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Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.

“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.

“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.

Additional research may also reveal devices or therapies that can adjust the brain signals to lower blood sugar and improve memory, the researchers say.

The study was published online August 11 in Nature.

It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.

In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.

“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.

These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.

As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.

“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.

Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.

The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.

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

Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.

“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.

“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.

Additional research may also reveal devices or therapies that can adjust the brain signals to lower blood sugar and improve memory, the researchers say.

The study was published online August 11 in Nature.

It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.

In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.

“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.

These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.

As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.

“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.

Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.

The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.

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

Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.

“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.

“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.

Additional research may also reveal devices or therapies that can adjust the brain signals to lower blood sugar and improve memory, the researchers say.

The study was published online August 11 in Nature.

It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.

In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.

“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.

These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.

As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.

“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.

Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.

The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Case vignette: Laura is a 14-year-old biological girl who presents to your office for a routine well-child visit. She is doing well medically but notes that over the past 3 months she has been having increasing thoughts of suicide and has self-harmed via cutting on her wrists with a blade removed from a shaving razor. You contemplate what the most salient questions are in order to determine the best disposition for your patient.

The case vignette above may sound like one that you have heard before, and if not, you undoubtedly will encounter such a situation moving forward. The rate of suicidal ideation amongst youth ages 10-24 has increased by 57.4% between 2007 and 2018.¹ Furthermore, suicide is the second leading cause of death in those aged 10 through young adulthood.² According to the Centers for Disease Control and Prevention’s 2019 High School Youth Risk Behavior Survey, 18.8% of high school students seriously considered attempting suicide, 15.7% made a plan about how they would attempt suicide, and 8.9% actually attempted suicide, with 2.5% having a suicide attempt that resulted in an injury, poisoning, or overdose that had to be treated by a doctor or nurse during the 12 months before the survey.³ Children often present first to their primary care provider, and they may be the first individual who the child shares their suicidal or self-harm thoughts with. It may be useful to have a standardized approach, while using your own clinical judgment, to determine best next steps. Given the significant recent surge in children presenting to the emergency department for psychiatric needs and that environment having its own limitations (for example, long wait times, nontherapeutic space, etc.), a simple screen and brief assessment may lead to being able to maintain a patient safely outside of the hospital.
 

Screen all appropriate patients for suicide

There are, at minimum, three validated screening tools that can be used as to determine what the best next step should be. They include the Ask Suicide-Screening Questions (ASQ) developed by the National Institute of Mental Health, the Columbia-Suicide Severity Rating Scale (C-SSRS), and the PHQ-9 (modified for adolescents). We can highlight one of the screening tools here as noted below, but the choice of screener may be based on facility and/or clinician preference.

The Ask Suicide-Screening Questions

The ASQ, developed by the National Institute of Mental Health, include the following four binary questions plus a fifth acuity question, as follows:

1. In the past few weeks, have you wished you were dead?

2. In the past few weeks, have you felt that you or your family would be better off if you were dead?

3. In the past week, have you been having thoughts about killing yourself?

4. Have you ever tried to kill yourself?

a. If yes, how?

b. When?

The following acuity question is to be asked if any of the above are answered “yes”:

5. Are you having thoughts of killing yourself right now?

a. If yes, please describe.
 

Assess the level of risk

Once you have screened a patient, you need to assess the level of risk to help determine the level of care required. Returning to our original case vignette, does the patient warrant outpatient management, crisis evaluation, or an emergency psychiatric evaluation? You may have already decided that the patient needs an emergency mental health evaluation from a local crisis clinician evaluation and/or the emergency department. However, you may also find that the screen did not elicit imminent concern, but it does warrant a brief assessment to further elucidate the level of risk and proper disposition. One such instrument that may be helpful is the Brief Suicide Safety Assessment (BSSA) – also developed by the NIMH as a tool linked to the ASQ. There are clear and specific instructions in the BSSA with suggestions on how to ask questions. Important components to the BSSA include:

• A focus on a more thorough clinical history – including frequency of suicidal ideation, suicide plan, past behavior, associated symptoms, and social support/stressors
• Collateral information (e.g., further details from those who know the patient such as family/friends).
• Safety planning.
• Determining disposition.

The BSSA may suggest that a crisis/psychiatric evaluation is warranted or suggest that a safety plan with a mental health referral will likely be sufficient.
 

Triage and safety planning

A safety plan should be created if you determine that a patient can be safely maintained as an outpatient based on your screening, assessment, and triaging. Traditional safety plans come in many different forms and can be found online (Example of a Safety Plan Template). However, most safety plans include some version of the following:

• Increased supervision: 24/7 supervision with doors open/unlocked.
• Reduced access: medications (prescription and OTC) locked away; sharps and firearms secured.
• Adaptive coping strategies (e.g., relaxation techniques such as drawing or listening to music).
• Reliable persons for support (e.g., parent, therapist, school counselor).
• Outpatient mental health provider follow-up and/or referral.
• Provision of local crisis and national hotline contact information.
• Use of a safety plan phone app completed with patient.

Envision a safety plan as a living document that evolves, grows, and changes with your patient/family – one that can be easily reviewed/updated at each visit.
 

Returning to our case vignette

Laura returns to your office for a follow-up after a 10-day stay at a hospital-diversion program or inpatient psychiatric unit. The decision is made to use the primary care NIMH ASQ/BSSA algorithm, and you determine the patient to not be at imminent risk following the screen and assessment. Laura is triaged as appropriate for outpatient care, you collaborate to update the safety plan, regular follow-ups are scheduled, and a mental health referral has been placed. Thus, there are tools to assist with screening, assessing, and triaging pediatric patients with suicidal ideation that provide the patient with appropriate care and treatment and may help alleviate the need to have a patient present to the emergency department.

Dr. Abdul-Karim is a child psychiatrist at the University of Vermont University Children’s Hospital in Burlington.

Additional resources

The American Academy of Child and Adolescent Psychiatry has developed information that can be provided to families about suicide safety precautions that can be taken at home, which can be found here: Facts for Families. Suicide Safety: Precautions at Home.

Screening tools listed above can be found here:

ASQ Toolkit.

C-SSRS.

PHQ-9 Modified for Adolescents (PHQ-A).

