morissette.

The findings were published online July 27 in Family Medicine and Community Health, a BMJ journal.
 

Almost 190,000 participants

Several studies have shown associations between head injury and increased risk for ADHD, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease. However, many of these studies relied on self-reported medical history, included all forms of traumatic brain injury, and failed to adjust for preexisting health conditions.

An improved understanding of concussion and the risks associated with it could help physicians manage their patients’ long-term needs, the investigators noted.

In the current study, the researchers examined anonymized administrative health data collected between the periods of 1990–1991 and 2014–2015 in the Manitoba Population Research Data Repository at the Manitoba Center for Health Policy.

Eligible patients had been diagnosed with concussion in accordance with standard criteria. Participants were excluded if they had been diagnosed with dementia or Parkinson’s disease before the incident concussion during the study period. The investigators matched three control participants to each included patient on the basis of age, sex, and location.

Study outcome was time from index date (date of first concussion) to diagnosis of ADHD, mood and anxiety disorder, dementia, or Parkinson’s disease. The researchers controlled for socioeconomic status using the Socioeconomic Factor Index, version 2 (SEFI2), and for preexisting medical conditions using the Charlson Comorbidity Index (CCI).

The study included 28,021 men (mean age, 25 years) and 19,462 women (mean age, 30 years) in the concussion group and 81,871 men (mean age, 25 years) and 57,159 women (mean age, 30 years) in the control group. Mean SEFI2 score was approximately −0.05, and mean CCI score was approximately 0.2.
 

Dose effect?

Results showed that concussion was associated with an increased risk for ADHD (hazard ratio [HR], 1.39), mood and anxiety disorder (HR, 1.72), dementia (HR, 1.72), and Parkinson’s disease (HR, 1.57).

After a concussion, the risk of developing ADHD was 28% higher and the risk of developing mood and anxiety disorder was 7% higher among women than among men. Gender was not associated with risk for dementia or Parkinson’s disease after concussion.

Sustaining a second concussion increased the strength of the association with risk for dementia compared with sustaining a single concussion (HR, 1.62). Similarly, sustaining more than three concussions increased the strength of the association with the risk for mood and anxiety disorders (HR for more than three vs one concussion, 1.22) and Parkinson›s disease (HR, 3.27).

A sensitivity analysis found similar associations between concussion and risk for mood and anxiety disorder among all age groups. Younger participants were at greater risk for ADHD, however, and older participants were at greater risk for dementia and Parkinson’s disease.

Increased awareness of concussion and the outcomes of interest, along with improved diagnostic tools, may have influenced the study’s findings, Dr. Morissette noted. “The sex-based differences may be due to either pathophysiological differences in response to concussive injuries or potentially a difference in willingness to seek medical care or share symptoms, concussion-related or otherwise, with a medical professional,” he said.

“We are hopeful that our findings will encourage practitioners to be cognizant of various conditions that may present in individuals who have previously experienced a concussion,” Dr. Morissette added. “If physicians are aware of the various associations identified following a concussion, it may lead to more thorough clinical examination at initial presentation, along with more dedicated care throughout the patient’s life.”
 

Association versus causation

Commenting on the research, Steven Erickson, MD, sports medicine specialist at Banner–University Medicine Neuroscience Institute, Phoenix, Ariz., noted that although the study showed an association between concussion and subsequent diagnosis of ADHD, anxiety, and Parkinson’s disease, “this association should not be misconstrued as causation.” He added that the study’s conclusions “are just as likely to be due to labeling theory” or a self-fulfilling prophecy.

“Patients diagnosed with ADHD, anxiety, or Parkinson’s disease may recall concussion and associate the two diagnoses; but patients who have not previously been diagnosed with a concussion cannot draw that conclusion,” said Dr. Erickson, who was not involved with the research.

Citing the apparent gender difference in the strength of the association between concussion and the outcomes of interest, Dr. Erickson noted that women are more likely to report symptoms in general “and therefore are more likely to be diagnosed with ADHD and anxiety disorders” because of differences in reporting rather than incidence of disease.

