Federal Practitioner

A federal advisory panel recommends that health care workers and residents of long-term care facilities be the first to receive a COVID-19 vaccine when one is authorized for use by the Food and Drug Administration.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.

The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.

“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.

Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.

“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.

“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”

CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.

But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.

She added: “I have no reservations for health care workers taking this vaccine.”
 

Prioritization could change

The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.

“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.

He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.

A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.

“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.

ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
 

Staggered immunization subprioritization urged

The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.

“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.

The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.

Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.

Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.

The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.

ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.

This article first appeared on Medscape.com.

A federal advisory panel recommends that health care workers and residents of long-term care facilities be the first to receive a COVID-19 vaccine when one is authorized for use by the Food and Drug Administration.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.

The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.

“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.

Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.

“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.

“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”

CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.

But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.

She added: “I have no reservations for health care workers taking this vaccine.”
 

Prioritization could change

The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.

“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.

He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.

A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.

“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.

ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
 

Staggered immunization subprioritization urged

The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.

“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.

The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.

Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.

Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.

The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.

ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.

This article first appeared on Medscape.com.

A federal advisory panel recommends that health care workers and residents of long-term care facilities be the first to receive a COVID-19 vaccine when one is authorized for use by the Food and Drug Administration.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.

The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.

“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.

Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.

“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.

“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”

CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.

But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.

She added: “I have no reservations for health care workers taking this vaccine.”
 

Prioritization could change

The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.

“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.

He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.

A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.

“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.

ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
 

Staggered immunization subprioritization urged

The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.

“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.

The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.

Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.

Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.

The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.

ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.

This article first appeared on Medscape.com.

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

Since the start of the pandemic, we have been conducting an extra hour of Virtual Rounds at the Center for Women’s Mental Health. Virtual Rounds has been an opportunity to discuss cases around a spectrum of clinical management issues with respect to depression, bipolar disorder, and a spectrum of anxiety disorders like obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder. How to apply the calculus of risk-benefit decision-making around management of psychiatric disorder during pregnancy and the postpartum period has been the cornerstone of the work at our center for over 2 decades.

When we went virtual at our center in the early Spring, we decided to keep the format of our faculty rounds the way they have been for years and to sustain cohesiveness of our program during the pandemic. But we thought the needs of pregnant and postpartum women warranted being addressed in a context more specific to COVID-19, and also that reproductive psychiatrists and other clinicians could learn from each other about novel issues coming up for this group of patients during the pandemic. With that backdrop, Marlene Freeman, MD, and I founded “Virtual Rounds at the Center” to respond to queries from our colleagues across the country; we do this just after our own rounds on Wednesdays at 2:00 p.m.

As the pandemic has progressed, Virtual Rounds has blossomed into a virtual community on the Zoom platform, where social workers, psychologists, nurse prescribers, psychiatrists, and obstetricians discuss the needs of pregnant and postpartum women specific to COVID-19. Frequently, our discussions involve a review of the risks and benefits of treatment before, during, and after pregnancy.

Seemingly, week to week, more and more colleagues raise questions about the treatment of anxiety and insomnia during pregnancy and the postpartum period. I’ve spoken in previous columns about the enhanced use of telemedicine. Telemedicine not only facilitates efforts like Virtual Rounds and our ability to reach out to colleagues across the country and share cases, but also has allowed us to keep even closer tabs on the emotional well-being of our pregnant and postpartum women during COVID-19.

The question is not just about the effects of a medicine that a woman might take to treat anxiety or insomnia during pregnancy, but the experience of the pandemic per se, which we are measuring in multiple studies now using a variety of psychological instruments that patients complete. The pandemic is unequivocally taking a still unquantified toll on the mental health of Americans and potentially on the next generation to come.

Midcycle awakening during pregnancy

Complaints of insomnia and midcycle awakening during pregnancy are not new – it is the rule, rather than the exception for many pregnant women, particularly later in pregnancy. We have unequivocally seen a worsening of complaints of sleep disruption including insomnia and midcycle awakening during the pandemic that is greater than what we have seen previously. Both patients and colleagues have asked us the safest ways to manage it. One of the first things we consider when we hear about insomnia is whether it is part of an underlying mood disorder. While we see primary insomnia clinically, it really is important to remember that insomnia can be part and parcel of an underlying mood disorder.

With that in mind, what are the options? During the pandemic, we’ve seen an increased use of digital cognitive behavioral therapy for insomnia (CBT-I) for patients who cannot initiate sleep, which has a very strong evidence base for effectiveness as a first-line intervention for many.

If a patient has an incomplete response to CBT-I, what might be pursued next? In our center, we have a low threshold for using low doses of benzodiazepines, such as lorazepam or clonazepam, because the majority of data do not support an increased risk of major congenital malformations even when used in the first trimester. It is quite common to see medicines such as newer nonbenzodiazepine sedative hypnotics such as Ambien CR (zolpidem) or Lunesta (eszopiclone) used by our colleagues in ob.gyn. The reproductive safety data on those medicines are particularly sparse, and they may have greater risk of cognitive side effects the next day, so we tend to avoid them.

Another sometimes-forgotten option to consider is using low doses of tricyclic antidepressants (i.e., 10-25 mg of nortriptyline at bedtime), with tricyclics having a 40-year history and at least one pooled analysis showing the absence of increased risk for major congenital malformations when used. This may be a very easy way of managing insomnia, with low-dose tricyclics having an anxiolytic effect as well.

Anxiety during pregnancy

The most common rise in symptoms during COVID-19 for women who are pregnant or post partum has been an increase in anxiety. Women present with a spectrum of concerns leading to anxiety symptoms in the context of the pandemic. Earlier on in the pandemic, concerns focused mostly on how to stay healthy, and how to mitigate risk and not catch SARS-CoV-2 during pregnancy, as well as the very complex issues that were playing out in real time as hospital systems were figuring out how to manage pregnant women in labor and to keep both them and staff safe. Over time, anxiety has shifted to still staying safe during the pandemic and the potential impact of SARS-CoV-2 infection on pregnancy outcomes. The No. 1 concern is what the implications of COVID-19 disease are on mother and child. New mothers also are anxious about how they will practically navigate life with a newborn in the postpartum setting.

Early on in the pandemic, some hospital systems severely limited who was in the room with a woman during labor, potentially impeding the wishes of women during delivery who would have wanted their loved ones and/or a doula present, as an example. With enhanced testing available now, protocols have since relaxed in many hospitals to allow partners – but not a team – to remain in the hospital during the labor process. Still, the prospect of delivering during a pandemic is undoubtedly a source of anxiety for some women.

This sort of anxiety, particularly in patients with preexisting anxiety disorders, can be particularly challenging. Fortunately, there has been a rapid increase over the last several years of digital apps to mitigate anxiety. While many of them have not been systematically studied, the data on biobehavioral intervention for anxiety is enormous, and this should be used as first-line treatment for patients with mild to moderate symptoms; so many women would prefer to avoid pharmacological intervention during pregnancy, if possible, to avoid fetal drug exposure. For patients who meet criteria for frank anxiety disorder, other nonpharmacologic interventions such as CBT have been shown to be effective.

Frequently, we see women who are experiencing levels of anxiety where nonpharmacological interventions have an incomplete response, and colleagues have asked about the safest way to treat these patients. As has been discussed in multiple previous columns, selective serotonin reuptake inhibitors (SSRIs) should be thought of sooner rather than later, particularly with medicines with good reproductive safety data such as sertraline, citalopram, or fluoxetine.

We also reported over 15 years ago that at least 30%-40% of women presenting with histories of recurrent major depression at the beginning of pregnancy had comorbid anxiety disorders, and that the use of benzodiazepines in that population in addition to SSRIs was exceedingly common, with doses of approximately 0.5-1.5 mg of clonazepam or lorazepam being standard fare. Again, this is very appropriate treatment to mitigate anxiety symptoms because now have enough data as a field that support the existence of adverse outcomes associated with untreated anxiety during pregnancy in terms of both adverse obstetric and neonatal outcomes, higher rates of preterm birth, and other obstetric complications. Hence, managing anxiety during pregnancy should be considered like managing a toxic exposure – the same way that one would be concerned about anything else that a pregnant woman could be exposed to.