References

1. Curtin SC. National Center for Health Statistics. “State Suicide Rates Among Adolescents and Young Adults Aged 10-24: United States, 2000-2018” National Vital Statistics Reports..

2. Centers for Disease Control and Prevention, National Center for Health Statistics. “Underlying Cause of Death 2018-2019” CDC WONDER Online Database. Accessed 2021 Jul 31, 6:57:39 p.m.

3. Centers for Disease Control and Prevention. 1991-2019 High School Youth Risk Behavior Survey Data.

Case vignette: Laura is a 14-year-old biological girl who presents to your office for a routine well-child visit. She is doing well medically but notes that over the past 3 months she has been having increasing thoughts of suicide and has self-harmed via cutting on her wrists with a blade removed from a shaving razor. You contemplate what the most salient questions are in order to determine the best disposition for your patient.

The case vignette above may sound like one that you have heard before, and if not, you undoubtedly will encounter such a situation moving forward. The rate of suicidal ideation amongst youth ages 10-24 has increased by 57.4% between 2007 and 2018.¹ Furthermore, suicide is the second leading cause of death in those aged 10 through young adulthood.² According to the Centers for Disease Control and Prevention’s 2019 High School Youth Risk Behavior Survey, 18.8% of high school students seriously considered attempting suicide, 15.7% made a plan about how they would attempt suicide, and 8.9% actually attempted suicide, with 2.5% having a suicide attempt that resulted in an injury, poisoning, or overdose that had to be treated by a doctor or nurse during the 12 months before the survey.³ Children often present first to their primary care provider, and they may be the first individual who the child shares their suicidal or self-harm thoughts with. It may be useful to have a standardized approach, while using your own clinical judgment, to determine best next steps. Given the significant recent surge in children presenting to the emergency department for psychiatric needs and that environment having its own limitations (for example, long wait times, nontherapeutic space, etc.), a simple screen and brief assessment may lead to being able to maintain a patient safely outside of the hospital.
 

Screen all appropriate patients for suicide

There are, at minimum, three validated screening tools that can be used as to determine what the best next step should be. They include the Ask Suicide-Screening Questions (ASQ) developed by the National Institute of Mental Health, the Columbia-Suicide Severity Rating Scale (C-SSRS), and the PHQ-9 (modified for adolescents). We can highlight one of the screening tools here as noted below, but the choice of screener may be based on facility and/or clinician preference.

The Ask Suicide-Screening Questions

The ASQ, developed by the National Institute of Mental Health, include the following four binary questions plus a fifth acuity question, as follows:

1. In the past few weeks, have you wished you were dead?

2. In the past few weeks, have you felt that you or your family would be better off if you were dead?

3. In the past week, have you been having thoughts about killing yourself?

4. Have you ever tried to kill yourself?

a. If yes, how?

b. When?

The following acuity question is to be asked if any of the above are answered “yes”:

5. Are you having thoughts of killing yourself right now?

a. If yes, please describe.
 

Assess the level of risk

Once you have screened a patient, you need to assess the level of risk to help determine the level of care required. Returning to our original case vignette, does the patient warrant outpatient management, crisis evaluation, or an emergency psychiatric evaluation? You may have already decided that the patient needs an emergency mental health evaluation from a local crisis clinician evaluation and/or the emergency department. However, you may also find that the screen did not elicit imminent concern, but it does warrant a brief assessment to further elucidate the level of risk and proper disposition. One such instrument that may be helpful is the Brief Suicide Safety Assessment (BSSA) – also developed by the NIMH as a tool linked to the ASQ. There are clear and specific instructions in the BSSA with suggestions on how to ask questions. Important components to the BSSA include:

• A focus on a more thorough clinical history – including frequency of suicidal ideation, suicide plan, past behavior, associated symptoms, and social support/stressors
• Collateral information (e.g., further details from those who know the patient such as family/friends).
• Safety planning.
• Determining disposition.

The BSSA may suggest that a crisis/psychiatric evaluation is warranted or suggest that a safety plan with a mental health referral will likely be sufficient.
 

Triage and safety planning

A safety plan should be created if you determine that a patient can be safely maintained as an outpatient based on your screening, assessment, and triaging. Traditional safety plans come in many different forms and can be found online (Example of a Safety Plan Template). However, most safety plans include some version of the following:

• Increased supervision: 24/7 supervision with doors open/unlocked.
• Reduced access: medications (prescription and OTC) locked away; sharps and firearms secured.
• Adaptive coping strategies (e.g., relaxation techniques such as drawing or listening to music).
• Reliable persons for support (e.g., parent, therapist, school counselor).
• Outpatient mental health provider follow-up and/or referral.
• Provision of local crisis and national hotline contact information.
• Use of a safety plan phone app completed with patient.

Envision a safety plan as a living document that evolves, grows, and changes with your patient/family – one that can be easily reviewed/updated at each visit.
 

Returning to our case vignette

Laura returns to your office for a follow-up after a 10-day stay at a hospital-diversion program or inpatient psychiatric unit. The decision is made to use the primary care NIMH ASQ/BSSA algorithm, and you determine the patient to not be at imminent risk following the screen and assessment. Laura is triaged as appropriate for outpatient care, you collaborate to update the safety plan, regular follow-ups are scheduled, and a mental health referral has been placed. Thus, there are tools to assist with screening, assessing, and triaging pediatric patients with suicidal ideation that provide the patient with appropriate care and treatment and may help alleviate the need to have a patient present to the emergency department.

Dr. Abdul-Karim is a child psychiatrist at the University of Vermont University Children’s Hospital in Burlington.

Additional resources

The American Academy of Child and Adolescent Psychiatry has developed information that can be provided to families about suicide safety precautions that can be taken at home, which can be found here: Facts for Families. Suicide Safety: Precautions at Home.

Screening tools listed above can be found here:

ASQ Toolkit.

C-SSRS.

PHQ-9 Modified for Adolescents (PHQ-A).

References

1. Curtin SC. National Center for Health Statistics. “State Suicide Rates Among Adolescents and Young Adults Aged 10-24: United States, 2000-2018” National Vital Statistics Reports..