“Further research needs to be done to definitively determine a causal relationship between concussion and any psychiatric or neurologic diagnosis,” Dr. Erickson concluded.

The study was funded by the Pan Am Clinic Foundation. Dr. Morissette and Dr. Erickson have disclosed no relevant financial relationships.

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

Concussion is associated with increased risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD), as well as dementia and Parkinson’s disease, new research suggests. Results from a retrospective, population-based cohort study showed that controlling for socioeconomic status and overall health did not significantly affect this association.

The link between concussion and risk for ADHD and for mood and anxiety disorder was stronger in the women than in the men. In addition, having a history of multiple concussions strengthened the association between concussion and subsequent mood and anxiety disorder, dementia, and Parkinson’s disease compared with experiencing just one concussion.

The findings are similar to those of previous studies, noted lead author Marc P. Morissette, PhD, research assistant at the Pan Am Clinic Foundation in Winnipeg, Manitoba, Canada. “The main methodological differences separating our study from previous studies in this area is a focus on concussion-specific injuries identified from medical records and the potential for study participants to have up to 25 years of follow-up data,” said Dr. Morissette.

The findings were published online July 27 in Family Medicine and Community Health, a BMJ journal.
 

Almost 190,000 participants

Several studies have shown associations between head injury and increased risk for ADHD, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease. However, many of these studies relied on self-reported medical history, included all forms of traumatic brain injury, and failed to adjust for preexisting health conditions.

An improved understanding of concussion and the risks associated with it could help physicians manage their patients’ long-term needs, the investigators noted.

In the current study, the researchers examined anonymized administrative health data collected between the periods of 1990–1991 and 2014–2015 in the Manitoba Population Research Data Repository at the Manitoba Center for Health Policy.

Eligible patients had been diagnosed with concussion in accordance with standard criteria. Participants were excluded if they had been diagnosed with dementia or Parkinson’s disease before the incident concussion during the study period. The investigators matched three control participants to each included patient on the basis of age, sex, and location.

Study outcome was time from index date (date of first concussion) to diagnosis of ADHD, mood and anxiety disorder, dementia, or Parkinson’s disease. The researchers controlled for socioeconomic status using the Socioeconomic Factor Index, version 2 (SEFI2), and for preexisting medical conditions using the Charlson Comorbidity Index (CCI).

The study included 28,021 men (mean age, 25 years) and 19,462 women (mean age, 30 years) in the concussion group and 81,871 men (mean age, 25 years) and 57,159 women (mean age, 30 years) in the control group. Mean SEFI2 score was approximately −0.05, and mean CCI score was approximately 0.2.
 

Dose effect?

Results showed that concussion was associated with an increased risk for ADHD (hazard ratio [HR], 1.39), mood and anxiety disorder (HR, 1.72), dementia (HR, 1.72), and Parkinson’s disease (HR, 1.57).

After a concussion, the risk of developing ADHD was 28% higher and the risk of developing mood and anxiety disorder was 7% higher among women than among men. Gender was not associated with risk for dementia or Parkinson’s disease after concussion.

Sustaining a second concussion increased the strength of the association with risk for dementia compared with sustaining a single concussion (HR, 1.62). Similarly, sustaining more than three concussions increased the strength of the association with the risk for mood and anxiety disorders (HR for more than three vs one concussion, 1.22) and Parkinson›s disease (HR, 3.27).

A sensitivity analysis found similar associations between concussion and risk for mood and anxiety disorder among all age groups. Younger participants were at greater risk for ADHD, however, and older participants were at greater risk for dementia and Parkinson’s disease.

Increased awareness of concussion and the outcomes of interest, along with improved diagnostic tools, may have influenced the study’s findings, Dr. Morissette noted. “The sex-based differences may be due to either pathophysiological differences in response to concussive injuries or potentially a difference in willingness to seek medical care or share symptoms, concussion-related or otherwise, with a medical professional,” he said.

“We are hopeful that our findings will encourage practitioners to be cognizant of various conditions that may present in individuals who have previously experienced a concussion,” Dr. Morissette added. “If physicians are aware of the various associations identified following a concussion, it may lead to more thorough clinical examination at initial presentation, along with more dedicated care throughout the patient’s life.”
 