Lastly, although no atypical antipsychotic has been approved for the treatment of anxiety, its use off label is extremely common. More and more data support the absence of a signal of teratogenicity across the family of molecules including atypical antipsychotics. Beyond potential use of atypical antipsychotics, at Virtual Rounds last week, a colleague asked about the use of gabapentin in a patient who was diagnosed with substance use disorder and who had inadvertently conceived on gabapentin, which was being used to treat both anxiety and insomnia. We have typically avoided the use of gabapentin during pregnancy because prospective data have been limited to relatively small case series and one report, with a total of exposures in roughly the 300 range.

However, our colleagues at the Harvard School of Public Health have recently published an article that looked at the United States Medicaid Analytic eXtract (MAX) dataset, which has been used to publish other articles addressing atypical antipsychotics, SSRIs, lithium, and pharmacovigilance investigations among other important topics. In this study, the database was used to look specifically at 4,642 pregnancies with gabapentin exposure relative to 1,744,447 unexposed pregnancies, without a significant finding for increased risk for major congenital malformations.

The question of an increased risk of cardiac malformations and of increased risk for obstetric complications are difficult to untangle from anxiety and depression, as they also are associated with those same outcomes. With that said, the analysis is a welcome addition to our knowledge base for a medicine used more widely to treat symptoms such as anxiety and insomnia in the general population, with a question mark around where it may fit into the algorithm during pregnancy.

In our center, gabapentin still would not be used as a first-line treatment for the management of anxiety or insomnia during pregnancy. But these new data still are reassuring for patients who come in, frequently with unplanned pregnancies. It is an important reminder to those of us taking care of patients during the pandemic to review use of contraception, because although data are unavailable specific to the period of the pandemic, what is clear is that, even prior to COVID-19, 50% of pregnancies in America were unplanned. Addressing issues of reliable use of contraception, particularly during the pandemic, is that much more important.

In this particular case, our clinician colleague in Virtual Rounds decided to continue gabapentin across pregnancy in the context of these reassuring data, but others may choose to discontinue or pursue some of the other treatment options noted above.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Since the start of the pandemic, we have been conducting an extra hour of Virtual Rounds at the Center for Women’s Mental Health. Virtual Rounds has been an opportunity to discuss cases around a spectrum of clinical management issues with respect to depression, bipolar disorder, and a spectrum of anxiety disorders like obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder. How to apply the calculus of risk-benefit decision-making around management of psychiatric disorder during pregnancy and the postpartum period has been the cornerstone of the work at our center for over 2 decades.

When we went virtual at our center in the early Spring, we decided to keep the format of our faculty rounds the way they have been for years and to sustain cohesiveness of our program during the pandemic. But we thought the needs of pregnant and postpartum women warranted being addressed in a context more specific to COVID-19, and also that reproductive psychiatrists and other clinicians could learn from each other about novel issues coming up for this group of patients during the pandemic. With that backdrop, Marlene Freeman, MD, and I founded “Virtual Rounds at the Center” to respond to queries from our colleagues across the country; we do this just after our own rounds on Wednesdays at 2:00 p.m.

As the pandemic has progressed, Virtual Rounds has blossomed into a virtual community on the Zoom platform, where social workers, psychologists, nurse prescribers, psychiatrists, and obstetricians discuss the needs of pregnant and postpartum women specific to COVID-19. Frequently, our discussions involve a review of the risks and benefits of treatment before, during, and after pregnancy.

Seemingly, week to week, more and more colleagues raise questions about the treatment of anxiety and insomnia during pregnancy and the postpartum period. I’ve spoken in previous columns about the enhanced use of telemedicine. Telemedicine not only facilitates efforts like Virtual Rounds and our ability to reach out to colleagues across the country and share cases, but also has allowed us to keep even closer tabs on the emotional well-being of our pregnant and postpartum women during COVID-19.

The question is not just about the effects of a medicine that a woman might take to treat anxiety or insomnia during pregnancy, but the experience of the pandemic per se, which we are measuring in multiple studies now using a variety of psychological instruments that patients complete. The pandemic is unequivocally taking a still unquantified toll on the mental health of Americans and potentially on the next generation to come.

Midcycle awakening during pregnancy

Complaints of insomnia and midcycle awakening during pregnancy are not new – it is the rule, rather than the exception for many pregnant women, particularly later in pregnancy. We have unequivocally seen a worsening of complaints of sleep disruption including insomnia and midcycle awakening during the pandemic that is greater than what we have seen previously. Both patients and colleagues have asked us the safest ways to manage it. One of the first things we consider when we hear about insomnia is whether it is part of an underlying mood disorder. While we see primary insomnia clinically, it really is important to remember that insomnia can be part and parcel of an underlying mood disorder.

With that in mind, what are the options? During the pandemic, we’ve seen an increased use of digital cognitive behavioral therapy for insomnia (CBT-I) for patients who cannot initiate sleep, which has a very strong evidence base for effectiveness as a first-line intervention for many.

If a patient has an incomplete response to CBT-I, what might be pursued next? In our center, we have a low threshold for using low doses of benzodiazepines, such as lorazepam or clonazepam, because the majority of data do not support an increased risk of major congenital malformations even when used in the first trimester. It is quite common to see medicines such as newer nonbenzodiazepine sedative hypnotics such as Ambien CR (zolpidem) or Lunesta (eszopiclone) used by our colleagues in ob.gyn. The reproductive safety data on those medicines are particularly sparse, and they may have greater risk of cognitive side effects the next day, so we tend to avoid them.

Another sometimes-forgotten option to consider is using low doses of tricyclic antidepressants (i.e., 10-25 mg of nortriptyline at bedtime), with tricyclics having a 40-year history and at least one pooled analysis showing the absence of increased risk for major congenital malformations when used. This may be a very easy way of managing insomnia, with low-dose tricyclics having an anxiolytic effect as well.

Anxiety during pregnancy

The most common rise in symptoms during COVID-19 for women who are pregnant or post partum has been an increase in anxiety. Women present with a spectrum of concerns leading to anxiety symptoms in the context of the pandemic. Earlier on in the pandemic, concerns focused mostly on how to stay healthy, and how to mitigate risk and not catch SARS-CoV-2 during pregnancy, as well as the very complex issues that were playing out in real time as hospital systems were figuring out how to manage pregnant women in labor and to keep both them and staff safe. Over time, anxiety has shifted to still staying safe during the pandemic and the potential impact of SARS-CoV-2 infection on pregnancy outcomes. The No. 1 concern is what the implications of COVID-19 disease are on mother and child. New mothers also are anxious about how they will practically navigate life with a newborn in the postpartum setting.

Early on in the pandemic, some hospital systems severely limited who was in the room with a woman during labor, potentially impeding the wishes of women during delivery who would have wanted their loved ones and/or a doula present, as an example. With enhanced testing available now, protocols have since relaxed in many hospitals to allow partners – but not a team – to remain in the hospital during the labor process. Still, the prospect of delivering during a pandemic is undoubtedly a source of anxiety for some women.

This sort of anxiety, particularly in patients with preexisting anxiety disorders, can be particularly challenging. Fortunately, there has been a rapid increase over the last several years of digital apps to mitigate anxiety. While many of them have not been systematically studied, the data on biobehavioral intervention for anxiety is enormous, and this should be used as first-line treatment for patients with mild to moderate symptoms; so many women would prefer to avoid pharmacological intervention during pregnancy, if possible, to avoid fetal drug exposure. For patients who meet criteria for frank anxiety disorder, other nonpharmacologic interventions such as CBT have been shown to be effective.

Frequently, we see women who are experiencing levels of anxiety where nonpharmacological interventions have an incomplete response, and colleagues have asked about the safest way to treat these patients. As has been discussed in multiple previous columns, selective serotonin reuptake inhibitors (SSRIs) should be thought of sooner rather than later, particularly with medicines with good reproductive safety data such as sertraline, citalopram, or fluoxetine.

We also reported over 15 years ago that at least 30%-40% of women presenting with histories of recurrent major depression at the beginning of pregnancy had comorbid anxiety disorders, and that the use of benzodiazepines in that population in addition to SSRIs was exceedingly common, with doses of approximately 0.5-1.5 mg of clonazepam or lorazepam being standard fare. Again, this is very appropriate treatment to mitigate anxiety symptoms because now have enough data as a field that support the existence of adverse outcomes associated with untreated anxiety during pregnancy in terms of both adverse obstetric and neonatal outcomes, higher rates of preterm birth, and other obstetric complications. Hence, managing anxiety during pregnancy should be considered like managing a toxic exposure – the same way that one would be concerned about anything else that a pregnant woman could be exposed to.