2. Centers for Disease Control and Prevention, National Center for Health Statistics. “Underlying Cause of Death 2018-2019” CDC WONDER Online Database. Accessed 2021 Jul 31, 6:57:39 p.m.

3. Centers for Disease Control and Prevention. 1991-2019 High School Youth Risk Behavior Survey Data.

Case vignette: Laura is a 14-year-old biological girl who presents to your office for a routine well-child visit. She is doing well medically but notes that over the past 3 months she has been having increasing thoughts of suicide and has self-harmed via cutting on her wrists with a blade removed from a shaving razor. You contemplate what the most salient questions are in order to determine the best disposition for your patient.

The case vignette above may sound like one that you have heard before, and if not, you undoubtedly will encounter such a situation moving forward. The rate of suicidal ideation amongst youth ages 10-24 has increased by 57.4% between 2007 and 2018.¹ Furthermore, suicide is the second leading cause of death in those aged 10 through young adulthood.² According to the Centers for Disease Control and Prevention’s 2019 High School Youth Risk Behavior Survey, 18.8% of high school students seriously considered attempting suicide, 15.7% made a plan about how they would attempt suicide, and 8.9% actually attempted suicide, with 2.5% having a suicide attempt that resulted in an injury, poisoning, or overdose that had to be treated by a doctor or nurse during the 12 months before the survey.³ Children often present first to their primary care provider, and they may be the first individual who the child shares their suicidal or self-harm thoughts with. It may be useful to have a standardized approach, while using your own clinical judgment, to determine best next steps. Given the significant recent surge in children presenting to the emergency department for psychiatric needs and that environment having its own limitations (for example, long wait times, nontherapeutic space, etc.), a simple screen and brief assessment may lead to being able to maintain a patient safely outside of the hospital.
 

Screen all appropriate patients for suicide

There are, at minimum, three validated screening tools that can be used as to determine what the best next step should be. They include the Ask Suicide-Screening Questions (ASQ) developed by the National Institute of Mental Health, the Columbia-Suicide Severity Rating Scale (C-SSRS), and the PHQ-9 (modified for adolescents). We can highlight one of the screening tools here as noted below, but the choice of screener may be based on facility and/or clinician preference.

The Ask Suicide-Screening Questions

The ASQ, developed by the National Institute of Mental Health, include the following four binary questions plus a fifth acuity question, as follows:

1. In the past few weeks, have you wished you were dead?

2. In the past few weeks, have you felt that you or your family would be better off if you were dead?

3. In the past week, have you been having thoughts about killing yourself?

4. Have you ever tried to kill yourself?

a. If yes, how?

b. When?

The following acuity question is to be asked if any of the above are answered “yes”:

5. Are you having thoughts of killing yourself right now?

a. If yes, please describe.
 

Assess the level of risk

Once you have screened a patient, you need to assess the level of risk to help determine the level of care required. Returning to our original case vignette, does the patient warrant outpatient management, crisis evaluation, or an emergency psychiatric evaluation? You may have already decided that the patient needs an emergency mental health evaluation from a local crisis clinician evaluation and/or the emergency department. However, you may also find that the screen did not elicit imminent concern, but it does warrant a brief assessment to further elucidate the level of risk and proper disposition. One such instrument that may be helpful is the Brief Suicide Safety Assessment (BSSA) – also developed by the NIMH as a tool linked to the ASQ. There are clear and specific instructions in the BSSA with suggestions on how to ask questions. Important components to the BSSA include:

• A focus on a more thorough clinical history – including frequency of suicidal ideation, suicide plan, past behavior, associated symptoms, and social support/stressors
• Collateral information (e.g., further details from those who know the patient such as family/friends).
• Safety planning.
• Determining disposition.

The BSSA may suggest that a crisis/psychiatric evaluation is warranted or suggest that a safety plan with a mental health referral will likely be sufficient.
 

Triage and safety planning

A safety plan should be created if you determine that a patient can be safely maintained as an outpatient based on your screening, assessment, and triaging. Traditional safety plans come in many different forms and can be found online (Example of a Safety Plan Template). However, most safety plans include some version of the following:

• Increased supervision: 24/7 supervision with doors open/unlocked.
• Reduced access: medications (prescription and OTC) locked away; sharps and firearms secured.
• Adaptive coping strategies (e.g., relaxation techniques such as drawing or listening to music).
• Reliable persons for support (e.g., parent, therapist, school counselor).
• Outpatient mental health provider follow-up and/or referral.
• Provision of local crisis and national hotline contact information.
• Use of a safety plan phone app completed with patient.

Envision a safety plan as a living document that evolves, grows, and changes with your patient/family – one that can be easily reviewed/updated at each visit.
 

Returning to our case vignette

Laura returns to your office for a follow-up after a 10-day stay at a hospital-diversion program or inpatient psychiatric unit. The decision is made to use the primary care NIMH ASQ/BSSA algorithm, and you determine the patient to not be at imminent risk following the screen and assessment. Laura is triaged as appropriate for outpatient care, you collaborate to update the safety plan, regular follow-ups are scheduled, and a mental health referral has been placed. Thus, there are tools to assist with screening, assessing, and triaging pediatric patients with suicidal ideation that provide the patient with appropriate care and treatment and may help alleviate the need to have a patient present to the emergency department.

Dr. Abdul-Karim is a child psychiatrist at the University of Vermont University Children’s Hospital in Burlington.

Additional resources

The American Academy of Child and Adolescent Psychiatry has developed information that can be provided to families about suicide safety precautions that can be taken at home, which can be found here: Facts for Families. Suicide Safety: Precautions at Home.

Screening tools listed above can be found here:

ASQ Toolkit.

C-SSRS.

PHQ-9 Modified for Adolescents (PHQ-A).

References

1. Curtin SC. National Center for Health Statistics. “State Suicide Rates Among Adolescents and Young Adults Aged 10-24: United States, 2000-2018” National Vital Statistics Reports..

2. Centers for Disease Control and Prevention, National Center for Health Statistics. “Underlying Cause of Death 2018-2019” CDC WONDER Online Database. Accessed 2021 Jul 31, 6:57:39 p.m.