Association versus causation

Commenting on the research, Steven Erickson, MD, sports medicine specialist at Banner–University Medicine Neuroscience Institute, Phoenix, Ariz., noted that although the study showed an association between concussion and subsequent diagnosis of ADHD, anxiety, and Parkinson’s disease, “this association should not be misconstrued as causation.” He added that the study’s conclusions “are just as likely to be due to labeling theory” or a self-fulfilling prophecy.

“Patients diagnosed with ADHD, anxiety, or Parkinson’s disease may recall concussion and associate the two diagnoses; but patients who have not previously been diagnosed with a concussion cannot draw that conclusion,” said Dr. Erickson, who was not involved with the research.

Citing the apparent gender difference in the strength of the association between concussion and the outcomes of interest, Dr. Erickson noted that women are more likely to report symptoms in general “and therefore are more likely to be diagnosed with ADHD and anxiety disorders” because of differences in reporting rather than incidence of disease.

“Further research needs to be done to definitively determine a causal relationship between concussion and any psychiatric or neurologic diagnosis,” Dr. Erickson concluded.

The study was funded by the Pan Am Clinic Foundation. Dr. Morissette and Dr. Erickson have disclosed no relevant financial relationships.

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

Concussion is associated with increased risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD), as well as dementia and Parkinson’s disease, new research suggests. Results from a retrospective, population-based cohort study showed that controlling for socioeconomic status and overall health did not significantly affect this association.

The link between concussion and risk for ADHD and for mood and anxiety disorder was stronger in the women than in the men. In addition, having a history of multiple concussions strengthened the association between concussion and subsequent mood and anxiety disorder, dementia, and Parkinson’s disease compared with experiencing just one concussion.

The findings are similar to those of previous studies, noted lead author Marc P. Morissette, PhD, research assistant at the Pan Am Clinic Foundation in Winnipeg, Manitoba, Canada. “The main methodological differences separating our study from previous studies in this area is a focus on concussion-specific injuries identified from medical records and the potential for study participants to have up to 25 years of follow-up data,” said Dr. Morissette.

The findings were published online July 27 in Family Medicine and Community Health, a BMJ journal.
 

Almost 190,000 participants

Several studies have shown associations between head injury and increased risk for ADHD, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease. However, many of these studies relied on self-reported medical history, included all forms of traumatic brain injury, and failed to adjust for preexisting health conditions.

An improved understanding of concussion and the risks associated with it could help physicians manage their patients’ long-term needs, the investigators noted.

In the current study, the researchers examined anonymized administrative health data collected between the periods of 1990–1991 and 2014–2015 in the Manitoba Population Research Data Repository at the Manitoba Center for Health Policy.

Eligible patients had been diagnosed with concussion in accordance with standard criteria. Participants were excluded if they had been diagnosed with dementia or Parkinson’s disease before the incident concussion during the study period. The investigators matched three control participants to each included patient on the basis of age, sex, and location.

Study outcome was time from index date (date of first concussion) to diagnosis of ADHD, mood and anxiety disorder, dementia, or Parkinson’s disease. The researchers controlled for socioeconomic status using the Socioeconomic Factor Index, version 2 (SEFI2), and for preexisting medical conditions using the Charlson Comorbidity Index (CCI).

The study included 28,021 men (mean age, 25 years) and 19,462 women (mean age, 30 years) in the concussion group and 81,871 men (mean age, 25 years) and 57,159 women (mean age, 30 years) in the control group. Mean SEFI2 score was approximately −0.05, and mean CCI score was approximately 0.2.
 

Dose effect?

Results showed that concussion was associated with an increased risk for ADHD (hazard ratio [HR], 1.39), mood and anxiety disorder (HR, 1.72), dementia (HR, 1.72), and Parkinson’s disease (HR, 1.57).

After a concussion, the risk of developing ADHD was 28% higher and the risk of developing mood and anxiety disorder was 7% higher among women than among men. Gender was not associated with risk for dementia or Parkinson’s disease after concussion.