Lastly, although no atypical antipsychotic has been approved for the treatment of anxiety, its use off label is extremely common. More and more data support the absence of a signal of teratogenicity across the family of molecules including atypical antipsychotics. Beyond potential use of atypical antipsychotics, at Virtual Rounds last week, a colleague asked about the use of gabapentin in a patient who was diagnosed with substance use disorder and who had inadvertently conceived on gabapentin, which was being used to treat both anxiety and insomnia. We have typically avoided the use of gabapentin during pregnancy because prospective data have been limited to relatively small case series and one report, with a total of exposures in roughly the 300 range.

However, our colleagues at the Harvard School of Public Health have recently published an article that looked at the United States Medicaid Analytic eXtract (MAX) dataset, which has been used to publish other articles addressing atypical antipsychotics, SSRIs, lithium, and pharmacovigilance investigations among other important topics. In this study, the database was used to look specifically at 4,642 pregnancies with gabapentin exposure relative to 1,744,447 unexposed pregnancies, without a significant finding for increased risk for major congenital malformations.

The question of an increased risk of cardiac malformations and of increased risk for obstetric complications are difficult to untangle from anxiety and depression, as they also are associated with those same outcomes. With that said, the analysis is a welcome addition to our knowledge base for a medicine used more widely to treat symptoms such as anxiety and insomnia in the general population, with a question mark around where it may fit into the algorithm during pregnancy.

In our center, gabapentin still would not be used as a first-line treatment for the management of anxiety or insomnia during pregnancy. But these new data still are reassuring for patients who come in, frequently with unplanned pregnancies. It is an important reminder to those of us taking care of patients during the pandemic to review use of contraception, because although data are unavailable specific to the period of the pandemic, what is clear is that, even prior to COVID-19, 50% of pregnancies in America were unplanned. Addressing issues of reliable use of contraception, particularly during the pandemic, is that much more important.

In this particular case, our clinician colleague in Virtual Rounds decided to continue gabapentin across pregnancy in the context of these reassuring data, but others may choose to discontinue or pursue some of the other treatment options noted above.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Since the start of the pandemic, we have been conducting an extra hour of Virtual Rounds at the Center for Women’s Mental Health. Virtual Rounds has been an opportunity to discuss cases around a spectrum of clinical management issues with respect to depression, bipolar disorder, and a spectrum of anxiety disorders like obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder. How to apply the calculus of risk-benefit decision-making around management of psychiatric disorder during pregnancy and the postpartum period has been the cornerstone of the work at our center for over 2 decades.

When we went virtual at our center in the early Spring, we decided to keep the format of our faculty rounds the way they have been for years and to sustain cohesiveness of our program during the pandemic. But we thought the needs of pregnant and postpartum women warranted being addressed in a context more specific to COVID-19, and also that reproductive psychiatrists and other clinicians could learn from each other about novel issues coming up for this group of patients during the pandemic. With that backdrop, Marlene Freeman, MD, and I founded “Virtual Rounds at the Center” to respond to queries from our colleagues across the country; we do this just after our own rounds on Wednesdays at 2:00 p.m.

As the pandemic has progressed, Virtual Rounds has blossomed into a virtual community on the Zoom platform, where social workers, psychologists, nurse prescribers, psychiatrists, and obstetricians discuss the needs of pregnant and postpartum women specific to COVID-19. Frequently, our discussions involve a review of the risks and benefits of treatment before, during, and after pregnancy.

Seemingly, week to week, more and more colleagues raise questions about the treatment of anxiety and insomnia during pregnancy and the postpartum period. I’ve spoken in previous columns about the enhanced use of telemedicine. Telemedicine not only facilitates efforts like Virtual Rounds and our ability to reach out to colleagues across the country and share cases, but also has allowed us to keep even closer tabs on the emotional well-being of our pregnant and postpartum women during COVID-19.

The question is not just about the effects of a medicine that a woman might take to treat anxiety or insomnia during pregnancy, but the experience of the pandemic per se, which we are measuring in multiple studies now using a variety of psychological instruments that patients complete. The pandemic is unequivocally taking a still unquantified toll on the mental health of Americans and potentially on the next generation to come.

Midcycle awakening during pregnancy

Complaints of insomnia and midcycle awakening during pregnancy are not new – it is the rule, rather than the exception for many pregnant women, particularly later in pregnancy. We have unequivocally seen a worsening of complaints of sleep disruption including insomnia and midcycle awakening during the pandemic that is greater than what we have seen previously. Both patients and colleagues have asked us the safest ways to manage it. One of the first things we consider when we hear about insomnia is whether it is part of an underlying mood disorder. While we see primary insomnia clinically, it really is important to remember that insomnia can be part and parcel of an underlying mood disorder.

With that in mind, what are the options? During the pandemic, we’ve seen an increased use of digital cognitive behavioral therapy for insomnia (CBT-I) for patients who cannot initiate sleep, which has a very strong evidence base for effectiveness as a first-line intervention for many.

If a patient has an incomplete response to CBT-I, what might be pursued next? In our center, we have a low threshold for using low doses of benzodiazepines, such as lorazepam or clonazepam, because the majority of data do not support an increased risk of major congenital malformations even when used in the first trimester. It is quite common to see medicines such as newer nonbenzodiazepine sedative hypnotics such as Ambien CR (zolpidem) or Lunesta (eszopiclone) used by our colleagues in ob.gyn. The reproductive safety data on those medicines are particularly sparse, and they may have greater risk of cognitive side effects the next day, so we tend to avoid them.

Another sometimes-forgotten option to consider is using low doses of tricyclic antidepressants (i.e., 10-25 mg of nortriptyline at bedtime), with tricyclics having a 40-year history and at least one pooled analysis showing the absence of increased risk for major congenital malformations when used. This may be a very easy way of managing insomnia, with low-dose tricyclics having an anxiolytic effect as well.

Anxiety during pregnancy

The most common rise in symptoms during COVID-19 for women who are pregnant or post partum has been an increase in anxiety. Women present with a spectrum of concerns leading to anxiety symptoms in the context of the pandemic. Earlier on in the pandemic, concerns focused mostly on how to stay healthy, and how to mitigate risk and not catch SARS-CoV-2 during pregnancy, as well as the very complex issues that were playing out in real time as hospital systems were figuring out how to manage pregnant women in labor and to keep both them and staff safe. Over time, anxiety has shifted to still staying safe during the pandemic and the potential impact of SARS-CoV-2 infection on pregnancy outcomes. The No. 1 concern is what the implications of COVID-19 disease are on mother and child. New mothers also are anxious about how they will practically navigate life with a newborn in the postpartum setting.

Early on in the pandemic, some hospital systems severely limited who was in the room with a woman during labor, potentially impeding the wishes of women during delivery who would have wanted their loved ones and/or a doula present, as an example. With enhanced testing available now, protocols have since relaxed in many hospitals to allow partners – but not a team – to remain in the hospital during the labor process. Still, the prospect of delivering during a pandemic is undoubtedly a source of anxiety for some women.

This sort of anxiety, particularly in patients with preexisting anxiety disorders, can be particularly challenging. Fortunately, there has been a rapid increase over the last several years of digital apps to mitigate anxiety. While many of them have not been systematically studied, the data on biobehavioral intervention for anxiety is enormous, and this should be used as first-line treatment for patients with mild to moderate symptoms; so many women would prefer to avoid pharmacological intervention during pregnancy, if possible, to avoid fetal drug exposure. For patients who meet criteria for frank anxiety disorder, other nonpharmacologic interventions such as CBT have been shown to be effective.

Frequently, we see women who are experiencing levels of anxiety where nonpharmacological interventions have an incomplete response, and colleagues have asked about the safest way to treat these patients. As has been discussed in multiple previous columns, selective serotonin reuptake inhibitors (SSRIs) should be thought of sooner rather than later, particularly with medicines with good reproductive safety data such as sertraline, citalopram, or fluoxetine.