3. Centers for Disease Control and Prevention. 1991-2019 High School Youth Risk Behavior Survey Data.

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are “major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being,” co–lead author Jessica O’Loughlin, PhD student, University of Exeter Medical School, United Kingdom, told this news organization.

“Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression,” Ms. O’Loughlin added.

The study was published online July 16 in Human Molecular Genetics.
 

Large body of evidence

A large body of evidence indicates that higher BMI leads to depression.

Ms. O’Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m²) was associated with higher likelihood of depression (odds ratio, 1.50; 95% confidence interval, 1.15-1.95) and lower well-being (beta, -0.15; 95% CI, -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, “higher adiposity remains causal to depression and lowers wellbeing,” the researchers report.

“We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants),” said Ms. O’Loughlin.

“Although we can’t tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (e.g., social stigma) play a role in the relationship between higher BMI and higher odds of depression,” she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

“Finding ways to support people to lose weight could benefit their mental health as well as their physical health,” co–lead author Francesco Casanova, PhD, with the University of Exeter, said in a statement.
 

Unexpected finding

Reached for comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said that “multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders.”

He said this new study is important for three reasons.

“The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger,” Dr. Ahmad noted.

“The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects,” he said in an interview.

“Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety,” Dr. Ahmad added.

“Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator,” he noted.

“Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities,” Dr. Ahmad said.

“Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding,” Dr. Ahmad said.

The study was funded by the Academy of Medical Sciences. Ms. O’Loughlin, Dr. Casanova, and Dr. Ahmad have disclosed no relevant conflicts of interest.

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

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are “major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being,” co–lead author Jessica O’Loughlin, PhD student, University of Exeter Medical School, United Kingdom, told this news organization.

“Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression,” Ms. O’Loughlin added.

The study was published online July 16 in Human Molecular Genetics.
 

Large body of evidence

A large body of evidence indicates that higher BMI leads to depression.

Ms. O’Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m²) was associated with higher likelihood of depression (odds ratio, 1.50; 95% confidence interval, 1.15-1.95) and lower well-being (beta, -0.15; 95% CI, -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, “higher adiposity remains causal to depression and lowers wellbeing,” the researchers report.

“We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants),” said Ms. O’Loughlin.

“Although we can’t tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (e.g., social stigma) play a role in the relationship between higher BMI and higher odds of depression,” she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

“Finding ways to support people to lose weight could benefit their mental health as well as their physical health,” co–lead author Francesco Casanova, PhD, with the University of Exeter, said in a statement.
 

Unexpected finding

Reached for comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said that “multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders.”

He said this new study is important for three reasons.

“The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger,” Dr. Ahmad noted.

“The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects,” he said in an interview.

“Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety,” Dr. Ahmad added.

“Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator,” he noted.

“Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities,” Dr. Ahmad said.

“Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding,” Dr. Ahmad said.

The study was funded by the Academy of Medical Sciences. Ms. O’Loughlin, Dr. Casanova, and Dr. Ahmad have disclosed no relevant conflicts of interest.

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

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are “major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being,” co–lead author Jessica O’Loughlin, PhD student, University of Exeter Medical School, United Kingdom, told this news organization.

“Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression,” Ms. O’Loughlin added.

The study was published online July 16 in Human Molecular Genetics.
 

Large body of evidence

A large body of evidence indicates that higher BMI leads to depression.

Ms. O’Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m²) was associated with higher likelihood of depression (odds ratio, 1.50; 95% confidence interval, 1.15-1.95) and lower well-being (beta, -0.15; 95% CI, -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, “higher adiposity remains causal to depression and lowers wellbeing,” the researchers report.

“We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants),” said Ms. O’Loughlin.

“Although we can’t tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (e.g., social stigma) play a role in the relationship between higher BMI and higher odds of depression,” she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

“Finding ways to support people to lose weight could benefit their mental health as well as their physical health,” co–lead author Francesco Casanova, PhD, with the University of Exeter, said in a statement.
 

Unexpected finding

Reached for comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said that “multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders.”

He said this new study is important for three reasons.

“The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger,” Dr. Ahmad noted.

“The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects,” he said in an interview.

“Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety,” Dr. Ahmad added.

“Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator,” he noted.

“Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities,” Dr. Ahmad said.

“Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding,” Dr. Ahmad said.

The study was funded by the Academy of Medical Sciences. Ms. O’Loughlin, Dr. Casanova, and Dr. Ahmad have disclosed no relevant conflicts of interest.

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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

Although a novel investigational drug that combines dextromethorphan and bupropion (AXS-05, Axsome Therapeutics) met its primary and key secondary endpoints in a phase 2 trial of patients with treatment-resistant depression (TRD), the U.S. Food and Drug Administration has voiced some concerns.

In the MERIT study, AXS-05 significantly delayed time to depression relapse compared with placebo (primary endpoint) – with no relapses observed for at least 6 months. It also significantly prevented depression relapse (secondary endpoint), the company said in a news release announcing the topline results.

The drug has been granted breakthrough therapy designations by the FDA for the treatment of major depressive disorder (MDD) and agitation associated with Alzheimer’s disease.

In addition, the agency is currently reviewing a new drug application (NDA) for AXS-05 for the treatment of MDD, with a target action date of August 22.

However, Axsome stated that the FDA has identified “deficiencies that preclude labeling discussions at this time.”

The company is “attempting to learn the nature of these deficiencies with the goal of addressing them,” Herriot Tabuteau, MD, chief executive officer of Axsome, said in a statement.

However, Dr. Tabuteau acknowledged that this development “may lead to a delay in the potential approval of AXS-05.”
 

‘Well tolerated’

A total of 44 adults with TRD were enrolled into the MERIT study from the long-term, open-label phase 3 trial of AXS-05.

All patients were in stable remission after treatment with AXS-05 and were randomly assigned to continued treatment with AXS-05 (45 mg dextromethorphan/105 mg bupropion twice daily) or to switch to placebo.

Compared with placebo, AXS-05 significantly delayed time to depression relapse (P = .002) and prevented depression relapse (P = .004).

The novel drug was also well tolerated, with no treatment-emergent adverse events reported in more than one participant in the AXS-05 group, the company said.