Sustaining a second concussion increased the strength of the association with risk for dementia compared with sustaining a single concussion (HR, 1.62). Similarly, sustaining more than three concussions increased the strength of the association with the risk for mood and anxiety disorders (HR for more than three vs one concussion, 1.22) and Parkinson›s disease (HR, 3.27).

A sensitivity analysis found similar associations between concussion and risk for mood and anxiety disorder among all age groups. Younger participants were at greater risk for ADHD, however, and older participants were at greater risk for dementia and Parkinson’s disease.

Increased awareness of concussion and the outcomes of interest, along with improved diagnostic tools, may have influenced the study’s findings, Dr. Morissette noted. “The sex-based differences may be due to either pathophysiological differences in response to concussive injuries or potentially a difference in willingness to seek medical care or share symptoms, concussion-related or otherwise, with a medical professional,” he said.

“We are hopeful that our findings will encourage practitioners to be cognizant of various conditions that may present in individuals who have previously experienced a concussion,” Dr. Morissette added. “If physicians are aware of the various associations identified following a concussion, it may lead to more thorough clinical examination at initial presentation, along with more dedicated care throughout the patient’s life.”
 

Association versus causation

Commenting on the research, Steven Erickson, MD, sports medicine specialist at Banner–University Medicine Neuroscience Institute, Phoenix, Ariz., noted that although the study showed an association between concussion and subsequent diagnosis of ADHD, anxiety, and Parkinson’s disease, “this association should not be misconstrued as causation.” He added that the study’s conclusions “are just as likely to be due to labeling theory” or a self-fulfilling prophecy.

“Patients diagnosed with ADHD, anxiety, or Parkinson’s disease may recall concussion and associate the two diagnoses; but patients who have not previously been diagnosed with a concussion cannot draw that conclusion,” said Dr. Erickson, who was not involved with the research.

Citing the apparent gender difference in the strength of the association between concussion and the outcomes of interest, Dr. Erickson noted that women are more likely to report symptoms in general “and therefore are more likely to be diagnosed with ADHD and anxiety disorders” because of differences in reporting rather than incidence of disease.

“Further research needs to be done to definitively determine a causal relationship between concussion and any psychiatric or neurologic diagnosis,” Dr. Erickson concluded.

The study was funded by the Pan Am Clinic Foundation. Dr. Morissette and Dr. Erickson have disclosed no relevant financial relationships.

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

The American Medical Association House of Delegates has adopted a policy to educate physicians on how to speak with patients about COVID-19 vaccination to counteract widespread misinformation about the vaccine development process.

Other highlights of the AMA’s recent special meeting include a new policy on the ethics of physicians getting immunized against COVID-19 and a far-reaching statement about racism.

Under the organization’s new vaccination education policy, the AMA will provide physicians with “culturally appropriate patient education materials,” according to a news release.

This campaign will be conducted “bearing in mind the historical context of ‘experimentation’ with vaccines and other medication in communities of color,” the AMA said, apparently alluding to the infamous Tuskegee study of syphilis in Black men.

Educating the public about the safety and efficacy of the COVID-19 vaccine programs is an “urgent priority,” the AMA said. This is especially true among populations that have been disproportionately affected by the disease. Black and Latino people are being hospitalized for COVID-19 at far higher rates than White Americans.

“Under the new policy, the AMA will help address patient concerns, dispel misinformation, and build confidence in COVID-19 vaccination,” the release states. The AMA also plans to build a coalition of health care and public health organizations to develop and implement a joint public education program.

Polls have indicated that many people will not get vaccinated when supplies of the new COVID-19 vaccines are available, although public support is rising. A recent Gallup poll found that 58% of surveyed adults were willing to be inoculated, up from 50% in September.

A Kaiser Family Foundation survey in September found that a majority of Americans were skeptical of a rushed vaccine, because they were concerned that the Trump administration was pressuring the Food and Drug Administration to approve a vaccine before the election.

“Given the unprecedented situation with COVID-19 and with vaccine development moving at a rapid pace, many of our patients and the public have questions and concerns,” said AMA President Susan R. Bailey, MD, in the release. “It is essential that we speak together as a strong, unified voice across health care and public health, inclusive of organizations respected in communities of color; to use scientific, fact-based evidence to help allay public concerns; and build confidence in COVID-19 vaccine candidates that are determined to be safe and effective.”
 