We also reported over 15 years ago that at least 30%-40% of women presenting with histories of recurrent major depression at the beginning of pregnancy had comorbid anxiety disorders, and that the use of benzodiazepines in that population in addition to SSRIs was exceedingly common, with doses of approximately 0.5-1.5 mg of clonazepam or lorazepam being standard fare. Again, this is very appropriate treatment to mitigate anxiety symptoms because now have enough data as a field that support the existence of adverse outcomes associated with untreated anxiety during pregnancy in terms of both adverse obstetric and neonatal outcomes, higher rates of preterm birth, and other obstetric complications. Hence, managing anxiety during pregnancy should be considered like managing a toxic exposure – the same way that one would be concerned about anything else that a pregnant woman could be exposed to.

Lastly, although no atypical antipsychotic has been approved for the treatment of anxiety, its use off label is extremely common. More and more data support the absence of a signal of teratogenicity across the family of molecules including atypical antipsychotics. Beyond potential use of atypical antipsychotics, at Virtual Rounds last week, a colleague asked about the use of gabapentin in a patient who was diagnosed with substance use disorder and who had inadvertently conceived on gabapentin, which was being used to treat both anxiety and insomnia. We have typically avoided the use of gabapentin during pregnancy because prospective data have been limited to relatively small case series and one report, with a total of exposures in roughly the 300 range.

However, our colleagues at the Harvard School of Public Health have recently published an article that looked at the United States Medicaid Analytic eXtract (MAX) dataset, which has been used to publish other articles addressing atypical antipsychotics, SSRIs, lithium, and pharmacovigilance investigations among other important topics. In this study, the database was used to look specifically at 4,642 pregnancies with gabapentin exposure relative to 1,744,447 unexposed pregnancies, without a significant finding for increased risk for major congenital malformations.

The question of an increased risk of cardiac malformations and of increased risk for obstetric complications are difficult to untangle from anxiety and depression, as they also are associated with those same outcomes. With that said, the analysis is a welcome addition to our knowledge base for a medicine used more widely to treat symptoms such as anxiety and insomnia in the general population, with a question mark around where it may fit into the algorithm during pregnancy.

In our center, gabapentin still would not be used as a first-line treatment for the management of anxiety or insomnia during pregnancy. But these new data still are reassuring for patients who come in, frequently with unplanned pregnancies. It is an important reminder to those of us taking care of patients during the pandemic to review use of contraception, because although data are unavailable specific to the period of the pandemic, what is clear is that, even prior to COVID-19, 50% of pregnancies in America were unplanned. Addressing issues of reliable use of contraception, particularly during the pandemic, is that much more important.

In this particular case, our clinician colleague in Virtual Rounds decided to continue gabapentin across pregnancy in the context of these reassuring data, but others may choose to discontinue or pursue some of the other treatment options noted above.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.

“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.

Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.

However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.

In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).

If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.

In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.

Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.

“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.

Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.

He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.

Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.

“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.

Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.

However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.

In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).

If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.

In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.

Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.

“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.

Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.

He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.

Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.

“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.

Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.

However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.

In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).

If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.

In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.

Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.

“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.

Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.

He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.

Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.  

Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.  

This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
 

Ruxolitinib in chronic GvHD

“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.

In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.

One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.

“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”

There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).

“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.  
 

Transplants for older patients with MDS

Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.

New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.  

It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
 

Subcutaneous daratumumab

New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.

Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.

“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”  
 

Negative data with tranexamic acid

The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
 

‘Very exciting’ news about gene therapy

Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.

In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.

Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”

Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.

“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”

He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.

This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”

New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).

At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.

“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
 

Race and bloods cancers

ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).

It found that “self-reported race was the best indicator of survival,” noted Lee.

Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.

Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.

Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.

A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?” 
 

COVID-19 and blood disorders

Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.

An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.

“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.

“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
 

‘Fireside chat’ with Fauci

COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

“This will be kicking off our meeting on Saturday morning,” said Lee.

This article first appeared on Medscape.com.

For mid-career oncologist Tanya Wildes, MD, the pandemic was the last straw. In late September, she tweeted: “I have done the academically unfathomable: I am resigning my faculty position without another job lined up.”

She wasn’t burned out, she insisted. She loved her patients and her research. But she was also “100% confident” in her decision and “also 100% sad. This did not have to happen,” she lamented, asking not to disclose her workplace for fear of retribution.

Being a woman in medicine “is a hard life to start with,” Dr. Wildes said in an interview. “We all have that tenuous balance going on and the pandemic made everything just a little bit harder.”

She describes her prepandemic work-life balance as a “Jenga tower, with everything only just in place.” But she realized that the balance had tipped, when after a difficult clinic she felt emotionally wrung out. Her 11-year-old son had asked her to help him fly his model airplane. “I told him, ‘Honey, I can’t do it because if it crashes or gets stuck in a tree ... you’re going to be devastated and I have nothing left for you.’ “

This was a eureka moment, as “I realized, this is not who I want to be,” she said, holding back tears. “Seventy years from now my son is going to tell his grandchildren about the pandemic and I don’t want his memory of his mom to be that she couldn’t be there for him because she was too spent.”

When Dr. Wildes shared her story on Twitter, other female oncologists and physicians responded that they too have felt they’re under increased pressure this year, with the extra stress of the pandemic leading others to quit as well.

The trend of doctors leaving medicine has been noticeable. A July survey from the Physicians Foundation found that roughly 16,000 medical practices had already closed during the pandemic, with another 8,000 predicted to close within the next year.

“Similar patterns” were evident in another analysis by the Larry A. Green Center and the Primary Care Collaborative, as reported in The New York Times. In that survey, nearly one-fifth of primary care clinicians said “someone in their practice plans to retire early or has already retired because of COVID-19,” and 15% say “someone has left or plans to leave the practice.” About half said their mental exhaustion was at an all-time high, the survey found.

“COVID-19 is a burden, and that added burden has tipped people over the edge of many things,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital, Boston, and former president of the American Society of Clinical Oncology.

“It has illustrated that we do have a lot of people who are working kind of on the edge of not being able to handle everything,” she said.

While many in medicine are struggling, the pandemic seems to be pushing more women to leave, highlighting longtime gender disparities and increased caregiving burdens. And their absence may be felt for years to come.

Firm numbers are hard to come by, said Julie Silver, MD, associate professor, associate chair, and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston, and an expert in gender equity in medicine. But she sees some troubling trends.

“There are many indications that women are leaving medicine in disproportionately high numbers,” Dr. Silver said in an interview. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

A survey of 1,809 women conducted in mid-April with the Physician Moms Facebook Group and accepted for online publication by the American Journal of Psychiatry found that 41% scored over the cutoff points for moderate or severe anxiety, with 46% meeting these criteria among front-line workers.

“It’s really important for society to recognize the extraordinary impact this pandemic is having on physician mothers, as there will be profound ripple effects on the ability of this key segment of the health care workforce to serve others if we do not address this problem urgently,” co-senior author Reshma Jagsi, MD, DPhil, a radiation oncologist at the University of Michigan, Ann Arbor, said in an interview.

Women weighed in on Twitter, in response to Dr. Silver’s tweet to #WomenInMedicine: “If you are thinking of leaving #medicine & need a reason to stay: we value you & need you.”

In reply, Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado at Denver, Aurora, said via Twitter, “I’ve had lots of conversations with women considering leaving medicine.”

“I have thought about leaving many times. I love what I do, but medicine can be an unkind world at times,” responded Valerie Fitzhugh MD, associate professor and pathologist at New Jersey Medical School, Newark.

“Too late. Left at the end of July and it was the best decision ever,” wrote Michelle Gordon, DO, who was previously a board-certified general surgeon at Northern Westchester Surgical Associates in Putnam Valley, N.Y.


 

Prepandemic disparities accentuated

The pandemic “has merely accentuated – or made more apparent – some of the longstanding issues and struggles of women in oncology, women in medicine, women in academia,” said Sarah Holstein, MD, PhD, another mid-career oncologist and associate professor at the University of Nebraska Medical Center, Omaha.

“There are disparities in first-author/last-author publications, disparities in being asked to give speaking engagements, disparities in leadership,” Dr. Holstein said in an interview. “And then ... put on top of that the various surges with the pandemic where you are being asked to do clinical responsibilities you don’t normally do, perhaps some things you haven’t done since your training 10 or 20 years ago.”