One patient treated with AXS-05 did experience gout and bacteremia, but these incidents were deemed unrelated to the medication.

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

Although a novel investigational drug that combines dextromethorphan and bupropion (AXS-05, Axsome Therapeutics) met its primary and key secondary endpoints in a phase 2 trial of patients with treatment-resistant depression (TRD), the U.S. Food and Drug Administration has voiced some concerns.

In the MERIT study, AXS-05 significantly delayed time to depression relapse compared with placebo (primary endpoint) – with no relapses observed for at least 6 months. It also significantly prevented depression relapse (secondary endpoint), the company said in a news release announcing the topline results.

The drug has been granted breakthrough therapy designations by the FDA for the treatment of major depressive disorder (MDD) and agitation associated with Alzheimer’s disease.

In addition, the agency is currently reviewing a new drug application (NDA) for AXS-05 for the treatment of MDD, with a target action date of August 22.

However, Axsome stated that the FDA has identified “deficiencies that preclude labeling discussions at this time.”

The company is “attempting to learn the nature of these deficiencies with the goal of addressing them,” Herriot Tabuteau, MD, chief executive officer of Axsome, said in a statement.

However, Dr. Tabuteau acknowledged that this development “may lead to a delay in the potential approval of AXS-05.”
 

‘Well tolerated’

A total of 44 adults with TRD were enrolled into the MERIT study from the long-term, open-label phase 3 trial of AXS-05.

All patients were in stable remission after treatment with AXS-05 and were randomly assigned to continued treatment with AXS-05 (45 mg dextromethorphan/105 mg bupropion twice daily) or to switch to placebo.

Compared with placebo, AXS-05 significantly delayed time to depression relapse (P = .002) and prevented depression relapse (P = .004).

The novel drug was also well tolerated, with no treatment-emergent adverse events reported in more than one participant in the AXS-05 group, the company said.

One patient treated with AXS-05 did experience gout and bacteremia, but these incidents were deemed unrelated to the medication.

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

Although a novel investigational drug that combines dextromethorphan and bupropion (AXS-05, Axsome Therapeutics) met its primary and key secondary endpoints in a phase 2 trial of patients with treatment-resistant depression (TRD), the U.S. Food and Drug Administration has voiced some concerns.

In the MERIT study, AXS-05 significantly delayed time to depression relapse compared with placebo (primary endpoint) – with no relapses observed for at least 6 months. It also significantly prevented depression relapse (secondary endpoint), the company said in a news release announcing the topline results.

The drug has been granted breakthrough therapy designations by the FDA for the treatment of major depressive disorder (MDD) and agitation associated with Alzheimer’s disease.

In addition, the agency is currently reviewing a new drug application (NDA) for AXS-05 for the treatment of MDD, with a target action date of August 22.

However, Axsome stated that the FDA has identified “deficiencies that preclude labeling discussions at this time.”

The company is “attempting to learn the nature of these deficiencies with the goal of addressing them,” Herriot Tabuteau, MD, chief executive officer of Axsome, said in a statement.

However, Dr. Tabuteau acknowledged that this development “may lead to a delay in the potential approval of AXS-05.”
 

‘Well tolerated’

A total of 44 adults with TRD were enrolled into the MERIT study from the long-term, open-label phase 3 trial of AXS-05.

All patients were in stable remission after treatment with AXS-05 and were randomly assigned to continued treatment with AXS-05 (45 mg dextromethorphan/105 mg bupropion twice daily) or to switch to placebo.

Compared with placebo, AXS-05 significantly delayed time to depression relapse (P = .002) and prevented depression relapse (P = .004).

The novel drug was also well tolerated, with no treatment-emergent adverse events reported in more than one participant in the AXS-05 group, the company said.

One patient treated with AXS-05 did experience gout and bacteremia, but these incidents were deemed unrelated to the medication.

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

The COVID-19 pandemic has fueled a growing demand for nurse practitioners (NPs), while demand for primary care physicians has cooled, according to Merritt Hawkins’ annual review of physician and advanced practitioner recruiting trends.

This marks the first time in the review’s 28-year history that NPs have topped the list of the most recruited practitioners, according to the medical search firm. In the 27 prior years, physicians held the top spot. For the previous 14 years, the No. 1 position was held by family physicians.

“COVID-19 and other market forces are changing the dynamics of physician and advanced practitioner recruiting. NPs are coming into their own in a market that puts a premium on easy access to care and cost containment,” Tom Florence, president of Merritt Hawkins, said in a statement.
 

Primary care ‘recruiting frenzy’ over

Mr. Florence said primary care physicians remain a “vital part of team-based care and will be increasingly responsible for coordinating the care of older patients with multiple chronic conditions. But the recruiting frenzy in primary care is over.”

Merritt Hawkins says that overall COVID-19 has had a “severely inhibiting” effect on demand for physicians. The number of searches the company conducted dropped 25%, compared with 2020, and many hospitals and medical groups shut down or lost money during the pandemic.

But the drop-off in demand for physicians is likely to be temporary because the underlying dynamics driving physician supply and demand remain in place, according to the report. These include a growing and aging population, a limited supply of newly trained physicians, and an aging physician workforce.

COVID-19 will not permanently change these market conditions, and demand for physicians already is rebounding, the company said.

The 2021 review of physician and advanced practitioner recruiting is based on a representative sample of 2,458 permanent search engagements that Merritt Hawkins/AMN Healthcare’s physician staffing companies conducted or were in the process of conducting during the 12-month period from April 1, 2020, to March 31, 2021.

Among the key findings:

• 18% of Merritt Hawkins’ recruiting searches were for advanced practitioners, including NPs, physician assistants (PAs), and certified registered nurse anesthetists, up from 13% in the 2020 review. This represents the highest percentage in the 28 years the review has been conducted.
• About two-thirds (64%) of Merritt Hawkins’ search engagements were for physician specialists, including radiologists, psychiatrists, gastroenterologists, and others, “highlighting the robust demand for specialty physicians.”
• In 2021, 18% of Merritt Hawkins’ search engagements were for primary care physicians, down from 20% in 2020 and 22% in 2019, “signaling a relative decline in demand for primary care doctors.”
• Psychiatrists placed fourth on the list of most requested search engagements, a sign of continued strong demand for mental health professionals that is likely to accelerate because of COVID-19.