Physician, immunize thyself

The AMA also adopted a new ethics policy about physician immunization. On Monday, the AMA House of Delegates stated that physicians who are not immunized from a vaccine-preventable disease have an ethical responsibility to take appropriate actions to protect patients and colleagues.

The AMA code of ethics has long maintained that physicians have a strong ethical duty to accept immunizations when a safe, effective vaccine is available. However, the organization said in a news release, “it is not ethically problematic to exempt individuals when a specific vaccine poses a risk due to underlying medical conditions.”

Ethical concerns arise when physicians are allowed to decline vaccinations for nonmedical reasons, according to a report presented to the House of Delegates by the AMA Council on Ethical and Judicial Affairs.

According to the newly amended AMA ethical guidance, “physicians who are not or cannot be immunized have a responsibility to voluntarily take appropriate actions to protect patients, fellow health care workers and others.” This includes refraining from direct patient contact.

The delegates also approved a guidance asserting that physician practices and health care institutions are responsible for developing policies and procedures for responding to pandemics and epidemics. These policies and procedures should outline appropriate protective equipment allocation, staff immunization programs, and infection control practices.
 

Combating systemic racism

In an effort to reduce racial disparities in healthcare, the AMA House of Delegates adopted new policies recognizing race as a social construct, rather than a biological construct.

“The policies aim to advance data-driven, antiracist concepts challenging the current clinical application of race and its effects on vulnerable patient populations,” an AMA statement said.

The new AMA policies “reflect an understanding of race as a socially constructed category different from ethnicity, genetic ancestry, or biology, and aim to end the misinterpretation of race as a biological category defined by genetic traits or biological differences,” the AMA said.

According to the AMA, the practice of accepting race as a biological construct “exacerbates health disparities and results in detrimental health outcomes for marginalized and minoritized communities.”

Specifically, the AMA said it supports ending the practice of using race as a proxy for biology in medical education, research, and clinical practice. It also encourages medical education programs to recognize the harmful effects of this approach. It recommends that clinicians and researchers focus on genetics and biology, the experience of racism, and social determinants of health when describing risk factors for disease.

“The AMA is dedicated to dismantling racist and discriminatory policies and practices across all of health care, and that includes the way we define race in medicine,” said AMA board member Michael Suk, MD, in its statement. “We believe it is not sufficient for medicine to be nonracist, which is why the AMA is committed to pushing for a shift in thinking from race as a biological risk factor to a deeper understanding of racism as a determinant of health.”

The AMA also plans to partner with physician organizations and other stakeholders “to identify any problematic aspects of medical education that may perpetuate institutional and structural racism.” For example, the AMA will work with other organizations to improve clinical algorithms that incorrectly adjust for race and lead to less-than-optimal care for minority patients.

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

The American Medical Association House of Delegates has adopted a policy to educate physicians on how to speak with patients about COVID-19 vaccination to counteract widespread misinformation about the vaccine development process.

Other highlights of the AMA’s recent special meeting include a new policy on the ethics of physicians getting immunized against COVID-19 and a far-reaching statement about racism.

Under the organization’s new vaccination education policy, the AMA will provide physicians with “culturally appropriate patient education materials,” according to a news release.

This campaign will be conducted “bearing in mind the historical context of ‘experimentation’ with vaccines and other medication in communities of color,” the AMA said, apparently alluding to the infamous Tuskegee study of syphilis in Black men.

Educating the public about the safety and efficacy of the COVID-19 vaccine programs is an “urgent priority,” the AMA said. This is especially true among populations that have been disproportionately affected by the disease. Black and Latino people are being hospitalized for COVID-19 at far higher rates than White Americans.

“Under the new policy, the AMA will help address patient concerns, dispel misinformation, and build confidence in COVID-19 vaccination,” the release states. The AMA also plans to build a coalition of health care and public health organizations to develop and implement a joint public education program.