This is backed up with data: There is already a “robust” body of prepandemic literature demonstrating pay gaps for female physicians and scientists, noted Dr. Silver, who founded the Her Time Is Now campaign for gender equity in medicine and runs a women’s leadership course at Harvard.

In addition, female physicians are more likely to be involved in “nonpromotable” work, group projects and educator roles that are often underappreciated and undercompensated, she said.

Writing recently in a blog post for the BMJ, Dr. Silver and colleagues predict that as a result of the pandemic, female physicians will “face disadvantages from unconscious bias in decisions about whose pay should be cut, whose operating schedules should take priority when resources are limited, and whose contributions merit retention ... The ground that women lose now will likely have a profound effect for many years to come, perhaps putting them at a disadvantage for the rest of their careers.”

There is already evidence of reduced publishing by female scientists during the pandemic, something that “could undermine the careers of an entire generation of women scholars,” noted Caitlyn Collins, PhD, assistant professor of sociology at Washington University in St. Louis.

“Science needs to address the culture of overwork,” Dr. Collins said in an interview. “Parents and other caregivers deserve support. The stress and ‘overwhelm’ they feel is not inevitable. A more fair, just, and humane approach to combining work and family is possible – what we need is the political will to pass better policies and a massive shift in our cultural understandings about how work should fit into family life, not the other way around.”

Lack of support for “vulnerable scientists,” particularly “junior scientists who are parents, women, or minorities” could lead to “severe attrition in cancer research in the coming years,” Cullen Taniguchi, MD, PhD, a radiation oncologist and associate professor at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, warned in a recent letter to the journal Cancer Cell.

“The biggest worries of attrition will come from young faculty who started just before or after the pandemic,” Dr. Taniguchi said in an interview. “The first year in an academic setting is incredibly challenging but also important for establishing research efforts and building networks of colleagues to collaborate with. While completely necessary, the restrictions put in place during the pandemic made doing these things even more difficult.”
 

Another stressor: Caregiving at home

Another reason female physicians may be marginalized during the pandemic is that they are more often the primary caregivers at home.

“Anyone who is a caregiver, be it to kids, parents, or spouses, can relate to the challenges brought [on] by the pandemic,” said Ishwaria Subbiah, MD, a palliative care physician and medical oncologist at MD Anderson.

“Most of us work toward meeting our responsibilities by engaging a network of support, whether it’s home care workers, center-based or at-home child care, schools, or activities outside of school. The pandemic led to a level of disruption that brought most (if not all) of those responsibilities onto the caregivers themselves,” she said in an interview.

As the mother of an adult son with severe epilepsy, Dr. Bertagnolli has certainly experienced the challenges of parenting during the pandemic. “Our son is now 24 but he is handicapped, and lives with us. The care issues we have to deal with as professionals have been enormously magnified by COVID,” she said.

But she cautions against making gender distinctions when it comes to caregiving. “Has it fallen on the women? Well, this kind of stuff generally falls on the women, but I am certain it has fallen on an awful lot of men as well, because I think the world is changing that way, so it’s fallen on all of us.”

There is no question that female oncologists are bearing the brunt, both at work and at home, contended Dr. Taniguchi. “Absolutely. I have seen this first-hand,” he said.

“If it was difficult for women, underrepresented minorities, and junior faculty to find a voice in the room prepandemic, I think it can be harder in the times of virtual meetings when it is difficult to engage audiences,” he said. 

Dr. Holstein said she is lucky to be well-supported at her institution, with both a female chief of hematology/oncology and a female chair of internal medicine, but still, she worries about the long-term consequences of the pandemic on the gender landscape of medicine.

“If you’re having to put aside research projects because you have extra responsibilities – again because women just tend to have a lot of other things going on – that might not be a big deal for 3 months, 6 months, but this is going to be a year or 2 years before ‘normal’ comes back,” she says. “One to two years of underpublishing or not getting the grants could be career killers for women in academic oncology.”
 

Cancer COVID-19 combo

As Dr. Wildes completed her final weeks of seeing cancer patients, she received an outpouring of support, which she says convinced her of the shared experience of all doctors, and especially female doctors, during the pandemic. But even more specifically, she feels that she has tapped into the unique burden shouldered by oncologists during this time.

“It’s intimidating being an oncologist; we are literally giving people poison for a living. Then throw into it a pandemic where early in March we had so little data. I was helping my patients make decisions about their cancer care based on a case series of four patients in China. The burden of those conversations is something I never want to have to live through again,” she said.

“Oncology is a particularly intense subspecialty within medicine,” agreed Dr. Subbiah. “The people we care for have received a life-altering and potentially life-limiting diagnosis. Coupled with that, the COVID-19 pandemic has brought an unprecedented cloud of uncertainty ... Whether the patients can see it overtly or not, oncologists carry the weight of this worry with them for not just one but all of their patients.”

Dr. Wildes said she plans to return to academic medicine and clinical care “in time,” but for now, the gap that she and others like her leave is troubling to those who have stayed on.

“We need these women in medicine,” said Dr. Holstein. “We have data suggesting that women take more time with their patients than men, that patient outcomes are better if they have a female physician. But also for the generations coming up, we need the mid-career and senior women to be in place to mentor and guide and make sure we continue to increase women in leadership.”

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

For mid-career oncologist Tanya Wildes, MD, the pandemic was the last straw. In late September, she tweeted: “I have done the academically unfathomable: I am resigning my faculty position without another job lined up.”

She wasn’t burned out, she insisted. She loved her patients and her research. But she was also “100% confident” in her decision and “also 100% sad. This did not have to happen,” she lamented, asking not to disclose her workplace for fear of retribution.

Being a woman in medicine “is a hard life to start with,” Dr. Wildes said in an interview. “We all have that tenuous balance going on and the pandemic made everything just a little bit harder.”

She describes her prepandemic work-life balance as a “Jenga tower, with everything only just in place.” But she realized that the balance had tipped, when after a difficult clinic she felt emotionally wrung out. Her 11-year-old son had asked her to help him fly his model airplane. “I told him, ‘Honey, I can’t do it because if it crashes or gets stuck in a tree ... you’re going to be devastated and I have nothing left for you.’ “

This was a eureka moment, as “I realized, this is not who I want to be,” she said, holding back tears. “Seventy years from now my son is going to tell his grandchildren about the pandemic and I don’t want his memory of his mom to be that she couldn’t be there for him because she was too spent.”

When Dr. Wildes shared her story on Twitter, other female oncologists and physicians responded that they too have felt they’re under increased pressure this year, with the extra stress of the pandemic leading others to quit as well.

The trend of doctors leaving medicine has been noticeable. A July survey from the Physicians Foundation found that roughly 16,000 medical practices had already closed during the pandemic, with another 8,000 predicted to close within the next year.

“Similar patterns” were evident in another analysis by the Larry A. Green Center and the Primary Care Collaborative, as reported in The New York Times. In that survey, nearly one-fifth of primary care clinicians said “someone in their practice plans to retire early or has already retired because of COVID-19,” and 15% say “someone has left or plans to leave the practice.” About half said their mental exhaustion was at an all-time high, the survey found.

“COVID-19 is a burden, and that added burden has tipped people over the edge of many things,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital, Boston, and former president of the American Society of Clinical Oncology.

“It has illustrated that we do have a lot of people who are working kind of on the edge of not being able to handle everything,” she said.

While many in medicine are struggling, the pandemic seems to be pushing more women to leave, highlighting longtime gender disparities and increased caregiving burdens. And their absence may be felt for years to come.

Firm numbers are hard to come by, said Julie Silver, MD, associate professor, associate chair, and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston, and an expert in gender equity in medicine. But she sees some troubling trends.

“There are many indications that women are leaving medicine in disproportionately high numbers,” Dr. Silver said in an interview. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

A survey of 1,809 women conducted in mid-April with the Physician Moms Facebook Group and accepted for online publication by the American Journal of Psychiatry found that 41% scored over the cutoff points for moderate or severe anxiety, with 46% meeting these criteria among front-line workers.

“It’s really important for society to recognize the extraordinary impact this pandemic is having on physician mothers, as there will be profound ripple effects on the ability of this key segment of the health care workforce to serve others if we do not address this problem urgently,” co-senior author Reshma Jagsi, MD, DPhil, a radiation oncologist at the University of Michigan, Ann Arbor, said in an interview.