Starting salaries take a pandemic hit

Owing to the reduced demand for practitioners, starting salaries decreased for many types of health care professions, with the exception of NPs and PAs.

Average starting salaries for NPs showed strong growth, increasing 12% year over year, from $125,000 to $140,000. The average starting salaries for PAs also showed strong growth, increasing by 14% year over year, from $112,000 to $128,000.

Among physicians, interventional cardiologists were offered the highest average starting salaries, at $611,000, followed by orthopedic surgeons, at $546,000. Pediatricians were offered the lowest average starting salaries, at $236,000.

Merritt Hawkins said only 3% of their search engagements were for solo practice or partnership settings, “underscoring the decline of physician private practice.”

Roughly two-thirds (67%) of Merritt Hawkins’ search engagements were in communities of 100,000 people or more, indicating that demand for physicians and advanced practitioners is not limited to small or rural communities.

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

The COVID-19 pandemic has fueled a growing demand for nurse practitioners (NPs), while demand for primary care physicians has cooled, according to Merritt Hawkins’ annual review of physician and advanced practitioner recruiting trends.

This marks the first time in the review’s 28-year history that NPs have topped the list of the most recruited practitioners, according to the medical search firm. In the 27 prior years, physicians held the top spot. For the previous 14 years, the No. 1 position was held by family physicians.

“COVID-19 and other market forces are changing the dynamics of physician and advanced practitioner recruiting. NPs are coming into their own in a market that puts a premium on easy access to care and cost containment,” Tom Florence, president of Merritt Hawkins, said in a statement.
 

Primary care ‘recruiting frenzy’ over

Mr. Florence said primary care physicians remain a “vital part of team-based care and will be increasingly responsible for coordinating the care of older patients with multiple chronic conditions. But the recruiting frenzy in primary care is over.”

Merritt Hawkins says that overall COVID-19 has had a “severely inhibiting” effect on demand for physicians. The number of searches the company conducted dropped 25%, compared with 2020, and many hospitals and medical groups shut down or lost money during the pandemic.

But the drop-off in demand for physicians is likely to be temporary because the underlying dynamics driving physician supply and demand remain in place, according to the report. These include a growing and aging population, a limited supply of newly trained physicians, and an aging physician workforce.

COVID-19 will not permanently change these market conditions, and demand for physicians already is rebounding, the company said.

The 2021 review of physician and advanced practitioner recruiting is based on a representative sample of 2,458 permanent search engagements that Merritt Hawkins/AMN Healthcare’s physician staffing companies conducted or were in the process of conducting during the 12-month period from April 1, 2020, to March 31, 2021.

Among the key findings:

• 18% of Merritt Hawkins’ recruiting searches were for advanced practitioners, including NPs, physician assistants (PAs), and certified registered nurse anesthetists, up from 13% in the 2020 review. This represents the highest percentage in the 28 years the review has been conducted.
• About two-thirds (64%) of Merritt Hawkins’ search engagements were for physician specialists, including radiologists, psychiatrists, gastroenterologists, and others, “highlighting the robust demand for specialty physicians.”
• In 2021, 18% of Merritt Hawkins’ search engagements were for primary care physicians, down from 20% in 2020 and 22% in 2019, “signaling a relative decline in demand for primary care doctors.”
• Psychiatrists placed fourth on the list of most requested search engagements, a sign of continued strong demand for mental health professionals that is likely to accelerate because of COVID-19.

Starting salaries take a pandemic hit

Owing to the reduced demand for practitioners, starting salaries decreased for many types of health care professions, with the exception of NPs and PAs.

Average starting salaries for NPs showed strong growth, increasing 12% year over year, from $125,000 to $140,000. The average starting salaries for PAs also showed strong growth, increasing by 14% year over year, from $112,000 to $128,000.

Among physicians, interventional cardiologists were offered the highest average starting salaries, at $611,000, followed by orthopedic surgeons, at $546,000. Pediatricians were offered the lowest average starting salaries, at $236,000.

Merritt Hawkins said only 3% of their search engagements were for solo practice or partnership settings, “underscoring the decline of physician private practice.”

Roughly two-thirds (67%) of Merritt Hawkins’ search engagements were in communities of 100,000 people or more, indicating that demand for physicians and advanced practitioners is not limited to small or rural communities.

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

The COVID-19 pandemic has fueled a growing demand for nurse practitioners (NPs), while demand for primary care physicians has cooled, according to Merritt Hawkins’ annual review of physician and advanced practitioner recruiting trends.

This marks the first time in the review’s 28-year history that NPs have topped the list of the most recruited practitioners, according to the medical search firm. In the 27 prior years, physicians held the top spot. For the previous 14 years, the No. 1 position was held by family physicians.

“COVID-19 and other market forces are changing the dynamics of physician and advanced practitioner recruiting. NPs are coming into their own in a market that puts a premium on easy access to care and cost containment,” Tom Florence, president of Merritt Hawkins, said in a statement.
 

Primary care ‘recruiting frenzy’ over

Mr. Florence said primary care physicians remain a “vital part of team-based care and will be increasingly responsible for coordinating the care of older patients with multiple chronic conditions. But the recruiting frenzy in primary care is over.”

Merritt Hawkins says that overall COVID-19 has had a “severely inhibiting” effect on demand for physicians. The number of searches the company conducted dropped 25%, compared with 2020, and many hospitals and medical groups shut down or lost money during the pandemic.

But the drop-off in demand for physicians is likely to be temporary because the underlying dynamics driving physician supply and demand remain in place, according to the report. These include a growing and aging population, a limited supply of newly trained physicians, and an aging physician workforce.

COVID-19 will not permanently change these market conditions, and demand for physicians already is rebounding, the company said.

The 2021 review of physician and advanced practitioner recruiting is based on a representative sample of 2,458 permanent search engagements that Merritt Hawkins/AMN Healthcare’s physician staffing companies conducted or were in the process of conducting during the 12-month period from April 1, 2020, to March 31, 2021.