Polls have indicated that many people will not get vaccinated when supplies of the new COVID-19 vaccines are available, although public support is rising. A recent Gallup poll found that 58% of surveyed adults were willing to be inoculated, up from 50% in September.

A Kaiser Family Foundation survey in September found that a majority of Americans were skeptical of a rushed vaccine, because they were concerned that the Trump administration was pressuring the Food and Drug Administration to approve a vaccine before the election.

“Given the unprecedented situation with COVID-19 and with vaccine development moving at a rapid pace, many of our patients and the public have questions and concerns,” said AMA President Susan R. Bailey, MD, in the release. “It is essential that we speak together as a strong, unified voice across health care and public health, inclusive of organizations respected in communities of color; to use scientific, fact-based evidence to help allay public concerns; and build confidence in COVID-19 vaccine candidates that are determined to be safe and effective.”
 

Physician, immunize thyself

The AMA also adopted a new ethics policy about physician immunization. On Monday, the AMA House of Delegates stated that physicians who are not immunized from a vaccine-preventable disease have an ethical responsibility to take appropriate actions to protect patients and colleagues.

The AMA code of ethics has long maintained that physicians have a strong ethical duty to accept immunizations when a safe, effective vaccine is available. However, the organization said in a news release, “it is not ethically problematic to exempt individuals when a specific vaccine poses a risk due to underlying medical conditions.”

Ethical concerns arise when physicians are allowed to decline vaccinations for nonmedical reasons, according to a report presented to the House of Delegates by the AMA Council on Ethical and Judicial Affairs.

According to the newly amended AMA ethical guidance, “physicians who are not or cannot be immunized have a responsibility to voluntarily take appropriate actions to protect patients, fellow health care workers and others.” This includes refraining from direct patient contact.

The delegates also approved a guidance asserting that physician practices and health care institutions are responsible for developing policies and procedures for responding to pandemics and epidemics. These policies and procedures should outline appropriate protective equipment allocation, staff immunization programs, and infection control practices.
 

Combating systemic racism

In an effort to reduce racial disparities in healthcare, the AMA House of Delegates adopted new policies recognizing race as a social construct, rather than a biological construct.

“The policies aim to advance data-driven, antiracist concepts challenging the current clinical application of race and its effects on vulnerable patient populations,” an AMA statement said.

The new AMA policies “reflect an understanding of race as a socially constructed category different from ethnicity, genetic ancestry, or biology, and aim to end the misinterpretation of race as a biological category defined by genetic traits or biological differences,” the AMA said.

According to the AMA, the practice of accepting race as a biological construct “exacerbates health disparities and results in detrimental health outcomes for marginalized and minoritized communities.”

Specifically, the AMA said it supports ending the practice of using race as a proxy for biology in medical education, research, and clinical practice. It also encourages medical education programs to recognize the harmful effects of this approach. It recommends that clinicians and researchers focus on genetics and biology, the experience of racism, and social determinants of health when describing risk factors for disease.

“The AMA is dedicated to dismantling racist and discriminatory policies and practices across all of health care, and that includes the way we define race in medicine,” said AMA board member Michael Suk, MD, in its statement. “We believe it is not sufficient for medicine to be nonracist, which is why the AMA is committed to pushing for a shift in thinking from race as a biological risk factor to a deeper understanding of racism as a determinant of health.”

The AMA also plans to partner with physician organizations and other stakeholders “to identify any problematic aspects of medical education that may perpetuate institutional and structural racism.” For example, the AMA will work with other organizations to improve clinical algorithms that incorrectly adjust for race and lead to less-than-optimal care for minority patients.

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

The American Medical Association House of Delegates has adopted a policy to educate physicians on how to speak with patients about COVID-19 vaccination to counteract widespread misinformation about the vaccine development process.

Other highlights of the AMA’s recent special meeting include a new policy on the ethics of physicians getting immunized against COVID-19 and a far-reaching statement about racism.

Under the organization’s new vaccination education policy, the AMA will provide physicians with “culturally appropriate patient education materials,” according to a news release.

This campaign will be conducted “bearing in mind the historical context of ‘experimentation’ with vaccines and other medication in communities of color,” the AMA said, apparently alluding to the infamous Tuskegee study of syphilis in Black men.