Women weighed in on Twitter, in response to Dr. Silver’s tweet to #WomenInMedicine: “If you are thinking of leaving #medicine & need a reason to stay: we value you & need you.”

In reply, Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado at Denver, Aurora, said via Twitter, “I’ve had lots of conversations with women considering leaving medicine.”

“I have thought about leaving many times. I love what I do, but medicine can be an unkind world at times,” responded Valerie Fitzhugh MD, associate professor and pathologist at New Jersey Medical School, Newark.

“Too late. Left at the end of July and it was the best decision ever,” wrote Michelle Gordon, DO, who was previously a board-certified general surgeon at Northern Westchester Surgical Associates in Putnam Valley, N.Y.


 

Prepandemic disparities accentuated

The pandemic “has merely accentuated – or made more apparent – some of the longstanding issues and struggles of women in oncology, women in medicine, women in academia,” said Sarah Holstein, MD, PhD, another mid-career oncologist and associate professor at the University of Nebraska Medical Center, Omaha.

“There are disparities in first-author/last-author publications, disparities in being asked to give speaking engagements, disparities in leadership,” Dr. Holstein said in an interview. “And then ... put on top of that the various surges with the pandemic where you are being asked to do clinical responsibilities you don’t normally do, perhaps some things you haven’t done since your training 10 or 20 years ago.”

This is backed up with data: There is already a “robust” body of prepandemic literature demonstrating pay gaps for female physicians and scientists, noted Dr. Silver, who founded the Her Time Is Now campaign for gender equity in medicine and runs a women’s leadership course at Harvard.

In addition, female physicians are more likely to be involved in “nonpromotable” work, group projects and educator roles that are often underappreciated and undercompensated, she said.

Writing recently in a blog post for the BMJ, Dr. Silver and colleagues predict that as a result of the pandemic, female physicians will “face disadvantages from unconscious bias in decisions about whose pay should be cut, whose operating schedules should take priority when resources are limited, and whose contributions merit retention ... The ground that women lose now will likely have a profound effect for many years to come, perhaps putting them at a disadvantage for the rest of their careers.”

There is already evidence of reduced publishing by female scientists during the pandemic, something that “could undermine the careers of an entire generation of women scholars,” noted Caitlyn Collins, PhD, assistant professor of sociology at Washington University in St. Louis.

“Science needs to address the culture of overwork,” Dr. Collins said in an interview. “Parents and other caregivers deserve support. The stress and ‘overwhelm’ they feel is not inevitable. A more fair, just, and humane approach to combining work and family is possible – what we need is the political will to pass better policies and a massive shift in our cultural understandings about how work should fit into family life, not the other way around.”

Lack of support for “vulnerable scientists,” particularly “junior scientists who are parents, women, or minorities” could lead to “severe attrition in cancer research in the coming years,” Cullen Taniguchi, MD, PhD, a radiation oncologist and associate professor at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, warned in a recent letter to the journal Cancer Cell.

“The biggest worries of attrition will come from young faculty who started just before or after the pandemic,” Dr. Taniguchi said in an interview. “The first year in an academic setting is incredibly challenging but also important for establishing research efforts and building networks of colleagues to collaborate with. While completely necessary, the restrictions put in place during the pandemic made doing these things even more difficult.”
 

Another stressor: Caregiving at home

Another reason female physicians may be marginalized during the pandemic is that they are more often the primary caregivers at home.

“Anyone who is a caregiver, be it to kids, parents, or spouses, can relate to the challenges brought [on] by the pandemic,” said Ishwaria Subbiah, MD, a palliative care physician and medical oncologist at MD Anderson.

“Most of us work toward meeting our responsibilities by engaging a network of support, whether it’s home care workers, center-based or at-home child care, schools, or activities outside of school. The pandemic led to a level of disruption that brought most (if not all) of those responsibilities onto the caregivers themselves,” she said in an interview.

As the mother of an adult son with severe epilepsy, Dr. Bertagnolli has certainly experienced the challenges of parenting during the pandemic. “Our son is now 24 but he is handicapped, and lives with us. The care issues we have to deal with as professionals have been enormously magnified by COVID,” she said.

But she cautions against making gender distinctions when it comes to caregiving. “Has it fallen on the women? Well, this kind of stuff generally falls on the women, but I am certain it has fallen on an awful lot of men as well, because I think the world is changing that way, so it’s fallen on all of us.”

There is no question that female oncologists are bearing the brunt, both at work and at home, contended Dr. Taniguchi. “Absolutely. I have seen this first-hand,” he said.

“If it was difficult for women, underrepresented minorities, and junior faculty to find a voice in the room prepandemic, I think it can be harder in the times of virtual meetings when it is difficult to engage audiences,” he said. 

Dr. Holstein said she is lucky to be well-supported at her institution, with both a female chief of hematology/oncology and a female chair of internal medicine, but still, she worries about the long-term consequences of the pandemic on the gender landscape of medicine.

“If you’re having to put aside research projects because you have extra responsibilities – again because women just tend to have a lot of other things going on – that might not be a big deal for 3 months, 6 months, but this is going to be a year or 2 years before ‘normal’ comes back,” she says. “One to two years of underpublishing or not getting the grants could be career killers for women in academic oncology.”
 

Cancer COVID-19 combo

As Dr. Wildes completed her final weeks of seeing cancer patients, she received an outpouring of support, which she says convinced her of the shared experience of all doctors, and especially female doctors, during the pandemic. But even more specifically, she feels that she has tapped into the unique burden shouldered by oncologists during this time.

“It’s intimidating being an oncologist; we are literally giving people poison for a living. Then throw into it a pandemic where early in March we had so little data. I was helping my patients make decisions about their cancer care based on a case series of four patients in China. The burden of those conversations is something I never want to have to live through again,” she said.

“Oncology is a particularly intense subspecialty within medicine,” agreed Dr. Subbiah. “The people we care for have received a life-altering and potentially life-limiting diagnosis. Coupled with that, the COVID-19 pandemic has brought an unprecedented cloud of uncertainty ... Whether the patients can see it overtly or not, oncologists carry the weight of this worry with them for not just one but all of their patients.”

Dr. Wildes said she plans to return to academic medicine and clinical care “in time,” but for now, the gap that she and others like her leave is troubling to those who have stayed on.

“We need these women in medicine,” said Dr. Holstein. “We have data suggesting that women take more time with their patients than men, that patient outcomes are better if they have a female physician. But also for the generations coming up, we need the mid-career and senior women to be in place to mentor and guide and make sure we continue to increase women in leadership.”

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

For mid-career oncologist Tanya Wildes, MD, the pandemic was the last straw. In late September, she tweeted: “I have done the academically unfathomable: I am resigning my faculty position without another job lined up.”

She wasn’t burned out, she insisted. She loved her patients and her research. But she was also “100% confident” in her decision and “also 100% sad. This did not have to happen,” she lamented, asking not to disclose her workplace for fear of retribution.

Being a woman in medicine “is a hard life to start with,” Dr. Wildes said in an interview. “We all have that tenuous balance going on and the pandemic made everything just a little bit harder.”

She describes her prepandemic work-life balance as a “Jenga tower, with everything only just in place.” But she realized that the balance had tipped, when after a difficult clinic she felt emotionally wrung out. Her 11-year-old son had asked her to help him fly his model airplane. “I told him, ‘Honey, I can’t do it because if it crashes or gets stuck in a tree ... you’re going to be devastated and I have nothing left for you.’ “

This was a eureka moment, as “I realized, this is not who I want to be,” she said, holding back tears. “Seventy years from now my son is going to tell his grandchildren about the pandemic and I don’t want his memory of his mom to be that she couldn’t be there for him because she was too spent.”

When Dr. Wildes shared her story on Twitter, other female oncologists and physicians responded that they too have felt they’re under increased pressure this year, with the extra stress of the pandemic leading others to quit as well.

The trend of doctors leaving medicine has been noticeable. A July survey from the Physicians Foundation found that roughly 16,000 medical practices had already closed during the pandemic, with another 8,000 predicted to close within the next year.