Among the key findings:

• 18% of Merritt Hawkins’ recruiting searches were for advanced practitioners, including NPs, physician assistants (PAs), and certified registered nurse anesthetists, up from 13% in the 2020 review. This represents the highest percentage in the 28 years the review has been conducted.
• About two-thirds (64%) of Merritt Hawkins’ search engagements were for physician specialists, including radiologists, psychiatrists, gastroenterologists, and others, “highlighting the robust demand for specialty physicians.”
• In 2021, 18% of Merritt Hawkins’ search engagements were for primary care physicians, down from 20% in 2020 and 22% in 2019, “signaling a relative decline in demand for primary care doctors.”
• Psychiatrists placed fourth on the list of most requested search engagements, a sign of continued strong demand for mental health professionals that is likely to accelerate because of COVID-19.

Starting salaries take a pandemic hit

Owing to the reduced demand for practitioners, starting salaries decreased for many types of health care professions, with the exception of NPs and PAs.

Average starting salaries for NPs showed strong growth, increasing 12% year over year, from $125,000 to $140,000. The average starting salaries for PAs also showed strong growth, increasing by 14% year over year, from $112,000 to $128,000.

Among physicians, interventional cardiologists were offered the highest average starting salaries, at $611,000, followed by orthopedic surgeons, at $546,000. Pediatricians were offered the lowest average starting salaries, at $236,000.

Merritt Hawkins said only 3% of their search engagements were for solo practice or partnership settings, “underscoring the decline of physician private practice.”

Roughly two-thirds (67%) of Merritt Hawkins’ search engagements were in communities of 100,000 people or more, indicating that demand for physicians and advanced practitioners is not limited to small or rural communities.

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

The current pandemic is forcing changes throughout the health care industry. Telehealth is witnessing a surge. Hospitals are struggling without elective care, and remarkably, physicians are being laid off during a time of crisis. While some states have a surplus work force, other states go begging, and they lock the system up with delays in the processing of applications.

Considering the prevalence of noncompete clauses and a schism in state-to-state processing of complaints, patients are suffering and dying under an antiquated system. The Federation of State Medical Boards doesn’t seem to add to the solution, but instead confounds the problem with new directives. The time is nigh for the federal government to eliminate state medical licensure and replace it with a national medical license for all physicians and health care professionals.

Because physicians’ training requirements don’t vary from state to state, it makes sense. We must take national standardized exams to qualify. Locum tenens physicians must maintain licensure in as many states as they practice; this creates an unnecessary burden and expense, when there is a better alternative. Some states have arranged reciprocity licensure with other states. This is commendable but doesn’t go far enough to manage national shortages in rural areas.

Under a national licensing system, physicians and other health care professionals would not only be free to travel anywhere in the United States to practice, they can count on consistent and equal management of their license. The federal government can track regional overages and shortages and redirect physicians and other medical professionals with incentives to areas in need.

The FSMB claims that there is interstate continuity among state medical boards, but the data don’t support this.

Why is this the case? Each medical board fails to manage their charges equally. Often, action taken by one state board when reported to another state board can cause a review and readjudication. This occasionally results in the overturning of a reprimand or suspension because of differences in legislation.

Yet the physician or health care professional must bear the burden of the notification against their license. Once again, the FSMB claims there is interstate continuity in disciplinary actions, but the data do not support this.

Once someone brings a complaint against a health professional, which in this health care climate is inevitable, the medical board must institute an investigation. Even if it has no merit, the process must go forward. Under a national system, a consistent approach to dismiss and investigate issues and complaints might expedite the process. This eliminates inefficiency and delays in clearance of charges.

A report in 2006 identified fragmentation and discontinuities in the way each state medical board manages a physician or other health care personnel’s complaints. The number of hands involved in the process varies and is often onerous and redundant. Several sources may request the same information, tying it up as it moves through an inefficient and uncooperative system. With the increase in internal politics since then, this only compounds rather than improves the problem.

Yet the benefit of national licensure is not just for the health care personnel but also for insurance companies that must register and screen physicians as they move from region to region. In each state, the physician must repeat the accreditation process, delaying reimbursements and denying care. Hospitals also must repeat the credentialing task as well. This, although the physician or health care worker has a clean record with the same company or the same hospital system in their original state.

Perhaps data from one insurance group or hospital in another state get lost or altered in transfer, but under national licensing, this would not be possible. Furthermore, the current system limits the individual professional’s input. By nationalizing, record corrections would go through a federal database rather than state data banks that don’t sync.

This already partially exists with the National Practitioner Identifier. But we can take it one step further. Through nationalization, we could institute a fairer system of reporting where both the professional’s and the complainant’s summary is included. One might argue the National Physician Data Bank performs this function, but in fact, it merely reflects state assessments – which again vary.

The infrastructure is already in place to transition from a state to national system with facilities and records kept in each state’s medical board. It would simply be a matter of replacing state personnel with federal employees who all work from the same script. A national medical license simply makes sense for all parties. It reduces discontinuity and increases efficiency. A national medical license empowers the individual rather than institutions, yet benefits both.

The time is nigh to nationally certify and set physicians free, reduce paperwork and needless fees, and eliminate state supremacy.  


Dr. Raymond is an emergency physician based in Hickory, N.C., and Muckendorf an der Donau, Austria.

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

The current pandemic is forcing changes throughout the health care industry. Telehealth is witnessing a surge. Hospitals are struggling without elective care, and remarkably, physicians are being laid off during a time of crisis. While some states have a surplus work force, other states go begging, and they lock the system up with delays in the processing of applications.

Considering the prevalence of noncompete clauses and a schism in state-to-state processing of complaints, patients are suffering and dying under an antiquated system. The Federation of State Medical Boards doesn’t seem to add to the solution, but instead confounds the problem with new directives. The time is nigh for the federal government to eliminate state medical licensure and replace it with a national medical license for all physicians and health care professionals.

Because physicians’ training requirements don’t vary from state to state, it makes sense. We must take national standardized exams to qualify. Locum tenens physicians must maintain licensure in as many states as they practice; this creates an unnecessary burden and expense, when there is a better alternative. Some states have arranged reciprocity licensure with other states. This is commendable but doesn’t go far enough to manage national shortages in rural areas.