Educating the public about the safety and efficacy of the COVID-19 vaccine programs is an “urgent priority,” the AMA said. This is especially true among populations that have been disproportionately affected by the disease. Black and Latino people are being hospitalized for COVID-19 at far higher rates than White Americans.

“Under the new policy, the AMA will help address patient concerns, dispel misinformation, and build confidence in COVID-19 vaccination,” the release states. The AMA also plans to build a coalition of health care and public health organizations to develop and implement a joint public education program.

Polls have indicated that many people will not get vaccinated when supplies of the new COVID-19 vaccines are available, although public support is rising. A recent Gallup poll found that 58% of surveyed adults were willing to be inoculated, up from 50% in September.

A Kaiser Family Foundation survey in September found that a majority of Americans were skeptical of a rushed vaccine, because they were concerned that the Trump administration was pressuring the Food and Drug Administration to approve a vaccine before the election.

“Given the unprecedented situation with COVID-19 and with vaccine development moving at a rapid pace, many of our patients and the public have questions and concerns,” said AMA President Susan R. Bailey, MD, in the release. “It is essential that we speak together as a strong, unified voice across health care and public health, inclusive of organizations respected in communities of color; to use scientific, fact-based evidence to help allay public concerns; and build confidence in COVID-19 vaccine candidates that are determined to be safe and effective.”
 

Physician, immunize thyself

The AMA also adopted a new ethics policy about physician immunization. On Monday, the AMA House of Delegates stated that physicians who are not immunized from a vaccine-preventable disease have an ethical responsibility to take appropriate actions to protect patients and colleagues.

The AMA code of ethics has long maintained that physicians have a strong ethical duty to accept immunizations when a safe, effective vaccine is available. However, the organization said in a news release, “it is not ethically problematic to exempt individuals when a specific vaccine poses a risk due to underlying medical conditions.”

Ethical concerns arise when physicians are allowed to decline vaccinations for nonmedical reasons, according to a report presented to the House of Delegates by the AMA Council on Ethical and Judicial Affairs.

According to the newly amended AMA ethical guidance, “physicians who are not or cannot be immunized have a responsibility to voluntarily take appropriate actions to protect patients, fellow health care workers and others.” This includes refraining from direct patient contact.

The delegates also approved a guidance asserting that physician practices and health care institutions are responsible for developing policies and procedures for responding to pandemics and epidemics. These policies and procedures should outline appropriate protective equipment allocation, staff immunization programs, and infection control practices.
 

Combating systemic racism

In an effort to reduce racial disparities in healthcare, the AMA House of Delegates adopted new policies recognizing race as a social construct, rather than a biological construct.

“The policies aim to advance data-driven, antiracist concepts challenging the current clinical application of race and its effects on vulnerable patient populations,” an AMA statement said.

The new AMA policies “reflect an understanding of race as a socially constructed category different from ethnicity, genetic ancestry, or biology, and aim to end the misinterpretation of race as a biological category defined by genetic traits or biological differences,” the AMA said.

According to the AMA, the practice of accepting race as a biological construct “exacerbates health disparities and results in detrimental health outcomes for marginalized and minoritized communities.”

Specifically, the AMA said it supports ending the practice of using race as a proxy for biology in medical education, research, and clinical practice. It also encourages medical education programs to recognize the harmful effects of this approach. It recommends that clinicians and researchers focus on genetics and biology, the experience of racism, and social determinants of health when describing risk factors for disease.

“The AMA is dedicated to dismantling racist and discriminatory policies and practices across all of health care, and that includes the way we define race in medicine,” said AMA board member Michael Suk, MD, in its statement. “We believe it is not sufficient for medicine to be nonracist, which is why the AMA is committed to pushing for a shift in thinking from race as a biological risk factor to a deeper understanding of racism as a determinant of health.”

The AMA also plans to partner with physician organizations and other stakeholders “to identify any problematic aspects of medical education that may perpetuate institutional and structural racism.” For example, the AMA will work with other organizations to improve clinical algorithms that incorrectly adjust for race and lead to less-than-optimal care for minority patients.

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