“Similar patterns” were evident in another analysis by the Larry A. Green Center and the Primary Care Collaborative, as reported in The New York Times. In that survey, nearly one-fifth of primary care clinicians said “someone in their practice plans to retire early or has already retired because of COVID-19,” and 15% say “someone has left or plans to leave the practice.” About half said their mental exhaustion was at an all-time high, the survey found.

“COVID-19 is a burden, and that added burden has tipped people over the edge of many things,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital, Boston, and former president of the American Society of Clinical Oncology.

“It has illustrated that we do have a lot of people who are working kind of on the edge of not being able to handle everything,” she said.

While many in medicine are struggling, the pandemic seems to be pushing more women to leave, highlighting longtime gender disparities and increased caregiving burdens. And their absence may be felt for years to come.

Firm numbers are hard to come by, said Julie Silver, MD, associate professor, associate chair, and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston, and an expert in gender equity in medicine. But she sees some troubling trends.

“There are many indications that women are leaving medicine in disproportionately high numbers,” Dr. Silver said in an interview. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

A survey of 1,809 women conducted in mid-April with the Physician Moms Facebook Group and accepted for online publication by the American Journal of Psychiatry found that 41% scored over the cutoff points for moderate or severe anxiety, with 46% meeting these criteria among front-line workers.

“It’s really important for society to recognize the extraordinary impact this pandemic is having on physician mothers, as there will be profound ripple effects on the ability of this key segment of the health care workforce to serve others if we do not address this problem urgently,” co-senior author Reshma Jagsi, MD, DPhil, a radiation oncologist at the University of Michigan, Ann Arbor, said in an interview.

Women weighed in on Twitter, in response to Dr. Silver’s tweet to #WomenInMedicine: “If you are thinking of leaving #medicine & need a reason to stay: we value you & need you.”

In reply, Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado at Denver, Aurora, said via Twitter, “I’ve had lots of conversations with women considering leaving medicine.”

“I have thought about leaving many times. I love what I do, but medicine can be an unkind world at times,” responded Valerie Fitzhugh MD, associate professor and pathologist at New Jersey Medical School, Newark.

“Too late. Left at the end of July and it was the best decision ever,” wrote Michelle Gordon, DO, who was previously a board-certified general surgeon at Northern Westchester Surgical Associates in Putnam Valley, N.Y.


 

Prepandemic disparities accentuated

The pandemic “has merely accentuated – or made more apparent – some of the longstanding issues and struggles of women in oncology, women in medicine, women in academia,” said Sarah Holstein, MD, PhD, another mid-career oncologist and associate professor at the University of Nebraska Medical Center, Omaha.

“There are disparities in first-author/last-author publications, disparities in being asked to give speaking engagements, disparities in leadership,” Dr. Holstein said in an interview. “And then ... put on top of that the various surges with the pandemic where you are being asked to do clinical responsibilities you don’t normally do, perhaps some things you haven’t done since your training 10 or 20 years ago.”

This is backed up with data: There is already a “robust” body of prepandemic literature demonstrating pay gaps for female physicians and scientists, noted Dr. Silver, who founded the Her Time Is Now campaign for gender equity in medicine and runs a women’s leadership course at Harvard.

In addition, female physicians are more likely to be involved in “nonpromotable” work, group projects and educator roles that are often underappreciated and undercompensated, she said.

Writing recently in a blog post for the BMJ, Dr. Silver and colleagues predict that as a result of the pandemic, female physicians will “face disadvantages from unconscious bias in decisions about whose pay should be cut, whose operating schedules should take priority when resources are limited, and whose contributions merit retention ... The ground that women lose now will likely have a profound effect for many years to come, perhaps putting them at a disadvantage for the rest of their careers.”

There is already evidence of reduced publishing by female scientists during the pandemic, something that “could undermine the careers of an entire generation of women scholars,” noted Caitlyn Collins, PhD, assistant professor of sociology at Washington University in St. Louis.

“Science needs to address the culture of overwork,” Dr. Collins said in an interview. “Parents and other caregivers deserve support. The stress and ‘overwhelm’ they feel is not inevitable. A more fair, just, and humane approach to combining work and family is possible – what we need is the political will to pass better policies and a massive shift in our cultural understandings about how work should fit into family life, not the other way around.”

Lack of support for “vulnerable scientists,” particularly “junior scientists who are parents, women, or minorities” could lead to “severe attrition in cancer research in the coming years,” Cullen Taniguchi, MD, PhD, a radiation oncologist and associate professor at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, warned in a recent letter to the journal Cancer Cell.

“The biggest worries of attrition will come from young faculty who started just before or after the pandemic,” Dr. Taniguchi said in an interview. “The first year in an academic setting is incredibly challenging but also important for establishing research efforts and building networks of colleagues to collaborate with. While completely necessary, the restrictions put in place during the pandemic made doing these things even more difficult.”
 

Another stressor: Caregiving at home

Another reason female physicians may be marginalized during the pandemic is that they are more often the primary caregivers at home.

“Anyone who is a caregiver, be it to kids, parents, or spouses, can relate to the challenges brought [on] by the pandemic,” said Ishwaria Subbiah, MD, a palliative care physician and medical oncologist at MD Anderson.

“Most of us work toward meeting our responsibilities by engaging a network of support, whether it’s home care workers, center-based or at-home child care, schools, or activities outside of school. The pandemic led to a level of disruption that brought most (if not all) of those responsibilities onto the caregivers themselves,” she said in an interview.

As the mother of an adult son with severe epilepsy, Dr. Bertagnolli has certainly experienced the challenges of parenting during the pandemic. “Our son is now 24 but he is handicapped, and lives with us. The care issues we have to deal with as professionals have been enormously magnified by COVID,” she said.

But she cautions against making gender distinctions when it comes to caregiving. “Has it fallen on the women? Well, this kind of stuff generally falls on the women, but I am certain it has fallen on an awful lot of men as well, because I think the world is changing that way, so it’s fallen on all of us.”

There is no question that female oncologists are bearing the brunt, both at work and at home, contended Dr. Taniguchi. “Absolutely. I have seen this first-hand,” he said.

“If it was difficult for women, underrepresented minorities, and junior faculty to find a voice in the room prepandemic, I think it can be harder in the times of virtual meetings when it is difficult to engage audiences,” he said. 

Dr. Holstein said she is lucky to be well-supported at her institution, with both a female chief of hematology/oncology and a female chair of internal medicine, but still, she worries about the long-term consequences of the pandemic on the gender landscape of medicine.

“If you’re having to put aside research projects because you have extra responsibilities – again because women just tend to have a lot of other things going on – that might not be a big deal for 3 months, 6 months, but this is going to be a year or 2 years before ‘normal’ comes back,” she says. “One to two years of underpublishing or not getting the grants could be career killers for women in academic oncology.”
 

Cancer COVID-19 combo

As Dr. Wildes completed her final weeks of seeing cancer patients, she received an outpouring of support, which she says convinced her of the shared experience of all doctors, and especially female doctors, during the pandemic. But even more specifically, she feels that she has tapped into the unique burden shouldered by oncologists during this time.

“It’s intimidating being an oncologist; we are literally giving people poison for a living. Then throw into it a pandemic where early in March we had so little data. I was helping my patients make decisions about their cancer care based on a case series of four patients in China. The burden of those conversations is something I never want to have to live through again,” she said.

“Oncology is a particularly intense subspecialty within medicine,” agreed Dr. Subbiah. “The people we care for have received a life-altering and potentially life-limiting diagnosis. Coupled with that, the COVID-19 pandemic has brought an unprecedented cloud of uncertainty ... Whether the patients can see it overtly or not, oncologists carry the weight of this worry with them for not just one but all of their patients.”

Dr. Wildes said she plans to return to academic medicine and clinical care “in time,” but for now, the gap that she and others like her leave is troubling to those who have stayed on.

“We need these women in medicine,” said Dr. Holstein. “We have data suggesting that women take more time with their patients than men, that patient outcomes are better if they have a female physician. But also for the generations coming up, we need the mid-career and senior women to be in place to mentor and guide and make sure we continue to increase women in leadership.”

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

The numbers tell the story:

110,066 veterans diagnosed with COVID-19 as of November 30;

879,457 veterans and employees tested for COVID-19 as of November 6;

14,168 veterans admitted to a US Department of Veterans Affairs (VA) medical center for COVID-19 care;

1,525% increase in telehealth visits;

59,095 new staff hired to meet surge in demand for COVID-19 care;

75 completed Fourth Mission assignments; and

> 2,000 VA employees helping to support nonveteran patients and non-VA health care systems.