Under a national licensing system, physicians and other health care professionals would not only be free to travel anywhere in the United States to practice, they can count on consistent and equal management of their license. The federal government can track regional overages and shortages and redirect physicians and other medical professionals with incentives to areas in need.

The FSMB claims that there is interstate continuity among state medical boards, but the data don’t support this.

Why is this the case? Each medical board fails to manage their charges equally. Often, action taken by one state board when reported to another state board can cause a review and readjudication. This occasionally results in the overturning of a reprimand or suspension because of differences in legislation.

Yet the physician or health care professional must bear the burden of the notification against their license. Once again, the FSMB claims there is interstate continuity in disciplinary actions, but the data do not support this.

Once someone brings a complaint against a health professional, which in this health care climate is inevitable, the medical board must institute an investigation. Even if it has no merit, the process must go forward. Under a national system, a consistent approach to dismiss and investigate issues and complaints might expedite the process. This eliminates inefficiency and delays in clearance of charges.

A report in 2006 identified fragmentation and discontinuities in the way each state medical board manages a physician or other health care personnel’s complaints. The number of hands involved in the process varies and is often onerous and redundant. Several sources may request the same information, tying it up as it moves through an inefficient and uncooperative system. With the increase in internal politics since then, this only compounds rather than improves the problem.

Yet the benefit of national licensure is not just for the health care personnel but also for insurance companies that must register and screen physicians as they move from region to region. In each state, the physician must repeat the accreditation process, delaying reimbursements and denying care. Hospitals also must repeat the credentialing task as well. This, although the physician or health care worker has a clean record with the same company or the same hospital system in their original state.

Perhaps data from one insurance group or hospital in another state get lost or altered in transfer, but under national licensing, this would not be possible. Furthermore, the current system limits the individual professional’s input. By nationalizing, record corrections would go through a federal database rather than state data banks that don’t sync.

This already partially exists with the National Practitioner Identifier. But we can take it one step further. Through nationalization, we could institute a fairer system of reporting where both the professional’s and the complainant’s summary is included. One might argue the National Physician Data Bank performs this function, but in fact, it merely reflects state assessments – which again vary.

The infrastructure is already in place to transition from a state to national system with facilities and records kept in each state’s medical board. It would simply be a matter of replacing state personnel with federal employees who all work from the same script. A national medical license simply makes sense for all parties. It reduces discontinuity and increases efficiency. A national medical license empowers the individual rather than institutions, yet benefits both.

The time is nigh to nationally certify and set physicians free, reduce paperwork and needless fees, and eliminate state supremacy.  


Dr. Raymond is an emergency physician based in Hickory, N.C., and Muckendorf an der Donau, Austria.

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

The current pandemic is forcing changes throughout the health care industry. Telehealth is witnessing a surge. Hospitals are struggling without elective care, and remarkably, physicians are being laid off during a time of crisis. While some states have a surplus work force, other states go begging, and they lock the system up with delays in the processing of applications.

Considering the prevalence of noncompete clauses and a schism in state-to-state processing of complaints, patients are suffering and dying under an antiquated system. The Federation of State Medical Boards doesn’t seem to add to the solution, but instead confounds the problem with new directives. The time is nigh for the federal government to eliminate state medical licensure and replace it with a national medical license for all physicians and health care professionals.

Because physicians’ training requirements don’t vary from state to state, it makes sense. We must take national standardized exams to qualify. Locum tenens physicians must maintain licensure in as many states as they practice; this creates an unnecessary burden and expense, when there is a better alternative. Some states have arranged reciprocity licensure with other states. This is commendable but doesn’t go far enough to manage national shortages in rural areas.

Under a national licensing system, physicians and other health care professionals would not only be free to travel anywhere in the United States to practice, they can count on consistent and equal management of their license. The federal government can track regional overages and shortages and redirect physicians and other medical professionals with incentives to areas in need.

The FSMB claims that there is interstate continuity among state medical boards, but the data don’t support this.

Why is this the case? Each medical board fails to manage their charges equally. Often, action taken by one state board when reported to another state board can cause a review and readjudication. This occasionally results in the overturning of a reprimand or suspension because of differences in legislation.

Yet the physician or health care professional must bear the burden of the notification against their license. Once again, the FSMB claims there is interstate continuity in disciplinary actions, but the data do not support this.

Once someone brings a complaint against a health professional, which in this health care climate is inevitable, the medical board must institute an investigation. Even if it has no merit, the process must go forward. Under a national system, a consistent approach to dismiss and investigate issues and complaints might expedite the process. This eliminates inefficiency and delays in clearance of charges.

A report in 2006 identified fragmentation and discontinuities in the way each state medical board manages a physician or other health care personnel’s complaints. The number of hands involved in the process varies and is often onerous and redundant. Several sources may request the same information, tying it up as it moves through an inefficient and uncooperative system. With the increase in internal politics since then, this only compounds rather than improves the problem.

Yet the benefit of national licensure is not just for the health care personnel but also for insurance companies that must register and screen physicians as they move from region to region. In each state, the physician must repeat the accreditation process, delaying reimbursements and denying care. Hospitals also must repeat the credentialing task as well. This, although the physician or health care worker has a clean record with the same company or the same hospital system in their original state.

Perhaps data from one insurance group or hospital in another state get lost or altered in transfer, but under national licensing, this would not be possible. Furthermore, the current system limits the individual professional’s input. By nationalizing, record corrections would go through a federal database rather than state data banks that don’t sync.

This already partially exists with the National Practitioner Identifier. But we can take it one step further. Through nationalization, we could institute a fairer system of reporting where both the professional’s and the complainant’s summary is included. One might argue the National Physician Data Bank performs this function, but in fact, it merely reflects state assessments – which again vary.

The infrastructure is already in place to transition from a state to national system with facilities and records kept in each state’s medical board. It would simply be a matter of replacing state personnel with federal employees who all work from the same script. A national medical license simply makes sense for all parties. It reduces discontinuity and increases efficiency. A national medical license empowers the individual rather than institutions, yet benefits both.

The time is nigh to nationally certify and set physicians free, reduce paperwork and needless fees, and eliminate state supremacy.  


Dr. Raymond is an emergency physician based in Hickory, N.C., and Muckendorf an der Donau, Austria.

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