But those numbers are just some of the data in the COVID-19 Response Report, which the VA recently released. The report offers “an extensive look at VA’s complex COVID-19 response,” including how it prepared for the pandemic, the initial response, and key COVID-19 policies and directives.

The report was compiled from more than 90 interviews with health care leaders and stakeholders, along with documents and data pertaining to the Veterans Integrated Service Networks. The interviews were designed to “keep discussion at a strategic level.”

Meeting the crisis mandated that the Veterans Health Administration (VHA) act “with unity of effort and agility,” the authors note, across 18 networks with 170 medical centers. Not only is the VA called on to serve veterans, but its “Fourth Mission” explicitly calls on the VA to “improve the Nation’s preparedness for response to war, terrorism, national emergencies, and natural disasters.” But the VHA possessed some major assets, they add, including a nationwide capacity for inpatient health care, “considerable experience” generating and managing response to regional and local public health emergencies, and strong clinical processes focused on evidence-based guidelines. However, “[w]ithout national analytics of data from outbreaks in other nations, and without a national plan addressing the VHA role, forecasting demand for VHA inpatient services under the Fourth Mission required assumptions with a high degree of uncertainty.”

VHA planners adapted the existing High Consequence Infections Base Plan to COVID-19 and then developed the COVID-19 Response Plan as an annex to that. They released their plan to the public in the interest of a coordinated national response—although not all states were aware of VHA’s important safety-net capabilities. Despite that, the report says, during the pandemic, the mission assignments under the VA’s Fourth Mission have grown to the greatest scale and scope in the VA’s history.

“[H]ealth care in the United States will never be the same,” said Richard Stone, MD, VHA Executive in Charge, in his foreword to the report. Much of what we now consider routine, he said, such as parking lot screenings, digital questionnaires and rapid testing “were revolutionary and challenging to implement” when the pandemic began. “While we are certainly not perfect, we are a learning organization and seek to always find ways to improve.”

Identifying root causes for complex process problems is essential to improvement, the report authors say, and require “new knowledge.” To that end, the VA also has played a critical role in COVID-19–related research, participating in more than 90 and leading 28 multiple-site COVID-19 research studies, including research on 3D-printed respirator masks and convalescent plasma treatment.

The VA’s pandemic response has been “robust and far-reaching,” said VA Secretary Robert Wilkie. The report, he adds, “reflects VA’s agility throughout the pandemic to adapt based on lessons learned.”

The numbers tell the story:

110,066 veterans diagnosed with COVID-19 as of November 30;

879,457 veterans and employees tested for COVID-19 as of November 6;

14,168 veterans admitted to a US Department of Veterans Affairs (VA) medical center for COVID-19 care;

1,525% increase in telehealth visits;

59,095 new staff hired to meet surge in demand for COVID-19 care;

75 completed Fourth Mission assignments; and

> 2,000 VA employees helping to support nonveteran patients and non-VA health care systems.

But those numbers are just some of the data in the COVID-19 Response Report, which the VA recently released. The report offers “an extensive look at VA’s complex COVID-19 response,” including how it prepared for the pandemic, the initial response, and key COVID-19 policies and directives.

The report was compiled from more than 90 interviews with health care leaders and stakeholders, along with documents and data pertaining to the Veterans Integrated Service Networks. The interviews were designed to “keep discussion at a strategic level.”

Meeting the crisis mandated that the Veterans Health Administration (VHA) act “with unity of effort and agility,” the authors note, across 18 networks with 170 medical centers. Not only is the VA called on to serve veterans, but its “Fourth Mission” explicitly calls on the VA to “improve the Nation’s preparedness for response to war, terrorism, national emergencies, and natural disasters.” But the VHA possessed some major assets, they add, including a nationwide capacity for inpatient health care, “considerable experience” generating and managing response to regional and local public health emergencies, and strong clinical processes focused on evidence-based guidelines. However, “[w]ithout national analytics of data from outbreaks in other nations, and without a national plan addressing the VHA role, forecasting demand for VHA inpatient services under the Fourth Mission required assumptions with a high degree of uncertainty.”

VHA planners adapted the existing High Consequence Infections Base Plan to COVID-19 and then developed the COVID-19 Response Plan as an annex to that. They released their plan to the public in the interest of a coordinated national response—although not all states were aware of VHA’s important safety-net capabilities. Despite that, the report says, during the pandemic, the mission assignments under the VA’s Fourth Mission have grown to the greatest scale and scope in the VA’s history.

“[H]ealth care in the United States will never be the same,” said Richard Stone, MD, VHA Executive in Charge, in his foreword to the report. Much of what we now consider routine, he said, such as parking lot screenings, digital questionnaires and rapid testing “were revolutionary and challenging to implement” when the pandemic began. “While we are certainly not perfect, we are a learning organization and seek to always find ways to improve.”

Identifying root causes for complex process problems is essential to improvement, the report authors say, and require “new knowledge.” To that end, the VA also has played a critical role in COVID-19–related research, participating in more than 90 and leading 28 multiple-site COVID-19 research studies, including research on 3D-printed respirator masks and convalescent plasma treatment.

The VA’s pandemic response has been “robust and far-reaching,” said VA Secretary Robert Wilkie. The report, he adds, “reflects VA’s agility throughout the pandemic to adapt based on lessons learned.”

The numbers tell the story:

110,066 veterans diagnosed with COVID-19 as of November 30;

879,457 veterans and employees tested for COVID-19 as of November 6;

14,168 veterans admitted to a US Department of Veterans Affairs (VA) medical center for COVID-19 care;

1,525% increase in telehealth visits;

59,095 new staff hired to meet surge in demand for COVID-19 care;

75 completed Fourth Mission assignments; and

> 2,000 VA employees helping to support nonveteran patients and non-VA health care systems.

But those numbers are just some of the data in the COVID-19 Response Report, which the VA recently released. The report offers “an extensive look at VA’s complex COVID-19 response,” including how it prepared for the pandemic, the initial response, and key COVID-19 policies and directives.

The report was compiled from more than 90 interviews with health care leaders and stakeholders, along with documents and data pertaining to the Veterans Integrated Service Networks. The interviews were designed to “keep discussion at a strategic level.”

Meeting the crisis mandated that the Veterans Health Administration (VHA) act “with unity of effort and agility,” the authors note, across 18 networks with 170 medical centers. Not only is the VA called on to serve veterans, but its “Fourth Mission” explicitly calls on the VA to “improve the Nation’s preparedness for response to war, terrorism, national emergencies, and natural disasters.” But the VHA possessed some major assets, they add, including a nationwide capacity for inpatient health care, “considerable experience” generating and managing response to regional and local public health emergencies, and strong clinical processes focused on evidence-based guidelines. However, “[w]ithout national analytics of data from outbreaks in other nations, and without a national plan addressing the VHA role, forecasting demand for VHA inpatient services under the Fourth Mission required assumptions with a high degree of uncertainty.”

VHA planners adapted the existing High Consequence Infections Base Plan to COVID-19 and then developed the COVID-19 Response Plan as an annex to that. They released their plan to the public in the interest of a coordinated national response—although not all states were aware of VHA’s important safety-net capabilities. Despite that, the report says, during the pandemic, the mission assignments under the VA’s Fourth Mission have grown to the greatest scale and scope in the VA’s history.

“[H]ealth care in the United States will never be the same,” said Richard Stone, MD, VHA Executive in Charge, in his foreword to the report. Much of what we now consider routine, he said, such as parking lot screenings, digital questionnaires and rapid testing “were revolutionary and challenging to implement” when the pandemic began. “While we are certainly not perfect, we are a learning organization and seek to always find ways to improve.”

Identifying root causes for complex process problems is essential to improvement, the report authors say, and require “new knowledge.” To that end, the VA also has played a critical role in COVID-19–related research, participating in more than 90 and leading 28 multiple-site COVID-19 research studies, including research on 3D-printed respirator masks and convalescent plasma treatment.

The VA’s pandemic response has been “robust and far-reaching,” said VA Secretary Robert Wilkie. The report, he adds, “reflects VA’s agility throughout the pandemic to adapt based on lessons learned.”